Abstract Background Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. Results In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. Conclusions Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis. failed However unknown study BMP2induced BMPinduced BMP2 induced BMP model (MSCs competition process nuclearcytoplasmic nuclear cytoplasmic nuclearlocalized localized YAP5SA YAPSA 5SA SA Furthermore DKK1 DKK Thus

Abstract Objective The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. Methods Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. Results The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p= 0.063), 87.9% vs. 76.3% (p< 0.001), 78.5% vs. 58.5% (p< 0.001) and 86.3% vs. 66.7% (p< 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p= 0.034), DFS (p= 0.002) and OS (p= 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p= 0.025. Conclusions PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidence III.

RESUMO: Com a transferência gradual de enorme força de trabalho jovem e de meia idade do campo agrícola para os setores não agrícolas, o papel negativo da fragmentação da terra (LF), relacionada à segurança alimentar, está cada vez mais refletido no processo de modernização agrícola. Enquanto isso, os papéis positivos da lavoura combinada dos agricultores na produção estão surgindo gradualmente. Com base no histórico acima, o objetivo deste estudo é explicar a relação entre o plantio direto dos agricultores, LF e eficiência da produção agrícola (APE). O estudo usou dados do levantamento e o modelo SFA-QR para investigar empiricamente os efeitos da FL e do plantio direto dos agricultores sobre o APE. Além disso, este artigo analisou o efeito moderador do plantio combinado dos agricultores na relação entre LF e APE. Os resultados demonstram que: (1) A lavoura combinada dos agricultores melhora significativamente o APE, especialmente em domicílios de baixa e média eficiência; (2) LF tem um impacto negativo na APE, especialmente em domicílios de baixa e média eficiência; (3) A lavoura combinada pode aliviar os efeitos adversos do LF no APE. Nesse sentido, o trabalho também propõe algumas sugestões para enfrentar os efeitos adversos da FL e promover o plantio combinado dos agricultores na produção.

ABSTRACT: With the gradual transfer of an enormous young and middle age labor force from agricultural field to non-agricultural sectors, the negative role of land fragmentation (LF), which is related to food security, is increasingly reflecting in the process of agricultural modernization. Meanwhile, the positive roles of farmers’ combined-tillage in production are gradually emerging. Based on the above background, this study explained the relationship among farmers’ combined-tillage, LF and agricultural production efficiency (APE). The study used survey date and the SFA-QR model to empirically investigate the effects of LF and farmers’ combined-tillage on APE. Furthermore, this article analyzed the moderating effect of farmers’ combined-tillage on the relationship between LF and APE. The results demonstrated that: (1) Farmers combined-tillage improves the APE significantly, especially on low and medium efficiency households; (2) LF has a negative impact on APE, especially on low and medium efficiency households; (3) Combined-tillage could alleviate the adverse effects of LF on APE. In this regard, the paper also proposed some suggestions to face the adverse effects of LF and promote farmers’ combined-tillage in production.

Abstract Impacts of high hydrostatic pressure (HHP) pretreatment on the physicochemical, functional and antioxidant properties of soybean protein isolate (SPI) were investigated. Changes in the secondary and tertiary structures were determined by Fourier transform infrared spectra and fluorescence spectra. The particle sizes reduced from 217.20 nm to 192.70 nm while the zeta potential increased. It’s revealed by scanning electron microscopy that the HHP treatment could result in the formation of large aggregation, leaving the SPI with irregular and uneven surface. Moreover, hollow spheres were also observed in SPI by means of dynamic and static light scattering. As a result, the foaming capacity of HHP-treated SPI and antioxidant activity of the HHP-treated SPI hydrolysates were improved significantly.

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials.

ABSTRACT The objective of this study was to identify differentially expressed genes (DEG) between females and males in early bovine embryos. Superovulated cattle (n = 4) in the age span of 16–18 months were artificially inseminated with semen from the same bull that has been proven to be fertile. Blastocysts were collected by routine non-surgical uterine flushing on day 7 after insemination. This study determines the sex of embryos using a micro-injection pipette to collect a few blastomeres through the Zona pellucida. The remaining blastomeres were used for single-cell RNA sequencing (scRNA-seq) analysis on the Illumina platform, followed by differential expression analysis, Gene Ontology (GO) function analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The criteria for identifying DEG will be set at |log2(Fold change)| ≥ 1 and P<0.05. A total of 8004 DEG were detected in female (Denoted as BLX, n = 3) and male (Denoted as BLY, n = 3) blastocysts. Transcripts highly expressed in the female embryos were related to catalytic activity, nucleotide binding, and catabolic process, while transcripts highly expressed in the male embryos were linked to oxidative phosphorylation, mitochondrion, and the ribosome. Nine genes that may be involved in blastocyst growth and development were screened, suggesting that their differential expression may be responsible for the differences in the development of male and female embryos. This study provides important information on potential genes and pathways associated with differences in early female and male embryonic development.

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2–4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0–56.0) years old and disease duration of 12.0 (6.0–12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Abstract Objectives The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. Methods MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β TNF- α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. Results For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of 1-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. Conclusions All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.

Abstract Fibrolipomatous hamartoma (FLH) of the nerve, also known as lipomatosis of the nerve, neurofibrillary lipomatous lesion, or intraneural lipoma, is a rare benign soft tissue tumor which mainly occurs in the nerves of the upper limb, especially in the median nerve. In April 2021, a 30-year-old male patient was secondly admitted to our hospital and underwent his third surgery, due to the recurrence of a mass and pain in the right palm, noticeable swelling and numbness of the right index and ring fingers, and limited flexion and extension activities of the right ring finger. He first visited our hospital in December 2017 due to a mass and pain in the right palm and swelling and numbness of the right index and ring fingers. When the clinician asked for the patient medical history, his parents stated that his right middle finger was swollen after birth. When the patient was ten years old; he was diagnosed with “macrodactyly” at the local county hospital, not in our hospital, and subsequently, the middle finger was amputated at the metacarpophalangeal joint level at the local county hospital. The postoperative pathological examination was not performed at that time, which was the first surgery the patient received. FLH is clinically rare, and its exact epidemiology and etiology are poorly understood. FLH is highly suspected in cases where a painless mass is present in the wrist, combined with macrodactyly. Magnetic resonance imaging and pathological examination are helpful in clarifying the diagnosis. Although FLH is a benign tumor, an individual treatment plan is the best choice according to the severity of the patient’s symptoms. Therefore, further exploration and understanding of this disease by clinicians radiologists, and pathologists is necessary.

Resumen El hamartoma fibrolipomatoso (FLH) del nervio, también conocido como lipomatosis del nervio, lesión neurofibrilar lipomatosa, o lipointraneural, es un tumor benigno de tejido blando poco frecuente, que se presenta principalmente en los nervios del miembro superior, especialmente en el nervio mediano. En abril de 2021, un paciente masculino de 30 años fue ingresado por segunda vez en nuestro hospital y sometido a su tercera cirugía debido a la recurrencia de una masa y dolor en la palma derecha, evidente hinchazón y entumecimiento de los dedos índice y anular derecho y limitadas actividades de flexión y extensión del dedo anular derecho. En diciembre de 2017, visitó por primera vez nuestro hospital debido a una masa y dolor en la palma derecha, y a la hinchazón y entumecimiento de los dedos índice y anular derecho. Cuando el clínico preguntó la historia clínica del paciente, sus padres declararon que su dedo medio derecho estaba hinchado después del nacimiento, y cuando el paciente tenía 10 años, fue diagnosticado con “macrodactilia” en el hospital local del condado, no en nuestro hospital Posteriormente, el dedo medio fue amputado a nivel de la articulación metacarpofalángica en el hospital comarcal local, pero no se realizó la patología postoperatoria en ese momento, siendo ésta la primera cirugía a la cual se sometió el paciente. La FLH es clínicamente rara, y su epidemiología y etiología exactas no se entienden bien. En los casos que presentan una masa indolora en la muñeca, combinada con macrodactilia, se sospecha de FLH. La resonancia magnética y la patología son útiles para aclarar el diagnóstico. Aunque la FLH es un tumor benigno, el plan de tratamiento individual es la mejor opción de acuerdo con la gravedad de los síntomas del paciente. Por lo tanto, es necesaria una mayor exploración y comprensión de esta enfermedad por parte de médicos, radiólogos y patólogos.

The fluorescent microspheres are prepared by the swelling-evaporation method. The optimal swelling conditions are obtained by researching related factors, such as types and dosages of swelling agent, dosages of fluorescent substance, swelling time and swelling temperature. Considering that the structure of microspheres can influence the swelling properties, the paper mainly focuses on the effect of molecular weight and surface carboxyl group content of polystyrene microspheres on swelling properties. When the molecular weight of microspheres is 75276 g mol-1, the density of carboxyl group on their surface is 6.94×10-4 mol g-1, and the doping amount of europium complex reaches the maximum of 24.9 mg g-1 with the strongest fluorescence intensity. Meanwhile, the as-prepared fluorescent microspheres have high monodispersity, uniform particles size and high thermal stability (the decomposition temperature is 385oC), which sets up the good foundation for biomolecule detection. So, this work provides a significant experience for the preparation of fluorescent microspheres.

Abstract A modified QuEChERS method coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of eight biogenic amines (BAs) in Xinjiang smoked horsemeat sausages. The conditions of UPLC-MS/MS, extraction solvent and QuEChERS purification were optimized. The internal standard method was used for quantitative analysis. Results showed that the eight BAs exhibited good linearity (1-200 μg/L, correlation coefficient > 0.99). The limits of detection and quantification were 5 μg/kg and 10 μg/kg, respectively. The accuracy was between 80.4% and 111.4%, and the precision was less than 10%. The established method was effectively used for the determination of eight BAs in forty Xinjiang smoked horsemeat sausages. Results showed that tyramine was the major amine, followed by cadaverine, putrescine and spermine. Total BAs content ranged from 26.5 mg/kg to 352.9 mg/kg, the contents of BAs in Xinjiang smoked horsemeat sausages may pose a potential health risk.

Abstract Tea polyphenols are one of the most important ingredients in Qingzhuan tea. Usually, a chemical method is used to determine tea polyphenols content, but it was time-consuming and laborious. This paper attempted to use near infrared spectroscopy (NIRS) technology combined with three partial least squares methods to predict tea polyphenols content quickly and nondestructively. The partial least squares (PLS), synergy interval PLS (siPLS) and genetic algorithm based PLS (gaPLS) were used to establish prediction models, the performance of the final model was showed by root mean square error of prediction (RMSEP) and determination coefficient (Rp2) in prediction set. The best spectral preprocessing method was multivariate scattering correction (MSC); the RMSEP and Rp2 of PLS model were 0.145% and 0.8974, respectively; the siPLS model was established with four spectral regions (4377.6 cm-1-4751.7 cm-1, 4755.6 cm-1-5129.7 cm-1, 6262.7 cm-1-6633.9 cm-1 and 7386 cm-1-7756.3 cm-1), whose RMSEP and Rp2 were 0.0652% and 0.9235, respectively; the gaPLS model was established with 36 spectra dada points and showed the best performance (RMSEP=0.0624%, Rp2=0.9769) compared with the PLS and si-PLS models. Therefore, the application of near infrared technology combined with the gaPLS method could predict tea polyphenols content in Qingzhuan tea more accurately and rapidly.

ABSTRACT Purpose: This study aimed to develop a minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach using a canine model. Methods: Six Alaskan dogs were used for developing the surgical approach. The bilateral laminae of C3-7 were cut with an ultrasonic osteotome and fixed with bilateral plates to maintain the lamina lifting and reshape a wider spinal canal. The important structures, such as ligaments, supraspinous ligaments, interspinous ligaments, and ligamentum flavum were preserved. The therapeutic effect was evaluated by preoperative and postoperative imaging results and neck mobility. Results: The surgical procedures were all successfully performed in the 6 animals. All the dogs survived well within 1 year of postoperative follow-up. The postoperative neck mobility was as good as the preoperative one. Computed tomography results showed that the anteroposterior diameter of the spinal canal was successfully enlarged and maintained well. Conclusions: The minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach was feasible in a canine model, which might be applied in clinical practice.

Abstract Enteromorpha prolifera polysaccharide (EP) is a water-soluble sulfated polysaccharide with many types of biological activities. In this study, the crude polysaccharide was extracted from Enteromorpha prolifera and degraded by different physical, chemical, and biological methods. The results showed that the enzymatic degradation products displayed the best tyrosinase inhibitory activity. The optimal enzymatic degradation conditions were as follows: 30 °C, pH 5.5, 750 U/mL enzyme dosage for 2 h. The enzymatic hydrolysates were then divided into six EP fractions (EPFs) by an ultrafiltration membrane. The in vitro tyrosinase inhibitory activity of these fractions showed that the smaller the molecular weight of EPF, the better the inhibitory effect on tyrosinase. The antioxidant and tyrosinase inhibitory effect of the most effective EPF, a molecular weight below 5 kDa, (EPF5), was further confirmed on B16 cells. A kinetic study of tyrosinase inhibitory activity revealed that EPF5 is a competitive-uncompetitive mixed-type inhibitor of tyrosinase. These findings suggested that EPF5 has significant potential as a skin-whitening agent in cosmetics as well as an antibrowning agent in the food and agriculture industries.