Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways. castrationresistant castration resistant (CRPC methods MMP12 MMP 12 (MMP)-1 ECM (ECM components However MMP-1 understood action coculture co culture MMP12. 12. CD36CPT1 CDCPT CD36 CPT1 CD CPT CD36/CPT P62LC3 PLC P62 LC3 P LC P62/LC pathways respectively Moreover MMP12knockdown MMPknockdown knockdown growth results MMP1 1 (MMP)- MMP- CD36CPT CD3 P62LC P6 (MMP) (MMP

Resumo Objetivo Avaliar os efeitos do modelo de enfermagem de Newman na qualidade de vida e recuperação muscular do assoalho pélvico em pacientes com disfunção do assoalho pélvico pós-parto. Métodos Oitenta e oito pacientes com disfunção do assoalho pélvico pós-parto tratadas de janeiro a abril de 2023 foram divididas em grupo Observação e Controle (n=44) por meio de tabela de números aleatórios. O grupo Controle recebeu enfermagem de rotina e o grupo Observação recebeu cuidados de enfermagem de Newman. A qualidade de vida foi avaliada pelo Short Form-36 Health Status Questionnaire. A função do assoalho pélvico foi avaliada por meio do Pelvic Floor Impact Questionnaire-7 (PFIQ7) e da Pelvic Organ Prolapse Quantification (POPQ). Resultados Após a intervenção, as pontuações de aspectos físico, emocional, capacidade funcional, social e motor do grupo Observação foram superiores às do grupo Controle (P<0,05). As pontuações da Escala de Autoavaliação de Ansiedade e da Escala de Autoavaliação de Depressão do grupo Observação foram inferiores às do grupo Controle. O nível de conhecimento sobre a doença foi maior no grupo Observação do que no grupo Controle (P<0,05). O grupo Observação apresentou maior força das fibras musculares tipo I e II, e menores graus de fadiga das fibras musculares tipo I e II do que o grupo Controle (P<0,05). As pontuações PEIQ7 e POPQ do grupo Observação foram inferiores às do grupo Controle (P<0,05). Conclusão O modelo de enfermagem de Newman ajuda a melhorar a função do assoalho pélvico, a qualidade de vida e o conhecimento sobre a doença, além de aliviar a ansiedade, a depressão e outras emoções adversas. pósparto. pósparto pós parto. parto 202 n=44 n44 n 44 (n=44 aleatórios Form36 Form 36 Form-3 Questionnaire Questionnaire7 7 Questionnaire- PFIQ7 PFIQ (PFIQ7 POPQ. . (POPQ) intervenção físico emocional funcional P<0,05. P005 P P<0,05 0 05 (P<0,05) PEIQ ansiedade adversas 20 n=4 n4 4 (n=4 Form3 3 Form- (PFIQ (POPQ P00 P<0,0 (P<0,05 2 n= (n= P0 P<0, (P<0,0 (n P<0 (P<0, P< (P<0 (P< (P

Abstract Objective We aimed to evaluate the effects of the Newman nursing model on the quality of life and pelvic floor muscle recovery in patients with postpartum pelvic floor dysfunction. Methods Eighty-eight patients with postpartum pelvic floor dysfunction treated from January to April 2023 were divided into observation and control groups (n=44) using a random number table. The control group was given routine nursing, based on which the observation group was given Newman nursing. The quality of life was assessed by the Short Form-36 Health Status Questionnaire. The pelvic floor function was evaluated using the Pelvic Floor Impact Questionnaire-7 (PEIQ7) and Pelvic Organ Prolapse Quantification (POPQ). Results After intervention, the scores of role physical, language communication, physical functioning, social functioning and motor functioning of the observation group were higher than those of the control group (P<0.05). The Self-rating Anxiety Scale and Self-rating Depression Scale scores of the observation group were lower than those of the control group. The awareness rate of disease knowledge of the observation group was higher than that of the control group (P<0.05). The observation group had higher class I and class II muscle fiber potentials, whereas lower class I and class II muscle fiber fatigue degrees than those of the control group (P<0.05). The PEIQ7 and POPQ scores of the observation group were lower than those of the control group (P<0.05). Conclusion Newman nursing helps improve the pelvic floor function, quality of life and awareness of the disease knowledge, and relieve anxiety, depression and other adverse emotions. Eightyeight Eighty eight 202 n=44 n44 n 44 (n=44 table Form36 Form 36 Form-3 Questionnaire Questionnaire7 7 Questionnaire- PEIQ (PEIQ7 POPQ. . (POPQ) intervention communication P<0.05. P005 P P<0.05 0 05 (P<0.05) Selfrating Self rating potentials anxiety emotions 20 n=4 n4 4 (n=4 Form3 3 Form- (PEIQ (POPQ P00 P<0.0 (P<0.05 2 n= (n= P0 P<0. (P<0.0 (n P<0 (P<0. P< (P<0 (P< (P

Resumen Objetivo Evaluar los efectos del modelo de enfermería de Newman en la calidad de vida y recuperación muscular del suelo pélvico en pacientes con disfunción del suelo pélvico posparto. Métodos Un grupo de 88 pacientes con disfunción del suelo pélvico posparto, tratadas de enero a abril de 2023, fue dividido en dos grupos, uno de observación y otro de control (n=44) mediante una tabla de número aleatorios. El grupo de control recibió cuidados de enfermería de rutina y el grupo de observación recibió cuidados de enfermería de Newman. Se utilizó el Short Form-36 Health Status Questionnaire para evaluar la calidad de vida. La función del suelo pélvico se evaluó mediante el Pelvic Floor Impact Questionnaire-7 (PFIQ7) y la Pelvic Organ Prolapse Quantification (POPQ). Resultados Después de la intervención, el puntaje de los aspectos físico, emocional, social, motor y de la capacidad funcional del grupo de observación fue más alto que el del grupo de control (P<0,05). El puntaje de la Escala de Autoevaluación de Ansiedad y de la Escala de Autoevaluación de Depresión del grupo de observación fue más bajo que el del grupo de control. El nivel de conocimiento sobre la enfermedad fue mayor en el grupo de observación que en el grupo de control (P<0,05). El grupo de observación presentó mayor fuerza de las fibras musculares tipo I y II y un nivel menor de fatiga de las fibras musculares tipo I y II que el grupo de control (P<0,05). El puntaje de PEIQ7 y POPQ del grupo de observación fue más bajo que el del grupo de control (P<0,05). Conclusión El modelo de enfermería de Newman ayuda a mejorar la función del suelo pélvico, la calidad de vida y el conocimiento sobre la enfermedad, además de calmar la ansiedad, la depresión y otras emociones adversas. posparto 8 2023 grupos n=44 n44 n 44 (n=44 aleatorios Form36 Form 36 Form-3 Questionnaire7 7 Questionnaire- PFIQ7 PFIQ (PFIQ7 POPQ. . (POPQ) intervención físico emocional social P<0,05. P005 P P<0,05 0 05 (P<0,05) PEIQ ansiedad adversas 202 n=4 n4 4 (n=4 Form3 3 Form- (PFIQ (POPQ P00 P<0,0 (P<0,05 20 n= (n= P0 P<0, (P<0,0 2 (n P<0 (P<0, P< (P<0 (P< (P

Abstract Background With the fast-paced advancements of robot technology, human–robot interaction (HRI) has become increasingly popular and complex, and self-efficacy in HRI has received extensive attention. Despite its popularity, this topic remains understudied in China. Objective In order to provide a psychometrically sound instrument in China, this study aimed to translate and validate the Self-Efficacy in Human–Robot Interaction Scale (SE-HRI) in two Chinese adult samples (N1 = 300, N2 = 500). Methods The data was analyzed by SPSS 26.0 and Amos 24.0. Item analysis and exploratory factor analysis were conducted using Sample 1 data. Confirmatory factor analysis, criterion-related validity analysis, and reliability analysis were then performed using Sample 2 data. Results The results revealed that the Chinese SE-HRI scale consisted of 13 items in a two-factor model, suggesting a good model fit. Moreover, general self-efficacy and willingness to accept the use of artificial intelligence (AI) were both positively correlated with self-efficacy in HRI, while negative attitudes toward robots showed an inverse correlation, proving the Chinese SE-HRI scale exhibited excellent criterion-related validity. Conclusion The Chinese SE-HRI scale is a reliable assessment tool for evaluating self-efficacy in HRI in China. The study discussed implications and limitations, and suggested future directions. fastpaced fast paced technology humanrobot human (HRI complex selfefficacy self efficacy attention popularity China SelfEfficacy Self Efficacy HumanRobot Human Robot SEHRI SE (SE-HRI N1 N (N 300 500. 500 . 500) 260 26 0 26. 240 24 24.0 criterionrelated criterion related twofactor fit Moreover AI (AI correlation limitations directions 30 50 24. 3 5

ABSTRACT In order to enhance the quality and mechanical properties of 3D printing carbon fiber reinforced composite (CFRP) workpiece, this paper prepares 3D printing CFRP laminates by proposing a layered coherent composite scanning path, and carries out orthogonal tests and single factor tests to disclose the effects of different process parameters (i.e., layer thickness, first layer thickness, nozzle temperature and printing speed) on the mechanical performance of the CFRP workpieces. Moreover, The grey relation analysis method is used to analyze the multi-objective parameters of the orthogonal tests results and the process parameters of 3D printing CFRP are optimized based on the tests results. The research results show that the process parameters of 3D printed CFRP can be ranked as delamination thickness, nozzle temperature, first layer thickness and printing speed, in descending order of the impact on the mechanical property of the CFRP laminates. the optimal process parameters for 3D printing include a layer thickness of 0.25 mm, a first layer thickness e of 0.2 mm, a nozzle temperature of 180°C, and printing speed of 45 mm/s. Under this parameter combination, the tensile strength, bending strength, and the interlaminar shear strength (ILSS) of the samples are 52.77 MPa, 276.63 MPa and 38.56 Mpa respectively, and the grey correlation degree increased to 0.845. D (CFRP workpiece path i.e., ie i (i.e. workpieces Moreover multiobjective multi objective 025 0 25 mm 02 2 0. 180C C 180 180°C 4 mms s mm/s combination ILSS (ILSS 5277 52 77 52.7 27663 276 63 276.6 3856 38 56 38.5 respectively 0845 845 0.845 i.e. (i.e 18 527 5 7 52. 2766 27 6 276. 385 3 38. 084 84 0.84 i.e 1 08 8 0.8

Abstract Objectives To determine whether tinnitus negatively impacts the accuracy of sound source localization in participants with normal hearing. Methods Seventy-five participants with tinnitus and 74 without tinnitus were enrolled in this study. The accuracy of sound source discrimination on the horizontal plane was compared between the two participant groups. The test equipment consisted of 37 loudspeakers arranged in a 180° arc facing forward with 5° intervals between them. The stimuli were pure tones of 0.25, 0.5, 1, 2, 4, and 8 kHz at 50 dB SPL. The stimuli were divided into three groups: low frequency (LF: 0.25, 0.5, and 1 kHz), 2 kHz, and high frequency (HF: 4 and 8 kHz) stimuli. Results The Root Mean Square Error (RMSE) score of all the stimuli in the tinnitus group was significantly higher than that in the control group (13.45 ± 3.34 vs. 11.44 ± 2.56, p = 4.115, t < 0.001). The RMSE scores at LF, 2 kHz, and HF were significantly higher in the tinnitus group than those in the control group (LF: 11.66 ± 3.62 vs. 10.04 ± 3.13, t = 2.918, p = 0.004; 2 kHz: 16.63 ± 5.45 vs. 14.43 ± 4.52, t = 2.690, p = 0.008; HF: 13.42 ± 4.74 vs. 11.14 ± 3.68, t = 3.292, p = 0.001). Thus, the accuracy of sound source discrimination in participants with tinnitus was significantly worse than that in those without tinnitus, despite the stimuli frequency. There was no difference in the ability to localize the sound of the matched frequency and other frequencies (12.86 ± 6.29 vs. 13.87 ± 3.14, t = 1.204, p = 0.236). Additionally, there was no correlation observed between the loudness of tinnitus and RMSE scores (r = 0.096, p = 0.434), and the Tinnitus Handicap Inventory (THI) and RMSE scores (r = −0.056, p = 0.648). Conclusions Our present data suggest that tinnitus negatively impacted sound source localization accuracy, even when participants had normal hearing. The matched pitch and loudness and the impact of tinnitus on patients’ daily lives were not related to the sound source localization ability. Level of evidence 4. hearing Seventyfive Seventy five 7 study groups 3 180 5 them 025 0 25 0.25 05 0.5 SPL LF (LF , (HF (RMSE 13.45 1345 13 45 (13.4 334 34 3.3 vs 1144 11 44 11.4 256 56 2.56 4115 115 4.115 0.001. 0001 0.001 . 001 0.001) 1166 66 11.6 362 62 3.6 1004 10 04 10.0 313 3.13 2918 918 2.918 0.004 0004 004 1663 16 63 16.6 545 5.4 1443 14 43 14.4 452 52 4.52 2690 690 2.690 0.008 0008 008 1342 42 13.4 474 4.7 1114 11.1 368 68 3.68 3292 292 3.292 Thus 12.86 1286 12 86 (12.8 629 6 29 6.2 1387 87 13.8 314 3.14 1204 204 1.204 0.236. 0236 0.236 236 0.236) Additionally r 0096 096 0.096 0.434, 0434 0.434 434 0.434) THI (THI 0056 056 −0.056 0.648. 0648 0.648 648 0.648) patients 18 02 0.2 0. 134 (13. 33 3. 114 11. 2.5 411 4.11 000 0.00 00 116 36 100 10. 31 3.1 291 91 2.91 166 16. 54 5. 144 14. 4.5 269 69 2.69 13. 47 111 329 3.29 12.8 128 (12. 6. 138 120 20 1.20 023 0.23 23 009 09 0.09 043 0.43 005 −0.05 064 0.64 64 (13 2. 41 4.1 0.0 9 2.9 26 2.6 32 3.2 12. (12 1.2 0.4 −0.0 06 0.6 (1 1. −0. ( −0 −

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using “Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence”. MicroRNA29a3p MicroRNAap MicroRNA 29a 3p p cancers unclear microRNA29a3p microRNAap microRNA 4 201 collected years probe factors recurrentmetastasis, recurrentmetastasis recurrent metastasis, metastasis studied Ki Ki6 Ecadherin E cadherin noncancer non red vessels, vessels , vessels) followup follow size Tstage, Tstage T stage, stage T-stage differentiation p< (p 0.05. 005 0.05 . 0 05 0.05) Ecadherin. cadherin. Moreover miRNA29a3p+Ki67+Ecadherin miRNA29a3pKi67Ecadherin miRNAapKiEcadherin miRNA 3p+Ki67+E indexes invasion Oxford EvidenceBased Evidence Based Evidence. Evidence” 20 00 0.0 miRNA29a3p pKi 3pKi67E pKiE 2 0. miRNAap

Abstract Burley tobacco-leaf protein extracted by alkali and precipitated by acid was hydrolyzed enzymatically, and optimum protease and hydrolysis parameters were determined. Pepsin was best and gave the highest hydrolysis rate (15.55%). As per results of the single-factor test, optimum hydrolysis conditions were: temperature 37 °C, pH 2, and an [E]/[S] ratio of 5%. These hydrolysis conditions were optimized by an orthogonal experiment that rendered the same results as the single factor experiment. The ratio of essential to total amino acids and that of essential to non-essential amino acids contained in the burley tobacco-leaf protease hydrolysate were higher than the FAO/WHO standard values of 0.4 and 0.6, among which hydrophobic amino acid content was the highest, followed by negatively and positively charged amino acid contents. In vitro antioxidant experiments showed that the scavenging rates of DPPH, superoxide anion, and hydroxyl radicals of tobacco-leaf protein hydrolysates were higher than those before hydrolysis. Further, the hydroxyl radical-scavenging rate was the most significant, and total antioxidant capacity was improved. The nutritive value of the burley tobacco-leaf protein hydrolysate improved upon pepsin-mediated hydrolysis, and the antioxidant activity was better. These results provide a theoretical basis for further development and utilization of tobacco protein resources.

Abstract Despite the use of Maillard reaction products (MRPs) as food flavoring and coloring agents, they are also known to constitute acrylamide, heterocyclic amines, advanced glycosylation end products, and precursors of low molecular weight compounds. The very little is known about the toxicology of peony seed meal-derived MRPs. In this study, sub-chronic toxicity of peony seed meal derived MRPs was evaluated in Sprage-Dawley (SD) rats. Results showed that the body weight, hematology and serum biochemistry, organ coefficient and histopathology of SD rats with daily intake of peony seed meal-derived MRPs lower than 0.45 g/kg were not affected. After feeding with peony seed meal-derived MRPs for 13-weeks, there were no significant toxic effect on either male or female rats. This study provides a theoretical basis for the safety of MRPs derived from the reactants of enzymatic hydrolysis of peony seed meal.

This study evaluated the effects of perioperative nutrition management by a multidisciplinary team on nutrition and postoperative complications of patients with esophageal cancer. A total of 239 patients with esophageal cancer who underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between February 2019 and February 2020 were included in the study. They were divided into the experimental group (120 patients) and the control group (119 patients) using the random number table method. Control group patients received routine diet management and experimental group patients received perioperative nutrition management by a multidisciplinary team. The differences of nutriture and postoperative complications between the two groups were compared. At 3 and 7 days after surgery, the experimental group patients had higher total protein and albumin levels (P<0.05), shorter postoperative anal exhaust time (P<0.05), lower incidence of postoperative gastrointestinal adverse reactions, pneumonia, anastomotic fistula, hypoproteinemia (P<0.05), and lower hospitalization costs (P<0.05) than the control group. Nutrition management by a multidisciplinary team effectively improved the nutriture of patients, promoted the rapid recovery of postoperative gastrointestinal function, reduced postoperative complications, and reduced hospitalization costs. 23 201 202 120 (12 119 (11 method compared surgery P<0.05, P005 P P<0.05 , 0 05 reactions pneumonia fistula (P<0.05 function 2 20 12 (1 11 P00 P<0.0 (P<0.0 1 ( P0 P<0. (P<0. P<0 (P<0 P< (P< (P

Abstract Fruits will be subjected inevitably to various external forces in the process of harvesting, transportation, processing, and storage, which will cause mechanical damage. The research on mechanical properties and damage mechanisms of fruit can effectively control its loss. In this study, fruits are divided into different types according to their morphology and structure. The impact, vibration, static pressure, and other mechanical damage on fruits are studied. It is important to identify the damaged parts of fruit after damage quickly and accurately. Therefore, this study analyzes the application of nondestructive testing technologies such as spectral detection technology, NMR (nuclear magnetic resonance) detection technology, and acoustic and electrical characteristics detection technology in fruit damage detection. harvesting transportation processing storage loss structure impact vibration pressure studied accurately Therefore nuclear resonance

Abstract Objectives Pain is associated with many circumstances, including inflammatory reactions, which arise from modification of the features of signaling pathways. α2-adrenergic receptor antagonists are widely utilized in narcosis. Here, the authors focused on the narcotic effect of A-80426 (A8) on Complete Freund's Adjuvant (CFA) injections-triggered chronic inflammation pain in WT and TRPV1-/- mice and explored whether its antinociceptive impact was modulated via Transient Receptor Potential Vanilloid 1 (TRPV1). Method CFA with or without A8 was co-administered to the mice, which were categorized randomly into four groups: CFA, A8, control, and vehicle. Pain behaviors underwent evaluation through mechanical withdrawal threshold, abdominal withdrawal reflex, and thermal withdrawal latency of WT animals. Results Quantitative polymerase chain reaction revealed that inflammation-promoting cytokines (IL-1β, IL-6, and TNF-α) were upregulated in Dorsal Root Ganglion (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT animals. A8 administration reduced the pain behaviors and production of pro-inflammatory cytokines; however, this effect was significantly reduced in TRPV1-/- mice. Further analysis showed that CFA treatment reduced the TRPV1 expression in WT mice and A8 administration increased its expression and activity. The co-administration of SB-705498, a TRPV1 blocker, did not influence the pain behaviors and inflammation cytokines in CFA WT mice; however, SB-705498 the effect of A8 in WT mice. In addition, the TRPV1 block decreased the NFκB and PI3K activation in the Dorsal Root Ganglia (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT mice. Conclusions Together, A8 exerted a narcotic impact on CFA-supplemented mice via the TRPV1-modulated NFκB and PI3K pathway. circumstances reactions pathways α2adrenergic αadrenergic α2 adrenergic α narcosis Here A80426 A 80426 A-8042 (A8 Freunds Freund s (CFA injectionstriggered injections triggered TRPV1/ TRPV / TRPV1-/ TRPV1. . (TRPV1) coadministered co administered groups control vehicle threshold reflex animals inflammationpromoting promoting IL1β, IL1β ILβ IL 1β, 1β β (IL-1β IL6, IL6 6, 6 IL-6 TNFα TNF TNF-α DRG (DRG SCDH (SCDH proinflammatory pro however activity coadministration SB705498, SB705498 SB 705498, 705498 blocker SB-70549 addition PIK PI K Together CFAsupplemented supplemented TRPV1modulated TRPVmodulated pathway A8042 8042 A-804 (A TRPV1- (TRPV1 IL- SB70549 70549 SB-7054 A804 804 A-80 (TRPV SB7054 7054 SB-705 A80 80 A-8 SB705 705 SB-70 8 A- SB70 70 SB-7 SB7 7 SB-

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR. (CDDPs ischemiareperfusion ischemia reperfusion (IR years However explored Here SpragueDawley Sprague Dawley model echocardiography microscopy techniques adenoassociated adeno associated autophagy Meanwhile LC3B LCB LC B p62 p autolysosomes Moreover Furthermore AMPKmTOR AMPK mTOR Herein p6

Abstract Chemotherapy is the main treatment option for advanced osteosarcoma, which is the most common type of primary bone malignancy. However, patients develop resistance rapidly and many succumb to the disease. Niclosamide, an anthelmintic drug, has been recently identified to display potent and selective anti-cancer activity. In this work, we show that niclosamide at sub-micromolar concentrations inhibits proliferation and migration, and induces apoptosis in both parental and chemo-resistant osteosarcoma cells, with much less toxicity in normal osteoblastic cells. Interestingly, chemo-resistant osteosarcoma cells are more sensitive to niclosamide compared to parental cells. We further identify that inhibition of β-catenin is the underlying mechanism of niclosamide’s action in osteosarcoma cells. In addition, we reveal that chemo-resistant osteosarcoma cells display increased β-catenin activity compared to parental cells, which might explain the hypersensitivity of chemo-resistant cells to niclosamide. Our work provides pre-clinical evidence that niclosamide can be repurposed for treating osteosarcoma. Our findings also suggest the therapeutic value of β-catenin to overcome osteosarcoma chemo-resistance. malignancy However disease Niclosamide drug anticancer anti cancer submicromolar sub micromolar migration chemoresistant chemo resistant Interestingly βcatenin β catenin niclosamides s addition preclinical pre clinical chemoresistance. chemoresistance resistance. chemo-resistance

Abstract Hydrogen sulfide (H2S) is recognized for its beneficial role in postharvest fruit and vegetable preservation. Postharvest goji berries are easy to mildew and rot which reduce the nutritional value, flavor, and shelf life. Hydrogen sulfide treatment could improve the quality attributes of postharvest goji berry (Lycium barbarum L.); however, it is not clear that the effects of H2S at the transcriptional level in postharvest goji berries. Our data revealed that the differentially expressed genes (DEGs) of fresh goji fruits after H2S treatment were different with different storage time. There were 523 DEGs in the three comparison groups after H2S treatment on the 2nd, 4th and 6th day of storage. In the pathway of KEGG metabolic function, most of the DEGs were conserved in carbohydrate metabolism, secondary metabolites biosynthesis, amino acid metabolism, lipid metabolism, energy metabolism, the metabolic pathways of terpenoids and polyketones. The genes in the phenylpropanoid biosynthesis, flavonoid biosynthesis, starch, and sucrose metabolism pathway were selected and validated by quantitative real-time PCR (qRT-PCR). Our results provide insights into the effect of H2S on postharvest goji berries at the transcriptional level and provide the basis for application of H2S as gas regulator for preservation of goji berry. HS H S (H2S value flavor life Lycium L. L L.) however (DEGs time 52 2nd nd th function biosynthesis polyketones starch realtime real qRTPCR. qRTPCR qRT . (qRT-PCR) 5 (qRT-PCR

Abstract Background Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. Results We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3’ splice site (Alt3’SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. Conclusion Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.