In the water/triethanolamine/ethanol system, TiCl4 aqueous solution is used as the precursor to regulate the conversion rate of TiCl4 by changing the reaction temperature, water volume, pH value, and ethanol amount. The experiment uses a single-factor method to investigate the dynamic relationship between Ti4+ concentration and time under various factors, thereby achieving controllable TiO2 production. The experimental results showed that under a single factor, the conversion rate showed a trend of first steep and then slow growth within 180 min. After 180 min, the conversion rate tended to stabilize. Considering various factors, it was found that VTiCl4:VC6H15NO3:VH2O:VC2H5OH = 1:6:15:30, pH = 7, reaction time at room temperature was 4 h, and the hydrolysis effect was good. The final conversion rate was 90.46%, and the hydrolysis reaction conforms to the first-order reaction equation. Kinetic parameters: pre-factor (A) = 0.107, activation energy (Ea) = 4488.65 J mol-1. watertriethanolamineethanol triethanolamine system TiCl volume value amount singlefactor factor Ti4 Ti factors TiO production 18 min stabilize VTiCl4VC6H15NO3VH2OVC2H5OH VTiClVCHNOVHOVCHOH VTiCl4 VC6H15NO3 VH2O VC2H5OH VTiCl VC H NO VH O OH 161530, 161530 1 6 15 30, 30 1:6:15:30 7 h good 9046 90 46 90.46% firstorder order equation parameters prefactor pre A (A 0107 0 107 0.107 Ea (Ea 448865 4488 65 4488.6 mol1. mol1 mol 1. mol-1 OVC VCHNO VC6H15NO VHO VCHOH 16153 3 1:6:15:3 904 9 90.46 010 10 0.10 44886 448 4488. mol- 1615 1:6:15: 90.4 01 0.1 44 161 1:6:15 90. 0. 16 1:6:1 1:6: 1:6 1:

SUMMARY: Hypoxic preconditioning is known to induce neuroprotection, but its effects and pathways in chronic brain pathology still unknown. The aim was to establish an involvement of a7 subunit of nicotinic acetylcholine receptors (a7nAchRs), and sirtuins of 1 (SIRT1) and 3 (SIRT3) types in the effects of hypoxic hypobaric preconditioning on brain damage in mice with chronic cerebral hypoperfusion caused by the left common carotid artery occlusion. The male C57/6j (C57, wild type) and a7nAchRs(-/-) mice were divided to six experimental groups (10 mice per group): sham-operated C57, C57 with chronic cerebral hypoperfusion, C57 with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion, sham-operated a7nAchRs(-/-) mice, a7nAchRs(-/-) with chronic cerebral hypoperfusion, a7nAchRs(-/-) with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion. For preconditioning, mice were exposed to hypoxia by “lifting” in barochamber to simulated altitude of 5600 m a.s.l. for 1 h/day on 3 consecutive days before surgical manipulation. Expressions of SIRT1, SIRT3 in brain tissue, and histopathological changes of the hippocampi were examined. It was shown that 8-week chronic hypoperfusion of the brain, caused by unilateral occlusion of the common carotid artery, was accompanied by injury to the neurons of the hippocampi of both hemispheres, which was more pronounced on the side of the occlusion. This damage, as well as the mechanisms of neuroprotection induced by hypoxic preconditioning, were maintained for at least 8 weeks by mechanisms mediated through a7nAChRs. Deficite of a7nAChRs was accompanied with reduction of neuronal damage caused CCH in 8 weeks, as well as preconditioning effects, and lead to compensatory activation of regulatory and protective mechanisms mediated by SIRT1, in normal conditions and in CCH. In wild-type (C57) mice, protective mechanisms in CCH were realized to a greater extent by increased expression of SIRT3 in both hemispheres of the brain.

RESUMEN: Se sabe que el precondicionamiento hipóxico induce neuroprotección, pero aún se desconocen sus efectos y vías en la patología cerebral crónica. El objetivo fue establecer la participación de la subunidad a7 de los receptores nicotínicos de acetilcolina (a7nAchR) y las sirtuinas de tipo 1 (SIRT1) y 3 (SIRT3) en los efectos del precondicionamiento hipóxico hipobárico sobre el daño cerebral en ratones con hipoperfusión cerebral crónica causada por la oclusión de la arteria carótida común izquierda. Los ratones macho C57/6j (C57, tipo salvaje) y a7nAchRs(-/-) se dividieron en seis grupos experimentales (10 ratones por grupo): C57 con operación simulada, C57 con hipoperfusión cerebral crónica, C57 con precondicionamiento hipobárico hipóxico y crónica. hipoperfusión cerebral, ratones a7nAchRs(-/-) operados de forma simulada, a7nAchRs(-/-) con hipoperfusión cerebral crónica, a7nAchRs(-/-) con precondicionamiento hipobárico hipóxico e hipoperfusión cerebral crónica. Para el preacondicionamiento, los ratones fueron expuestos a hipoxia "levantándolos" en una cámara de barro a una altitud simulada de 5600 m s.n.m. durante 1 h/día durante 3 días consecutivos antes de la manipulación quirúrgica. Se examinaron las expresiones de SIRT1, SIRT3 en tejido cerebral y los cambios histopatológicos de los hipocampos. Se demostró que la hipoperfusión cerebral crónica de 8 semanas, causada por la oclusión unilateral de la arteria carótida común, se acompañaba de lesión de las neuronas del hipocampo de ambos hemisferios y que era más pronunciada en el lado de la oclusión. Este daño, así como los mecanismos de neuroprotección inducidos por el precondicionamiento hipóxico, se mantuvieron durante al menos 8 semanas mediante mecanismos mediados por a7nAChR. El déficit de a7nAChR se acompañó de una reducción del daño neuronal causado por CCH en 8 semanas, así como de efectos de precondicionamiento, y condujo a una activación compensatoria de mecanismos reguladores y protectores mediados por SIRT1, en condiciones normales y en CCH. En ratones de tipo salvaje (C57), los mecanismos de protección en CCH se realizaron en mayor medida mediante una mayor expresión de SIRT3 en ambos hemisfe- rios del cerebro.

Abstract Objective This study was designed to investigate the effect of butorphanol-soaked nasal packing on analgesia and sleep quality in patients undergoing bilateral endoscopic nasal surgery. Methods Sixty-six patients were enrolled and randomly allocated into three groups: group B1 (butorphanol 0.03 mg/kg), group B2 (butorphanol 0.04 mg/kg) and group N (control group). The primary outcome was postoperative pain scores evaluated by a Visual Analogue Scale (VAS) at 2 h (T1), 8 h (T2), 24 h (T3) and 48 h (T4) after surgery. Secondary outcome was postoperative sleep quality measured using Subjective Sleep Quality Value (SSQV). Results Postoperative VAS scores of butorphanol groups were significantly lower than the control group at T2, T3 and T4. VAS scores at each time point did not differ between groups B1 and B2. On the first and second nights after surgery, SSQV was higher in butorphanol groups than in the control group. There were no significant differences in SSQV1 and SSQV2 between group B1 and group B2. The incidence of respiratory depression, dizziness, agitation and rescue analgesic use did not show difference among three groups. Conclusions Butorphanol-soaked nasal packing can reduce pain and improve sleep quality after bilateral endoscopic nasal surgery without increasing adverse effects. A concentration of 0.03 mg/kg may be appropriate for clinical application. Level of Evidence Level 1B. butorphanolsoaked soaked Sixtysix Sixty six B 003 0 03 0.0 mg/kg, mgkg , mg kg 004 04 . group) (VAS T1, T1 T (T1) T2 (T2) (T3 4 T4 (T4 SSQV. (SSQV) depression dizziness Butorphanolsoaked Butorphanol effects application 1B 00 0. (T1 (T2 (T (SSQV

Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats. dysfunction However situations study rats 14 (7 7 females birth nd th PSD PSD9 caspase3 caspase 3 caspase- dosedependent dose dependent manner 2h h 2 compensated addition extended attenuated conclusion durationdependent duration Baxcaspase3dependent Baxcaspasedependent 1 ( Baxcaspase

Resumo O uso de fertilizantes afeta não apenas a fertilidade do solo e o rendimento das culturas, mas também altera significativamente a estrutura taxonômica da microbiocenose do solo. Aqui, com base em experimento de campo estacionário, estudou-se a influência do fertilizante organomineral (FOM), modificado pela bactéria Bacillus subtilis (H-13), em comparação com diferentes sistemas de fertilizantes (orgânico, mineral, organomineral) em (i) rendimento da colheita, (ii) propriedades físicas e químicas, e (iii) diversidade alfa e beta da comunidade microbiana Albic Retisol (Loamic, Aric, Cutanic, Differentic, Ochric). O experimento foi conduzido sob duas condições: com calagem (pHKCl - 5,9) e sem calagem (pHKCl - 5,1). O uso apenas de esterco bovino foi menos eficaz do que sua coaplicação com fertilizantes minerais em metade das doses. Um efeito semelhante foi obtido ao aplicar FOM. Além disso, o uso de FOM contribui para um aumento significativo nas reservas de carbono orgânico do solo na camada de solo de 0-20 cm em 18%-32%. O sequenciamento de alto rendimento das bibliotecas de sequências do gene variável V4 do rRNA 16S identificou 10.759 táxons pertencentes a 456 gêneros, classificados em 34 filos (31 bacterianos e 3 arqueanos). A aplicação unilateral de fertilizantes minerais levou a uma diminuição significativa da diversidade alfa da estrutura das comunidades microbianas do solo (OTE [outras coisas iguais] e índice de Shannon). Foi observada uma aglutinação da microbiota nas variantes com e sem a aplicação de esterco bovino. O estudo revelou que a estrutura taxonômica da microbiocenose é formada sob a influência de dois fatores principais: cultura de rotação de culturas e fertilizantes aplicados. O tipo de cultura cultivada determina a dinâmica do microbiota ao nível de taxa maiores, como os domínios, e os fertilizantes afetam a estrutura da comunidade microbiana a um nível taxonômico inferior (filos, ordens, famílias). Com base na análise Deseq, foram identificados taxa marcadores, de acordo com a participação dos quais é possível determinar o tipo de cultura cultivada e os fertilizantes utilizados na experiência. A compreensão da dinâmica da associação de taxa e de outros fatores influentes pode levar à criação de sistemas universais de indicaçadores metagenômicos, onde o rastreio da dinâmica das comunidades microbianas permitirá uma avaliação abrangente do estado agroecológico dos solos e decisões oportunas para prevenir a sua degradação. Aqui estacionário estudouse estudou se FOM, , (FOM) H13, H13 H 13 (H-13) orgânico, (orgânico mineral i (i colheita ii (ii químicas iii (iii Loamic, Loamic (Loamic Aric Cutanic Differentic Ochric. Ochric . Ochric) condições pHKCl 5,9 59 5 9 5,1. 51 5,1 1 5,1) doses disso 020 0 20 0-2 18%32%. 1832 18% 32%. 18 32 18%-32% V S 10759 10 759 10.75 45 gêneros 31 (3 arqueanos. arqueanos arqueanos) OTE outras iguais Shannon. Shannon Shannon) principais aplicados maiores domínios filos, (filos ordens famílias. famílias famílias) Deseq marcadores experiência metagenômicos degradação (FOM H1 (H-13 5, 02 2 0- 18%32% 183 32% 18%-32 1075 75 10.7 4 ( (H-1 18%32 18%-3 107 7 10. (H- 18%3 18%- (H

Abstract The use of fertilizers affects not only the soil fertility and crop yield, but also significantly changes the taxonomic structure of the soil microbiocenosis. Here, based on stationary field experiment, we studied the influence of organo-mineral fertilizer (ОМF), modified by bacteria Bacillus subtilis, H-13 in comparison with different fertilizer systems (organic, mineral, organo-mineral) on (i) crop yield, (ii) physical and chemical properties, and (iii) alpha and beta diversity of the microbial community Albic Retisol (Loamic, Aric, Cutanic, Differentic, Ochric). The studies were carried out against the background of liming (рНКCl – 5.9) and without it (рНКCl – 5.1). The use of only one cattle farmyard manure was less effective than its co-application with mineral fertilizers in half doses. A similar effect was obtained when applying ОМF. In addition, the use of OMF contributes to a significant increase in the reserves of soil organic carbon in the soil layer 0-20 cm by 18%-32%. Using high-throughput sequencing of the 16S rRNA variable V4 gene sequence libraries, 10.759 taxa from 456 genera were identified, assigned to 34 fila (31 bacterial and 3 archaeotic. Unilateral application of mineral fertilizers leads to a significant decrease in the alpha diversity of the structure of soil microbial communities (OTE (other things equal) and Shannon index). A clear clustering of the microbiota was found in the variants with and without the introduction of сattle farmyard manure. It is revealed that the taxonomic structure of the microbiocenosis is formed under the influence of two main factors: crop rotation culture and applied fertilizers. The type of cultivated crop determines the dynamics of the microbiota at the level of larger taxa, such as domains, and fertilizers affect the structure of the microbial community at alower taxonomic level (phyla, orders, bloodlines). On the basis of the Deseq analysis, marker taxa were identified, according to the share participation of which it is possible to determine the type of cultivated crop and fertilizers used in the experiment. Understanding the dynamics of taxa association and other influential factors can lead to the creation of universal systems of metagenomic indication, where tracking the dynamics of microbial communities will allow for a comprehensive assessment of the agroecological state of soils and timely decisions to prevent their degradation. yield Here experiment organomineral organo ОМF, ОМF , (ОМF) subtilis H13 H 13 H-1 organic, (organic i (i ii (ii properties iii (iii Loamic, Loamic (Loamic Aric Cutanic Differentic Ochric. Ochric . Ochric) рНКCl 5.9 59 5 9 5.1. 51 5.1 1 5.1) coapplication co doses addition 020 0 20 0-2 18%32%. 1832 18% 32%. 18 32 18%-32% highthroughput high throughput S V libraries 10759 10 759 10.75 45 identified 31 (3 archaeotic OTE equal index. index index) domains phyla, phyla (phyla orders bloodlines. bloodlines bloodlines) analysis indication degradation (ОМF H1 H- 5. 02 2 0- 18%32% 183 32% 18%-32 1075 75 10.7 4 ( 18%32 18%-3 107 7 10. 18%3 18%-

Abstract Objective To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. Methods AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). Results During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. Conclusion Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality. Dickkopf3 Dickkopf 3 Dickkopf- sDKK (sDKK3 (END inhospital hospital (AIS n 200 Scale Dkk ELISA 72h h Xtile X tile allcause all cause death hospitalization DKK admission. . admission) 130 13 0 13. 1154 11 54 11.5 3/26. 326 3/26 26 (3/26) 93.0 930 93 (93. pg/mL, pgmL pg/mL , pg mL 435 43 5 43. 20/48. 2048 20/48 20 48 (20/48) 1.188fold 1188fold fold 1.188 1 188 OR 1188 9 10551369 055 369 1.055‒1.369 0.0001. 00001 0.0001 0001 0.0001) However (sDKK 115 11. 32 3/2 2 (3/26 93. (93 204 20/4 (20/48 188fold 1.18 18 118 1055136 05 36 1.055‒1.36 0000 0.000 000 3/ (3/2 (9 20/ (20/4 1.1 105513 1.055‒1.3 0.00 00 (3/ ( (20/ 1. 10551 1.055‒1. 0.0 (3 (20 1055 1.055‒1 0. (2 105 1.055‒ 10 1.055 1.05 1.0

Abstract Histone deacetylase 9 (HDAC9) is a histone deacetylase (HDAC) subtype IIa protein that deacetylates histone 3 (H3), histone 4 (H4), and nonhistone proteins in vivo to alter chromosomal shape and regulate gene transcription. There have been few studies on the regulatory influence of the HDAC9 gene on the differentiation of chicken embryonic stem cells (cESCs) into male germ cells, and the significance of HDAC9 is still unknown. Therefore, we explored the specific role of HDAC9 during differentiation of the cESCs of Jilin Luhua chickens through inhibition or overexpression. In medium supplemented with 10-5 mol/L retinoic acid (RA), cESCs were stimulated to develop into germ cells. HDAC9 and germline marker gene mRNA and protein levels were measured using qRT‒PCR and western blotting. During the differentiation of cESCs into male germ cells, overexpression of the HDAC9 gene greatly increased the mRNA and protein expression levels of the germline marker genes Stra8, Dazl, c-kit, and integrin ɑ6. The HDAC9 inhibitor TMP195 significantly decreased the mRNA and protein expression levels of the above markers. In summary, HDAC9 positively regulates the differentiation of cESCs. HDAC (HDAC9 (HDAC H3, H3 H , (H3) H4, H4 (H4) transcription (cESCs unknown Therefore 105 10 5 10- molL mol L RA, RA (RA) qRTPCR qRT PCR blotting Stra8 Stra Dazl ckit, ckit c kit, kit c-kit ɑ6 ɑ TMP TMP19 markers summary (H3 (H4 1 (RA TMP1 (H

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets. nonsmall non small NSCLC, , (NSCLC) exploration pharmacology bioinformatics validation research HIT20 HIT HIT2 0 HIT2.0 STD CTD DisGeNET proteinprotein protein PPI, (PPI) GO, (GO) KEGG, (KEGG) docking A54 cells NCIH460, NCIH460 NCIH NCI H460, H460 H NCI-H460 realtime real time PCR 6 databases cancerrelated related PI3KAKT PIKAKT PI3K AKT PI K pathway microRNAs HIF1 HIF 1 HIF- etc CASP3 CASP CTNNB1 CTNNB JUN IL6 IL MAPK3 HIF1A HIFA STAT3 STAT AKT1 TP53 TP CCND1 CCND VEGFA EGFR downregulated down regulated 6, IL-6 (NSCLC HIT2. (PPI (GO (KEGG A5 NCIH46 H46 NCI-H46 KAKT PIK TP5 IL- NCIH4 H4 NCI-H4 NCI-H

Resumo Fundamento A hipertrofia cardíaca patológica (HC) sustentada é um fator de risco independente para aumento da incidência e mortalidade de eventos cardiovasculares. Objetivos Esta pesquisa foi projetada para desvendar o papel do RNA não codificante longo (LncRNA) CCAT2 na progressão da HC. Métodos Procedimentos de constrição aórtica transversal (TAC) foram conduzidos para construir um modelo de HC in vivo induzido por sobrecarga de pressão. O tratamento com angiotensina II (Ang II) foi utilizado para induzir células hipertróficas de cardiomiócitos de rato H9c2. Resultados Os resultados in vivo mostraram que o silenciamento de CCAT2 reduziu a área de superfície dos cardiomiócitos, aliviou a fibrose cardíaca e diminuiu os níveis de β-MHC, ANP e BNP em modelos de camundongos HC. Os resultados in vitro revelaram que o knockdown de CCAT2 reduziu a área de superfície celular e atenuou os níveis de β-MHC, ANP e BNP em células hipertróficas H9c2. Além disso, o silenciamento de CCAT2 diminuiu os níveis de β-catenina ativa, GSK-3β fosforilada e genes alvo Wnt (c-Myc, ciclinaD1 e c-Jun) em camundongos HC e células H9c2 hipertróficas. É importante ressaltar que o tratamento com o ativador da via Wnt / β-catenina LiCl reverteu a supressão do knockdown de CCAT2 na área de superfície celular H9c2 e nos níveis de MHC, ANP e BNP. Conclusões Coletivamente, o silenciamento do CCAT2 desempenha um papel protetor contra a HC através da inativação da sinalização Wnt/β-catenina, o que sugere que o CCAT2 pode se tornar um alvo terapêutico promissor para o HC. (HC cardiovasculares LncRNA (LncRNA CCAT TAC (TAC pressão Ang Hc H c βMHC, βMHC β MHC β-MHC disso βcatenina catenina ativa GSK3β GSKβ GSK 3β cMyc, cMyc Myc, Myc (c-Myc ciclinaD cJun Jun c-Jun H9c Coletivamente Wnt/βcatenina, Wntβcatenina Wnt/β catenina, Wnt/β-catenina Wnt/βcatenina Wntβ

Abstract Background Sustained pathological cardiac hypertrophy (CH) is an independent risk factor for increased incidence and mortality of cardiovascular events. Objectives This research was designed to unravel the role of long non-coding RNA (LncRNA) CCAT2 in CH progression. Methods Transverse aortic constriction (TAC) procedures were conducted to construct a pressure overload-induced in vivo CH model. Angiotensin II (Ang II) treatment was utilized to induce hypertrophic rat cardiomyocyte H9c2 cells. Results In vivo results showed that silencing of CCAT2 reduced cardiomyocyte surface area, alleviated cardiac fibrosis, and decreased β-MHC, ANP, and BNP levels in CH mouse models. In vitro results revealed that CCAT2 knockdown reduced cell surface area and attenuated β-MHC, ANP, and BNP levels in hypertrophic H9c2 cells. Besides, CCAT2 silencing decreased the levels of active β-catenin, phosphorylated-GSK-3β, and Wnt target genes (c-Myc, cyclinD1, and c-Jun) in CH mice and hypertrophic H9c2 cells. Importantly, treatment with the Wnt/β-catenin pathway activator LiCl reversed the suppression of CCAT2 knockdown on H9c2 cell surface area and MHC, ANP, and BNP levels. Conclusions Collectively, CCAT2 silencing plays a protective role against CH through inactivating the Wnt/β-catenin signaling, which suggests that CCAT2 might become a promising therapeutic target for CH. (CH events noncoding non coding LncRNA (LncRNA CCAT progression TAC (TAC overloadinduced overload induced model Ang Hc H c H9c cells fibrosis βMHC, βMHC β MHC β-MHC ANP models Besides βcatenin, βcatenin catenin, catenin β-catenin phosphorylatedGSK3β, phosphorylatedGSK3β phosphorylatedGSKβ phosphorylated GSK 3β, 3β phosphorylated-GSK-3β cMyc, cMyc Myc, Myc (c-Myc cyclinD1 cyclinD cJun Jun c-Jun Importantly Wnt/βcatenin Wntβcatenin Wnt/β Collectively signaling phosphorylatedGSK Wntβ

ABSTRACT Objective: To clarify the association between smoking and stricture recurrence after urethroplasty. Materials and Methods: Pubmed, Web of Science, Embase, and Cochrane databases were searched with keywords: “urethroplasty,” “buccal mucosa graft urethroplasty,” “oral mucosa graft urethroplasty,” “excision and primary anastomosis urethroplasty,” “urethral stricture recurrence” until July 1, 2022. Inclusion and exclusion criteria were based on PICOS principles. The quality of included studies was assessed by Newcastle-Ottawa Scale (N.O.S.) system. Hazard ratio (H.R.), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test the stability of the meta-analysis. I2 was calculated to evaluate heterogeneity. Publication biases were assessed by Egger's and Begg's tests. Funnel plots of univariate analysis and multivariate analysis were also offered. Results: Twenty one studies with 6791 patients were involved in this meta-analysis. The analysis results of the two stages were consistent. In the univariate meta-analysis stage, 18 studies with 5811 patients were pooled, and the result indicated that smoking might promote stricture recurrence (RR=1.32, P=0.001). Based on the adjusted estimate, 11 studies with 3176 patients were pooled in the multivariate meta-analysis stage, and the result indicated that smoking might promote stricture recurrence (RR=1.35, P=0.049). There was no significant heterogeneity in both the univariate and multivariate stages. Conclusion: Our study demonstrates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery. Objective Methods Pubmed Science Embase keywords urethroplasty, “urethroplasty, buccal oral excision urethral 1 2022 principles NewcastleOttawa Newcastle Ottawa N.O.S. NOS N O S (N.O.S. system H.R., HR H.R. , H R (H.R.) OR, OR (OR) RR (RR 95 CI (CI recalculated re Metaanalysis Meta 150 15 0 15. separately metaanalysis. metaanalysis meta analysis. I Eggers Egger s Beggs Begg tests offered Results 679 consistent stage 581 RR=1.32, RR132 32 (RR=1.32 P=0.001. P0001 P P=0.001 . 001 P=0.001) estimate 317 RR=1.35, RR135 35 (RR=1.35 P=0.049. P0049 P=0.049 049 P=0.049) Conclusion surgery “urethroplasty 202 N.O.S (N.O.S H.R (H.R. (OR 9 67 58 RR=1.32 RR13 3 (RR=1.3 P000 P=0.00 00 31 RR=1.35 P004 P=0.04 04 20 (H.R 6 5 RR=1.3 RR1 (RR=1. P00 P=0.0 2 RR=1. (RR=1 P0 P=0. RR=1 (RR= P=0 RR= P=

ABSTRACT Purpose: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. Methods: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Results: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. Conclusions: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future. Purpose (ESCC diagnosis miR29c3p miRcp miR 29c 3p c p types Yet previously Methods SERPINH (SERPINH1 analysis Thereafter HSP47 HSP (HSP47 realtime real time reaction viability proliferation migration invasion CCK8 CCK formation transwell assays respectively factorA factor A VEGFA, , (VEGFA) Wnt1, Wnt1 1, Wnt-1 catenin, catenin ?-catenin pcatenin blot enzymelinked enzyme linked assay BML284 BML 284 BML-28 Results Herein progression Meanwhile miR29c3p. 3p. activation Conclusions future (SERPINH HSP4 (HSP4 (VEGFA Wnt- BML28 28 BML-2 (HSP BML2 2 BML-

Abstract Polysaccharides are a class of biological macromolecules made up of sugar chains with multiple glycosidic bonds. To explore the extracted, purified, carboxymethylated and phosphorylated modified to obtained carboxymethylated polysaccharides (HSPS) and phosphorylated polysaccharides (HSPP), and the HSPS and HSPP were characterized and analyzed, and their antioxidant activity measured. Response surface design was used for the synthesis process of HSPS and HSPP, the structure characterization and antioxidant activities of HSPS and HSPP were evaluated. The results showed that the Mw and Mn of HSP were 14.66 kDa and 8.39 kDa, respectively. The monosaccharides were mainly galactose, glucose, xylose, and arabinose in a molar ratio of 37.68%: 24.43%: 13.63%: 9.18%. The optimal synthesis conditions for HSPS were as follows: reaction time of 2.01 h, reaction temperature of 44.61°C and the amount of monochloroacetic acid necessary was 1.18 g. The optimal synthesis conditions for HSPP were: reaction time of 4.28 h, reaction temperature of 80.78°C, and reaction pH of 8.98. HSPS and HSPP have scavenging effects on ABTS, super oxideanion and hydroxyl radicals. The HSPS and HSPP were characterized and analyzed, and their antioxidant activity measured. bonds extracted purified (HSPS , (HSPP) analyzed measured evaluated 1466 14 66 14.6 839 8 39 8.3 respectively galactose glucose xylose 37.68% 3768 37 68 24.43% 2443 24 43 13.63% 1363 13 63 918 9 18 9.18% follows 201 2 01 2.0 h 4461C C 44 61 118 1 1.1 g 428 4 28 4.2 8078C 80 78 80.78°C 898 98 8.98 ABTS radicals (HSPP 146 6 14. 83 3 8. 37.68 376 24.43 244 13.63 136 91 9.18 20 0 2. 11 1. 42 4. 7 89 8.9 37.6 24.4 13.6 9.1 37. 24. 13. 9.

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People’s Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. Objective miRNA122 miRNA 122 miRNA-12 diagnosis severity (ACI Method 6 Peoples People s 1 2019 selected collected age sex history CReactive C Reactive CRP , [CRP] Interleukin6 Interleukin Interleukin- IL6, IL6 IL [IL-6] PCT, PCT [PCT] GelatinaseAssociated Gelatinase Associated NGAL. . [NGAL]) (NIHSS shortterm short term [mRS] recorded reversetranscription reverse transcription RealTime Real Time RTQPCR, RTQPCR RT QPCR (RT-QPCR) analyzed people (HUVECs apoptosisrelated related Bcl2, Bcl2 Bcl 2, 2 Caspase3, Caspase3 Caspase 3, angiogenesisrelated angiogenesis Hes1 Hes Notch1 Notch VEGF (VEGF) CCNG blot miRNA122, 122, dualluciferase Result 0929 0 929 0.929 95 08750983 875 983 0.875‒0.983 cutoff cut off 1397 397 1.397 6, IL-6 0.05 005 05 CPR h 72h proapoptotic pro apoptotic caspase3 caspase caspase- antiapoptotic anti Bcl- Caspase- 3UTR UTR miRNA122. 122. miRNA12 12 miRNA-1 201 [CRP [IL-6 [PCT [NGAL] [mRS (RT-QPCR (VEGF 092 92 0.92 9 0875098 87 98 0.875‒0.98 139 39 1.39 IL- 0.0 00 miRNA1 miRNA- 20 [IL- [NGAL 09 0.9 087509 8 0.875‒0.9 13 1.3 0. [IL 08750 0.875‒0. 1. 0875 0.875‒0 087 0.875‒ 08 0.875 0.87 0.8

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole. coadministrated 13 1 3 1/ practice CYPC CYP C CYP2C1 drugdrug drug interactionsDDIs interactions interactions(DDIs (PBPK error AUC024, AUC024 AUC AUC0 24, 24 AUC0-24 tmax population 146h h PMs, PMs , (PMs) IMs (IMs metabolizersEMs, metabolizersEMs EMs metabolizers(EMs) respectively CYP2C AUC02 2 AUC0-2 (PMs metabolizers(EMs AUC0-

ABSTRACT Purpose: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2S, TNF-α and mitoKATP in melatonin-mediated effects in RIPC. Methods: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. Results: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). Conclusions: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels. Purpose (RIPC (IR However RIPCinduced induced explored HS H S TNFα TNF α melatoninmediated mediated Methods cuff 2 ramelteoninduced apparatus Results LDH1, LDH1 LDH 1, 1 LDH-1 LVDP. LVDP . (LVDP) plasma, , plasma) heart luzindole, luzindole (luzindole) hexamethonium (hexamethonium 5hydroxydecanoic hydroxydecanoic acid. acid acid) Conclusions channels Ramelteoninduced Ramelteon LDH- (LVDP (luzindole