Search

The Ru-catalyzed carbonylation of alkenes with CO2 as a C1 surrogate and imidazole chlorides as the promotor is investigated by a combination of computational and experimental study. The conversion rate of CO2 to CO is positively correlated with the efficiency of both hydroesterification and hydroformylation, which is found facilitated in the presence of chloride additives with a decreasing order of BmimCl ∼ B3MimCl > BmmimCl ∼ LiCl. Taking the hydroesterification with MeOH as a representative example, BmimCl bearing C–H functionality at the C2 site of the cation assists the reduction of CO2 to CO as a hydrogen donor medium, with the anion and cation acting in a synergistic fashion. Subsequent insertion of CO2 into the formed Ru–H bond with the assistance of chloride anion produces the Ru–COOH species, which ultimately accelerates the activation of CO2.

Nonalcoholic fatty liver disease (NAFLD) is a kind of serious fat disorder that has become a critical problem to human society. Therefore, finding drugs that are safe and effective has become more and more important. Erythritol (Ery) is a polyol sweetener with a variety of biological functions. However, whether Ery has a relieving effect on NAFLD has not been reported yet. Therefore, we induced HepG2 cells with oleic acid and palmitic acid as our in vitro model. Moreover, we choose wild-type mice with tyloxapol and high-fat diet and nuclear factor E2-related factor 2 (Nrf2) knockout mice with high-fat diet as our in vivo model. We found that Ery could reverse the lipid accumulation, oxidative stress, and endoplasmic reticulum stress caused by the NAFLD model. The mechanism studies showed that Ery promoted the translocation of Nrf2 from cytoplasm to nucleus, and the molecular simulation docking results of Ery and Nrf2 showed that there was a hydrogen bond between them. Moreover, Ery could promote the production of HO-1 and NQO1 antioxidant proteins and inhibit the expression of endoplasmic reticulum stress proteins GPR78, p-PERK, and CHOP. On the contrast, when Nrf2 was knocked out in mice, Ery lost its protective effect on NAFLD. In conclusion, we found that the potential mechanism of Ery's protective effect is that it plays an antioxidant role by activating the Nrf2 signaling pathway, thereby inhibiting endoplasmic reticulum stress and lipid accumulation in NAFLD.

Jian-Guo Chen,1,2 Jian Zhu,1 Yong-Hui Zhang,1 Yong-Sheng Chen,1 Lu-Lu Ding,1 Hai-Zhen Chen,2 Ai-Guo Shen,2 Gao-Ren Wang2 1Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, People’s Republic of China; 2Cancer Institute, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, People’s Republic of ChinaCorrespondence: Jian-Guo Chen Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University; Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, People’s Republic of China Email chenjg@ntu.edu.cnBackground and Aims: To explore the long-term trend of liver cancer survival, based on the real-world data (RWD) in the past 45 years from a population-based cancer registry, in Qidong, China.Methods: A number of 32,556 patients with liver cancer were registered during the period of 1972 to 2016. Mixed methods by active and passive follow-up were performed. Life table method was employed for survival analysis by SPSS22 software. Wilcoxon (Gehan) statistics was considered as a significant test. Relative survival was calculated by using SURV software, and its annual percent change (APC) was estimated by the Joinpoint Regression Program.Results: The overall observed survival (OS) rates of 1-, 5-, 10-, and 20-year rates from the data series were 18.51%, 6.28%, 4.03%, and 2.84%, and their relative survival (RS) rates were 18.88%, 6.95%, 4.96%, and 4.49%, respectively. For 24,338 male cases, the 5-year OS and RS rates were 5.93% and 6.54%, and for 8218 female cases, 7.34% and 8.15%, respectively, with P values less than 0.01. Survival rates of liver cancer from three 15-year periods of 1972– 1986, 1987– 2001, and 2002– 2016 have increased significantly, with 5-year OS rates of 2.02%, 4.40%, and 10.76%, 5-year RS rates of 2.18%, 4.83%, and 12.18%; 10-year OS and RS rates of 0.95%, 3.00%, and 7.02%, vs 1.13%, 3.65%, and 8.96%, respectively, showing a very significant upward trend (P< 0.01). There are significant differences among age groups (P< 0.01): those aged 55– 64 demonstrated the best OS and RS rates of 5-year, being 8.44% and 9.09%, respectively.Conclusion: There are significant gender and age differences in the survival rate of liver cancer in Qidong. RWD indicates the relative lower survival rate of liver cancer in this area, but great improvement has been achieved over the past decades.Keywords: liver cancer, survival rate, long-term trend, real-world data, Qidong

Introduction: Fungemia in preterm infants results in high mortality and morbidity. The genotypes, drug susceptibilities of Candida pelliculosa strains, and clinical features of two outbreaks of neonatal candidemia caused by C. pelliculosa were analyzed, in order to provide evidence for the outbreaks and characteristics of C. pelliculosa neonatal candidemia. Methodology: The strains were genotyped by pulsed-field gel electrophoresis to investigate their genetic relatedness. The broth microdilution method was used to determine in vitro susceptibility of the isolates to antifungal drugs. Clinical features of the infected patients were collected to analyze the risks for C. pelliculosa infection. Results: Fourteen neonates, hospitalized in the neonatal intensive care unit from November 2012 to October 2013, were infected by C. pelliculosa. All 14 patients were cured after treatment with fluconazole and discharged without any complications. The C. pelliculosa isolates from the 14 patients were clustered into two groups, indicating that the outbreaks were caused by two types of strains. Eight of nine strains isolated from the 2013 outbreak were clustered into the same group, while one isolate was grouped together with five isolates from the 2012 outbreak. In vitro experiments demonstrated high antifungal activity of fluconazole, voriconazole, amphotericin B, and 5-fluorocytosine to C. pelliculosa. The common symptoms of C. pelliculosa candidaemia were fever, cyanosis, polypnea, hypoactivity, and apnea. Conclusions: The current study revealed high in vitro susceptibility of C. pelliculosa to antifungals. As C. pelliculosa candidaemia cannot be characterized by clinical symptoms and routine blood testing alone, monitoring unusual strains isolated from immunodeficient hosts is very important to prevent possible outbreaks.

The two-component Cry48Aa/Cry49Aa toxin produced by Lysinibacillus sphaericus shows specifically toxic to Culex quinquefasciatus mosquito larvae. Cry49Aa C-terminal domain is responsible for specific binding to the larval gut cell membrane, while its N-terminal domain is required for interaction with Cry48Aa. To investigate functional role of cysteine in Cry49Aa, four cysteine residues at positions 70, 91, 183, and 258 were substituted by alanine. All mutants showed similar crystalline morphology and comparable yield to that of the wild type except that the yield of the C91A mutant was low. These cysteine residues did not involve in disulfide bond formation within or between Cry49Aa molecules. Cys91, Cys183 and Cys258 are essential for toxicity against C. quinquefasciatus larvae, while Cys70 is not. Substitution at C91, C183 and C258 caused weak Cry48Aa- Cry49Aa interaction, while mutations at C183 and C258 reduced the binding capacities to the larval gut cell membrane. Thus, Cysteine residues at position 91, 183 and 258 in Cry49Aa are required for full toxicity of Cry48Aa/Cry49Aa toxin.

Autophagy has been proved to play a vital role in cardiac hypertrophy. The present study was designed to investigate the relationship between miR-100-5p and autophagy in the development of cardiac hypertrophy. Here, miR-100-5p expression was detected in abdominal aortic coarctation (AAC)-induced cardiac hypertrophy rats and Angiotensin II (Ang II)-stimulated cardiomyocytes. In vitro and in vivo experiments were performed to explore the function of miR-100-5p on autophagy and cardiac hypertrophy. We also investigated the mechanism of miR-100-5p on autophagy with dual-luciferase reporter assays, RNA immunoprecipitation (RIP), quantitative real-time PCR (qRT-PCR), western blot, immunofluorescence, and transmission electron microscopy (TEM). The results showed that miR-100-5p was highly expressed in hypertrophic hearts and Ang II-induced cardiomyocytes. Overexpression of miR-100-5p promoted the expression of cardiac hypertrophy markers ANP, BNP and β-MHC and cell surface area, while those were suppressed by miR-100-5p inhibitor. Knockdown of miR-100-5p by antagomiR significantly improves cardiac function and attenuate cardiac hypertrophy in vivo. Mechanistic investigation has found that miR-100-5p promote autophagy by targeting mTOR. Inhibition of autophagy by 3-methyladenine (3-MA) or mTOR overexpression could reverse the function of miR-100-5p in cardiac hypertrophy. These results elucidate that miR-100-5p promoted the pathogenesis of cardiac hypertrophy through autophagy activation by targeting mTOR.

Recent studies suggest that astrocytes released a great quantity of extracellular vesicles (AEVs) to communicate with other brain cells. Under pathological conditions, AEVs are widely associated with the pathogenesis of neurobiological diseases by horizontally transferring pathogenic factors to neighboring cells or peripheral immune cells. Their beneficial role is also evident by the fact that they are involved in neuroprotection and neuroregeneration through alleviating apoptosis, maintaining neuronal function, and repairing neural injuries. The strong association of AEVswith neurological disorders makes AEVs a promising target for disease diagnosis, treatment, and prevention. The identification of disease-specific cargos in AEVs isolated from the patients' biofluids suggests AEVs as an attractive platform for biomarker development. Furthermore, the inhibition of inflammatory/toxic AEV release and the preservation of neuroprotective AEV release have been considered as potential therapeutic strategies in CNS disorder treatment and prevention, respectively. Here, we summarize the biological roles of AEVs as pathological contributors, protective/regenerative factors, and potential diagnostic biomarkers and therapeutic targets for neurological disorders, with a focus on recent progresses and emerging concepts.

In laboratory study environments, dialogue-videos, or videos of a tutor and a tutee solving problems together, have been shown to more effectively improve student learning than monologue-videos, or videos of tutors solving problems alone. Yet, few studies have replicated these findings in the context of authentic university classrooms. Here, we investigate the impact of dialogue-videos, and more specifically the effect of errors made by tutees in dialogue-videos, on student learning in the context of an undergraduate biology course. To understand why, we investigated students’ effort spent on watching videos, perceived influence of dialogue-videos, and worksheet completion rates. We found that higher-performing students perceived that they used the dialogue-videos to review content. We also found that higher-performing, but not lower-performing, students learned better from dialogue videos where tutees made errors. We also discuss the complexities of replicating laboratory studies in the classroom and implications of our findings. Implications for practice or policy: Tutee errors can be intentionally included in dialogue-videos to promote student learning. When students lack the necessary prior knowledge, monologue-videos may be more effective in presenting the course content. When using dialogue-videos, instructors can encourage students to collaborate to resolve any confusion in time to maximise the benefit of dialogue-videos in teaching and learning.

The aim of this study was to evaluate the association of the chromobox homologue 7 (CBX7) expression with the epithelial–mesenchymal transition in cervical cancer (CC), as well as with the disease prognosis. CBX7, E-cadherin (E-cad), and vimentin (VIM) expression levels were detected with immunohistochemistry. The relationship between the expression of CBX7, E-cad, and VIM expression and conventional clinicopathological characteristics of CC were evaluated. The positive expression rates of CBX7 and E-cad in the CC tissues were lower than the adjacent non-tumorous cervical tissues. Moreover, the VIM expression level was higher. The CBX7 expression was positively correlated with the E-cad expression, whereas was negatively correlated with the VIM expression. Furthermore, CBX7 was associated with the disease clinical staging, histological differentiation, lymph node metastasis, and vascular invasion. Patients with negative CBX7 expression showed decreased overall survival rates compared with those with low or high CBX7 expression. Multivariate Cox regression analysis indicated that the decreased CBX7 expression was an independent predictor for the poor prognosis of CC. In conclusion, the absence of CBX7 is associated with the histologic differentiation, lymphatic metastasis, vascular invasion, and poor prognosis of CC. CBX7 may be an independent prognostic factor for the prognosis of CC patients.

S-phase kinase-associated protein 2 (Skp2) performs oncogenic functions in cancers; however, how Skp2 is regulated post-transcriptionally is elusive in osteosarcoma. Therefore, we determined whether miR-506 could directly target Skp2 in osteosarcoma to perform its tumor suppressive functions. Here, we found that miR-506 mimics suppressed cell viability, induced apoptosis, and attenuated migration and invasion in osteosarcoma cells. Moreover, upregulation of Skp2 accelerated cell viability and motility and rescued the tumor suppressive effect of miR-506 in osteosarcoma cells. Moreover, downregulation of Skp2 inhibited cell viability and decreased cell motility, which enhanced the antitumor activity induced by miR-506 mimic transfection in osteosarcoma cells. Our western blotting results implied that miR-506 inhibited Skp2 expression and subsequently upregulated Foxo1 and p57 in OS cells. In summary, miR-506 performs an anticancer activity via directly targeting Skp2 in osteosarcoma cells, indicating that inactivation of Skp2 by miR-506 might be an alternative strategy for treating osteosarcoma.

Aims Morphological abnormalities are present in patients with developmental dysplasia of the hip (DDH). We studied and compared the pelvic anatomy and morphology between the affected hemipelvis with the unaffected side in patients with unilateral Crowe type IV DDH using 3D imaging and analysis. Methods A total of 20 patients with unilateral Crowe-IV DDH were included in the study. The contralateral side was considered normal in all patients. A coordinate system based on the sacral base (SB) in a reconstructed pelvic model was established. The pelvic orientations (tilt, rotation, and obliquity) of the affected side were assessed by establishing a virtual anterior pelvic plane (APP). The bilateral coordinates of the anterior superior iliac spine (ASIS) and the centres of hip rotation were established, and parameters concerning size and volume were compared for both sides of the pelvis. Results The ASIS on the dislocated side was located inferiorly and anteriorly compared to the healthy side (coordinates on the y-axis and z-axis; p = 0.001; p = 0.031). The centre of hip rotation on the dislocated side was located inferiorly and medially compared to the healthy side (coordinates on the x-axis and the y-axis; p < 0.001; p = 0.003). The affected hemipelvis tilted anteriorly in the sagittal plane (mean 8.05° (SD 3.57°)), anteriorly rotated in the transverse plane (mean 3.31° (SD 1.41°)), and tilted obliquely and caudally in the coronal plane (mean 2.04° (SD 0.81°)) relative to the healthy hemipelvis. The affected hemipelvis was significantly smaller in the length, width, height, and volume than the healthy counterpart. (p = 0.014; p = 0.009; p = 0.035; p = 0.002). Conclusion Asymmetric abnormalities were identified on the affected hemipelvis in patients with the unilateral Crowe-IV DDH using 3D imaging techniques. Improved understanding of the morphological changes may influence the positioning of the acetabular component at THA. Acetabular component malpositioning errors caused by anterior tilt of the affected hemi pelvis and the abnormal position of the affected side centre of rotation should be considered by orthopaedic surgeons when undertaking THA in patients with Crowe-IV DDH. Cite this article: Bone Joint J 2020;102-B(10):1311–1318.

BACKGROUND Single incision plus one port left-side approach (SILS+1/L) totally laparoscopic distal gastrectomy (TLDG) is an emerging technique for the treatment of gastric cancer. Reduced port laparoscopic gastrectomy has a number of potential advantages for patients compared with conventional laparoscopic gastrectomy: relieving postoperative pain, shortening hospital stay and offering a better cosmetic outcome. Nevertheless, there are no previous reports on the use of SILS+1/L TLDG with uncut Roux-en-Y (uncut R-Y) reconstruction. AIM To investigate the initial feasibility of SILS+1/L TLDG with uncut Roux-en-Y digestive tract reconstruction (uncut R-Y reconstruction) to treat distal gastric cancer. METHODS A total of 21 patients who underwent SILS+1/L TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at The Second Hospital of Shandong University. Reconstructions were performed intracorporeally with 60 mm endoscopic linear stapler and 45 mm no-knife stapler. The clinicopathological characteristics, surgical details, postoperative short-term outcomes, postoperative follow-up upper gastrointestinal radiography findings and endoscopy results were analyzed retrospectively. RESULTS All SILS+1/L operations were performed by SILS+1/L TLDG successfully. The patient population included 13 men and 8 women with a mean age of 48.2 years (ranged from 40 years to 70 years) and median body mass index of 22.8 kg/m2. There were no conversions to open laparotomy, and no other port was placed. The mean operation time was 146 min (ranged 130-180 min), and the estimated mean blood loss was 54 mL (ranged 20-110 mL). The mean duration to flatus and discharge was 2.3 (ranged 1-3.5) and 7.3 (ranged 6-9) d, respectively. The mean number of retrieved lymph nodes was 42 (ranged 30-47). Two patients experienced mild postoperative complications, including surgical site infection (wound at the navel incision) and mild postoperative pancreatic fistula (grade A). Follow-up upper gastrointestinal radiography and endoscopy were carried out at 3 mo postoperatively. No patients experienced moderate or severe food stasis, alkaline gastritis or bile reflux during the follow-up period. No recanalization of the biliopancreatic limb was found. CONCLUSION SILS+1/L TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery.

Lu Ding, Yu-Hang Gao, Ye-Ran Li, Yi-Fan Huang, Xin-Yu Wang, Xin Qi Department of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Chang Chun, People’s Republic of ChinaCorrespondence: Xin QiDepartment of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Xinmin St 71, Chang Chun, People’s Republic of ChinaTel +8615843073202Fax +86043181875600Email qixindoc@163.comPurpose: This study was to evaluate the metabolic score for insulin resistance (METS-IR) in female knee osteoarthritis (KOA) patients in a Chinese population. The associations between METS-IR and adipokines, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were investigated.Patients and Methods: This study included 4686 women from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and 108 women who underwent arthroplasty of KOA at a university hospital. The clinical data were collected, and adipokines were evaluated. METS-IR was calculated in the KOA patients and compared with the national baseline. Logistic regression analyses were applied to explore the associations of METS-IR with adipokines, ESR, and CRP.Results: Receiver operating characteristic curve analysis of METS-IR and metabolic syndrome (MetS) in national baseline showed an area under the curve value of 0.851, with sensitivity of 0.777 and specificity of 0.772. The METS-IR of KOA was higher than the national baseline level (40.29 ± 6.98 vs 36.20 ± 8.50, P < 0.01), even after adjusting age. In addition, the METS-IR was higher in patients with KOA who had MetS than in those without metabolic syndrome (nMetS), even after adjusting body mass index (BMI). After adjusting for age and BMI, METS-IR was associated with CRP (OR 1.238, 95% confidence interval (CI) 1.088, 1.409, P < 0.01), ESR (OR 1.124, 95% CI 1.008, 1.254, P = 0.036), plasma leptin (OR 1.123, 95% CI 1.052, 1.199, P < 0.01), plasma resistin (OR 1.134, 95% CI 1.011, 1.271, P = 0.031), and plasma adiponectin (OR 0.865, 95% CI 0.771, 0.971, P = 0.014).Conclusion: METS-IR in female KOA was higher than that of the national baseline. The METS-IR was related to adipokine disorder and inflammatory activity. These findings suggest that METS-IR can be used to evaluate the degree of involvement of MetS in KOA.Keywords: knee osteoarthritis, metabolic syndrome, insulin resistance, metabolic score for insulin resistance

Purpose Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo. Materials and methods By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated. Results Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se. Conclusion The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.

Background With the increase in extremely low birth weight (ELBW) infants, their outcomes received special attention. However, in China, studies of the outcomes of ELBW infants are rare. Methods The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units were reviewed and analyzed. Results A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76–62.02%. The survival rate rose with increasing BW, the ascending level of regional economic development and specialist hospitals. The incidence of complications was neonatal respiratory distress syndrome (85.2%), bronchopulmonary dysplasia (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days), and the other died after the neonatal period. A total of 768 ELBW infants died after medical care withdrawal, with economic factors and expected outcome being important causes. Conclusion The number of ELBW infants is increasing in China, and the overall survival rate is still low but is improving steadily.

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p 0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p 0.0001). In different subgroups grouped according to age, hemoglobin (HGB), creatinine, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age65 years (p = 0.001), HGB100 g/L (p 0.001), elevated LDH (p = 0.001), and Ca (p = 0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.

Spinal cord injury (SCI) is a devastating central nervous system (CNS) disease with no satisfying therapies available. Mobilizing endogenous neural stem cells (NSCs) to trigger intrinsic regeneration exhibits promising potentials for SCI repair. However, neurogenesis from endogenous NSCs is extremely restricted in the non-neurogenic spinal cord after SCI. Accumulation of protein aggregates has been shown to impede quiescent NSCs activation and the subsequent neurogenesis. Here, we found that ubiquitin c-terminal hydrolase l-1 (UCHL1), a deubiquitinating enzyme, functioned to regulate NSCs activation and neurogenesis by reducing protein aggregations through ubiquitin-proteasome pathway (UPP) in vitro. Upregulation of UCHL1 in spinal cord NSCs of rats with complete transection SCI efficiently enhanced NSCs proliferation and neurogenesis, leading to significantly improved functional outcomes. Based on protein microarray analysis of cerebrospinal fluid (CSF), our results revealed that A1 reactive astrocytes acted to restrict NSCs neurogenesis by negatively regulating UCHL1-depentdent protein aggregates removal via the C3/Nrf2 signaling. Indeed, blockade of A1 astrocytes using neutralizing antibodies after SCI also led to NSCs activation, increased neurogenesis and remarkably enhanced motor function recovery. This study not only revealed a novel mechanism regulating NSCs-medicated neurogenesis in the spinal cord, but also provided new molecular targets for neural repair strategies after SCI. Graphical Abstract Highlights UCHL1 facilitates NSCs activation by clearing intracellular protein aggregates through ubiquitin-proteasome approach A1 reactive astrocytes result in down-regulation of UCHL1 to inhibit spinal NSCs activation by C3 after SCI Overexpression of UCHL1 or blockade of A1 astrocytes lead to NSCs activation and neurons formation to promote SCI repair via UCHL1-proteasome pathway

The direct reprogramming of somatic cells into induced neural progenitor cells (iNPCs) has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation. We previously reported that astrocyte-derived induced pluripotent stem cells (iPSCs) have more tendencies for neuronal differentiation than fibroblast-derived iPSCs. However, the differences of neurogenic potential between astrocyte-derived iNPCs (AiNPCs) and iNPCs from non-neural origins, such as fibroblast-derived iNPCs (FiNPCs), and the underlying mechanisms remain unclear. Our results suggested that AiNPCs exhibited higher differentiation efficiency, mobility and survival capacities, compared to FiNPCs. The whole transcriptome analysis revealed higher activities of TGFβ signaling in AiNPCs, versus FiNPCs, following a similar trend between astrocytes and fibroblasts. The higher neurogenic competence, migration ability, and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor LY2157299. Hence, our study demonstrates the difference between iNPCs generated from neural and non-neural cells, together with the underlying mechanisms, which, provides valuable information for donor cell selection in the reprogramming approach.

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that can lead to heart failure and eventually death. MicroRNAs (miRs) play essential roles during PAH progression; however, their exact mechanism of action remains unclear. Apelin is a small bioactive peptide with a key protective function in the pathogenesis of PAH mediated by binding to the APJ gene. The aim of the present study was to investigate the role of miR-335-3p in chronic normobaric hypoxia (CNH)-induced PAH in mice and the potential underlying regulatory mechanism. Adult male C57BL/6 mice were exposed to normoxia (~21% O2) or CNH (~10% O2, 23 h/d) for 5 weeks. MiR-335-3p was significantly increased in lung tissue of CNH-induced PAH mice. Blocking miR-335-3p attenuated CNH-induced PAH and alleviated pulmonary vascular remodeling. Bioinformatics analysis and luciferase reporter assay indicated that nuclear factor-kappa beta (NF-κB) acted as a transcriptional regulator upstream of miR-335-3p. Pyrrolidine dithiocarbamate treatment reversed the CNH-induced increase in miR-335-3p expression and diminished CNH-induced PAH. Moreover, p50-/- mice were resistant to CNH-induced PAH. Finally, APJ was identified as a direct targeting gene downstream of miR-335-3p, and pharmacological activation of APJ by its ligand apelin-13 reduced CNH-induced PAH and improved pulmonary vascular remodeling. Our results indicate that NF-κB-mediated transcriptional upregulation of miR-335-3p contributes to the inhibition of APJ and induction of PAH during hypoxia; hence, miR-335-3p could be a potential therapeutic target for hypoxic PAH.

Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d‐galactosamine (d‐GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/d‐GalN. CA can restrain mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor‐erythroid 2‐related factor 2 (Nrf2) pathway with increasing the level of AMP‐activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.

BACKGROUND Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF. METHODS AND MATERIALS The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot. RESULTS Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations. CONCLUSION These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF.

The chromobox protein homolog 7 (CBX7), one member of the polycomb group family, has been characterized mainly to play a tumor-suppressive role in human malignant neoplasias. Moreover, downregulation of CBX7 is correlated with poor prognosis and aggressiveness in a variety of human cancers. However, the biological functions and role of CBX7 in cervical cancer have not been elucidated. In the present study, we explore whether CBX7 exerts its tumor-suppressive function in cervical cancer. To achieve this goal, molecular approaches were used to upregulate the expression of CBX7 or downregulation of CBX7 in cervical cancer cell lines. We observed that overexpression of CBX7 inhibited cell growth and induced apoptosis in cervical cancer cells. CBX7 overexpression retarded cell migration and invasion in cervical cancer cells. In line with this, downregulation of CBX7 promoted cell growth and migration as well as invasion in cervical cancer cells. Our findings suggest that CBX7 might be a tumor suppressor and could be a potential target in cervical cancer. Keywords: cervical cancer, CBX7, cell proliferation, invasion, apoptosis, migration, E-cadherin, motility

Objective Multiple myeloma (MM) patients with bone destruction are difficult to restore, so it is of great clinical significance to further explore the factors affecting MM bone destruction. Methods and results This study retrospectively analyzed 419 cases with MM. Multiple linear regression analysis showed that those MM patients with a higher concentration of Ca2+ in serum, higher positive rate of CD138 immuno-phenotype and advanced in stage with 13q34 deletion in cytogenetics would be more prone to bone destruction, while total bile acid (TBA) and kappa chain isotope negatively correlated with bone destruction in MM patients. The Kaplan-Meier analysis indicated that Ca2+, serum β2-microglobulin (β2-MG), hemoglobin (HGB), creatinine (CREA), uric acid (UA) and age correlated with the survival of bone destruction in MM patients. Cox regression analysis further showed that the independent prognostic factors of β2-MG and CREA had a higher risk for early mortality in bone destruction patients. Moreover, an index was calculated based on β2-MG and globulin (GLB) to white blood cell (WBC) ratio to predict the poor survival of bone destruction patients. Conclusion We provide a novel marker to predict the prognosis of myeloma patients using routine examination method instead of bone marrow aspiration, and provide a reference for clinical evaluation.

Spinal root avulsion typically leads to massive motoneuron death and severe functional deficits of the target muscles. Multiple pathological factors such as severe neuron loss, induction of inhibitory molecules, and insufficient regeneration are responsible for the poor functional recovery. Leucine-rich repeat and immunoglobulin-like domain-containing Nogo receptor-interacting protein 1 (LINGO-1), a central nervous system (CNS)-specific transmembrane protein that is selectively expressed on neurons and oligodendrocytes, serves as a potent negative mediator of axonal regeneration and myelination in CNS injuries and diseases. Although accumulating evidence has demonstrated improvement in axonal regeneration and neurological functions by LINGO-1 antagonism in CNS damage, the possible effects of LINGO-1 in spinal root avulsion remain undiscovered. In this study, a LINGO-1 knockdown strategy using lentiviral vectors encoding LINGO-1 short hairpin interfering RNA (shRNA) delivered by the Pluronic F-127 (PF-127) hydrogel was described after brachial plexus avulsion (BPA). We provide evidence that following BPA and immediate reimplantation, transplantation of LINGO-1 shRNA lentiviral vectors encapsulated by PF-127 rescued the injured motoneurons, enhanced axonal outgrowth and myelination, rebuilt motor endplates, facilitated the reinnervation of terminal muscles, improved angiogenesis, and promoted recovery of avulsed forelimbs. Altogether, these data suggest that delivery of LINGO-1 shRNA by a gel scaffold is a potential therapeutic approach for root avulsion. Impact Statement In this study, we attempted transplantation of lentivirus (LV)/leucine-rich repeat and immunoglobulin-like domain-containing Nogo receptor-interacting protein 1 (LINGO-1)-short hairpin interfering RNA (shRNA) encapsulated by the Pluronic F-127 (PF-127) hydrogel into a brachial plexus avulsion (BPA)-reimplantation model. We found that administration of LV/LINGO-1 shRNA facilitates neuron survival and axonal regeneration, attenuates muscle atrophy and motor endplate (MEP) loss, enhances neovascularization, and promotes functional recovery in BPA rats. Co-transplantation of LV/LINGO-1 shRNA and gel reinforces the survival-promoting effect, axonal outgrowth, and angiogenesis in comparison with LV/LINGO-1 shRNA application alone. Our research provides evidence that LV /LINGO-1 shRNA delivered by PF-127 represents a new treatment strategy for BPA repair.

Background Extramedullary systems are commonly used in knee arthroplasty, with the rod location being determined from the tibial torsion line during surgery. The traditional method for tibial torsion measurement is not in accordance with clinical practice. This study aimed to evaluate proximal and distal tibial torsion using 3-dimensional (3D) computed technology to establish a new evaluation method, as well as to investigate the association between tibial torsion and postoperative alignment deviation. Methods Fifty-five osteoarthritis tibias with >10°varus preoperatively were divided into valgus, neutral, and varus groups based on their postoperative alignment deviation. A new method based on clinical practice was built using a 3D tibial model. Proximal and distal tibial torsions were measured by both the new and traditional methods. In addition, tibial osteotomy that followed the intramedullary osteotomy system was simulated on the 3D model in the varus and valgus groups to investigate the association between tibial torsion and alignment deviation. Results Proximal tibial torsion was smaller and distal torsion was greater in the valgus group than the other two groups, according to the new method (p = 0.03 and p = 0.02, respectively). No significant difference was found when comparing these torsions by the traditional method (p = 0.782 and p = 0.753, respectively). In the valgus group, the postoperative alignment deviation improved after simulated osteotomy guided by the intramedullary system, while no significant improvement was found in the varus group. Conclusion According to this new tibial-rotation evaluation method, valgus deviation in knee arthroplasty was identified as the main cause for knees in which the proximal tibial internal torsion is too small and the distal external torsion is too great. The use of an intramedullary system may help reduce this deviation. Trial registration Prospectively registered.

ACAP4, a GTPase-activating protein (GAP) for the ADP-ribosylation factor 6 (ARF6), plays import roles in cell migration, cell polarity, vesicle trafficking and tumorigenesis. Similarly, the ubiquitously expressed adaptor protein CrkII functions in a wide range of cellular activities, including cell proliferation, T cell adhesion and activation, tumorigenesis, and bacterial pathogenesis. Here, we demonstrate that ACAP4 physically interacts with CrkII. Biochemical experiments revealed that ACAP4550−660 and the SH3N domain of CrkII are responsible for the interaction. Functional characterization showed that the interaction is required for the recruitment of ACAP4 to the plasma membrane where ACAP4 functions to regulate the recycling of the signal transducer integrin β1. Thus, we suggest that the CrkII-ACAP4 complex may be involved in regulation of cell adhesion.

Visual and quantitative evaluation of the mitral valve is an important step in the clinicalworkflow according to experts as knowledge about mitral dynamics is crucial for interventionalplanning. We consider dynamic modeling of mitral valve annulus and leaflet coaptation by cubicB-splines, and the error of every tagging point is measured to the fitted curve to decide whether asecond round fitting is needed. After modeling, four clinically important points are identified. Thismodeling and identification are significantly important for further diagnosis and evaluation of thedynamic deformation of the mitral valve apparatus.

Multiple morphological abnormalities of flagella (MMAF) is one kind of severe teratozoospermia. Gene mutations reported in previous works only revealed the pathogenesis of approximately half of the MMAF cases, and more genetic defects in MMAF need to be explored. In the present study, we performed a genetic analysis on Han Chinese men with MMAF using whole-exome sequencing. After filtering out the cases with known gene mutations, we identified five novel mutation sites in the DNAH2 gene in three cases from three families. These mutations were validated through Sanger sequencing and absent in all control individuals. In silico analysis revealed that these DNAH2 variations are deleterious. The spermatozoa with DNAH2 mutations showed severely disarranged axonemal structures with mitochondrial sheath defection. The DNAH2 protein level was significantly decreased and inner dynein arms were absent in the spermatozoa of patients. ICSI treatment was performed for two MMAF patients with DNAH2 mutations and the associated couples successfully achieved pregnancy, indicating good nuclear quality of the sperm from the DNAH2 mutant patients. Together, these data suggest that the DNAH2 mutation can cause severe sperm flagella defects that damage sperm motility. These results provide a novel genetic pathogeny for the human MMAF phenotype.

Background: Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis.Materials and Methods: From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM. TEC machine.Results: After apheresis, the median CEPP was 20.71% (IQR: 9.99–36.69%) and median PLT reduction rate was 25.87% (IQR: 21.78–36.23%). Further analysis showed that no significant difference was observed between PLT count with 800–1,000 × 109/L and > 1,000 × 109/L. The PLT counts significantly decreased (P < 0.001) after plateletpheresis, the red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB), and hematocrit (HCT) levels showed no significant differences before- or after- plateletpheresis. Multivariate analysis showed that female sex (P = 0.009) and HGB (P = 0.010) before apheresis were associated with CEPP. Female (P = 0.022), HCT (P = 0.001) and blood volume (P = 0.015) were associated with the PLT reduction rate. Furthermore, symptoms were relieved after apheresis in patients whose PLT count was 800–1,000 × 109/L accompanied with symptoms.Conclusions: It is reasonable to perform plateletpheresis when the PLT count is over 800 × 109/L and patients are complicated by clinical symptoms such as dizziness, headache, somnolence, and stupor. Plateletpheresis is effective in removing PLTs especially in females with high HGB.

Respiratory diseases, especially the pandemic of respiratory infectious diseases and refractory chronic lung diseases, remain a key clinical issue and research hot spot due to their high prevalence rates and poor prognosis. In this review, we aimed to summarize the recent advances in the therapeutic effects and molecular mechanisms of key common bioactive compounds from Chinese herbal medicine. Based on the theories of traditional Chinese medicine related to lung diseases, we searched several electronic databases to determine the high-frequency Chinese medicines in clinical application. The active compounds and metabolites from the selected medicines were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) by analyzing oral bioavailability and drug similarity index. Then, the pharmacological effects and molecular mechanisms of the selected bioactive compounds in the viral and bacterial infections, inflammation, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, and lung cancer were summarized. We found that 31 bioactive compounds from the selected 10 common Chinese herbs, such as epigallocatechin-3-gallate (EGCG), kaempferol, isorhamnetin, quercetin, and β-sitosterol, can mainly regulate NF-κB, Nrf2/HO-1, NLRP3, TGF-β/Smad, MAPK, and PI3K/Akt/mTOR pathways to inhibit infection, inflammation, extracellular matrix deposition, and tumor growth in a series of lung-related diseases. This review provides novel perspectives on the preclinical study and clinical application of Chinese herbal medicines and their bioactive compounds against respiratory diseases.

Glutaminase 1 (GLS1) has recently been reported to be expressed in microglia and plays a crucial role in neuroinflamation. Significantly increased level of GLS1 mRNA expression together with neuroinflammation pathway were observed in postmortem prefrontal cortex from depressed patients. To find out the function of microglial GLS1 in depression and neuroinflammation, we generated transgenic mice (GLS1 cKO), postnatally losing GLS1 in microglia, to detect changes in the lipopolysaccharide (LPS)-induced depression model. LPS-induced anxiety/depression-like behavior was attenuated in GLS1 cKO mice, paralleled by a significant reduction in pro-inflammatory cytokines and an abnormal microglia morphological phenotype in the prefrontal cortex. Reduced neuroinflammation by GLS1 deficient microglia was a result of less reactive astrocytes, as GLS1 deficiency enhanced miR-666-3p and miR-7115-3p levels in extracellular vesicles released from microglia, thus suppressing astrocyte activation via inhibiting Serpina3n expression. Together, our data reveal a novel mechanism of GLS1 in neuroinflammation and targeting GLS1 in microglia may be a novel strategy to alleviate neuroinflammation-related depression and other disease.

Osteoarthritis (OA) is an age-related disease, which is mainly treated with oral, topical, and/or intra-articular options to relieve symptoms and lack of specific treatment measures. Fibroblasts (FLS) are crucial cells in joint inflammation and destruction. Cellular senescence plays an important role during OA pathogenesis and senescent cells exhibit cell-cycle arrest and senescence-associated secretory phenotype (SASP). SRY-related HMG-box 4 (SOX4) is a contributing factor during many developmental processes and is elevated in inflamed synovium than in noninflamed synovium from arthritis patients. This study was designed to investigate whether SOX4 participate in the pathogenesis of OA by affecting FLS senescence and explore the internal mechanism. Firstly, we found that FLS cells exhibited more cellular senescence in OA compared with control group. We also verified the role of reactive oxygen species (ROS)/TGF-β signal in the induction of OA-FLS senescence. During the exploration of SOX4 in cell senescence, the results indicated that SOX4 activation promotes cell senescence and SASP of OA-FLS. Apart from that, we also confirmed that SOX4, regulated by ROS/TGF-β signal, was critical transcription factor associated with OA-FLS senescence. Therefore, SOX4 is likely to be a novel therapeutic target and early diagnostic marker during OA pathogenesis.

AimsS-phase kinase-associated protein 2 (Skp2) oncoprotein is overexpressed in a variety of cancer tissues and promotes the malignant development of cancer. The expression levels of chromobox homolog 7 (CBX7) protein are varied among different types of cancer tissues, but its role in cervical cancer is not clear. We aimed to examine the expression and clinical significance of Skp2 and CBX7 proteins as well as their correlations in cervical cancer.MethodsImmunohistochemistry was used to detect the expression of Skp2 and CBX7 proteins in the cancerous tissues and adjacent tissues of 64 patients with cervical cancer. Relevant clinicopathological data of these patients were collected, compared and analysed for the correlations.ResultsThe expression of Skp2 protein in cervical cancer (87.5%) was higher than that in paracancerous tissues (14.1%), and the expression was positively correlated with clinical stage, malignant degree, lymphatic metastasis, vascular invasion and interstitial invasion. The expression of CBX7 protein in cervical cancer (48.4%) was lower than that in paracancerous tissues (96.8%), and the expression was negatively correlated with clinical stage, malignant degree, interstitial invasion, vascular invasion and lymphatic metastasis. The expression of Skp2 protein and CBX7 protein in cervical cancer tissues and adjacent tissues was negatively correlated. The expression of Skp2 and CBX7 proteins was closely related to the clinicopathological features of cervical cancer.ConclusionsCBX7 may play the role of a tumour suppressor gene in cervical cancer and provide reference value for the diagnosis and new targeted treatment of cervical cancer.

We aimed to investigate the function and its possible mechanisms of long noncoding RNA (lncRNA) in acute myocardial infarction (AMI) model. Patients with AMI and normal volunteers were selected from our hospital. Sprague-Dawley rats were induced into in vivo model of AMI. H9c2 cells were treated with H2 O2 to generate injury model. A significantly lower serum gene expression of lncRNA CASC2 was detected. In rat models of AMI, lncRNA CASC2 gene expressions in heart tissue of mice with AMI were decreased. In in vitro model, downregulation of lncRNA CASC2 increased reactive oxygen species (ROS)-induced oxidative stress; lncRNA CASC2 induced NADPH oxidase (NOX-2) expression and suppressed miR-18a expression; MiR-18a promoted ROS-induced oxidative stress; downregulation of miR-18a decreased ROS-induced oxidative stress. The inhibition of miR-18a reversed the effects of CASC2 downregulation on ROS-induced oxidative stress in in vitro model of AMI. The activation of miR-18a reversed the effects of CASC2 on ROS-induced oxidative stress in in vitro model of AMI. These data for the first time suggest that lncRNA CASC2 have better protective effects on AMI, which could reduce oxidative stress through their carried miR-18a and subsequently downregulating the SIRT2/ROS pathway.

Qing Zhang,1,2 Hong Ji,1,2 Jian Shi,1,2 Longmei Wang,1,2 Lu Ding,1,2 Yufei Jiang,1,2 Xianjing Huang,1,2 Pingping Qiu Snr,1,2 Ping Li1,2 1Department of Reproductive Medicine, Women and Children’s Hospital Affiliated to Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Xiamen Key Laboratory of Reproduction and Genetics, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Pingping Qiu; Ping LiDepartment of Reproductive Medicine, Women and Children’s Hospital Affiliated to Xiamen University, Zhenhai Road 10, Xiamen, Fujian, 361003, People’s Republic of ChinaTel +86-592-2663987Fax +86-592-2662032Email Pingingqiu826@163.com; saarc2001@sina.comPurpose: The ratio of mitochondrial DNA to genomic DNA (mtDNA/gDNA) in embryo culture medium as a predictor of embryonic development is a new method of noninvasive embryo screening. However, current tests based on this concept have proven inconsistent. The aim of this study was to define the predictive value of the ratio of mtDNA/gDNA for embryonic developmental potential.Materials and Methods: We used digital PCR to measure mtDNA/gDNA ratios in day 3 culture media of 223 embryos from 56 patients. We compared the relationship between the predictive value of mtDNA/gDNA ratio and each of embryo fragmentation, embryo morphological grade, and blastocyst formation.Results: mtDNA/gDNA ratio decreased significantly with a decrease in embryo rating: 22.54 (44.66); 31.25 (36.97) and 46.33 (57.11); Grades A vs C, P = 0.006; B vs C, P = 0.015. mtDNA/gDNA ratio increased overall with an increase in embryo fragment content but did not differ significantly between high-, -medium, and poor-quality embryos. Interestingly, this trend differed from that of the unformed blastocysts. mtDNA/gDNA ratio of cleavage stage embryos forming blastocysts was lower (P=0.005). Trends of mtDNA/gDNA ratio differed according to inner cell mass (ICM) and trophectoderm (TE) levels, but not significantly. mtDNA/gDNA ratio in day 3 culture medium was not significantly improved over morphological scores.Conclusion: We hereby show the correlation of mtDNA/gDNA ratio in the culture medium of developing embryos. The correlation between the mtDNA/gDNA ratio and early embryonic development was controversial. Furthermore, an increase in mtDNA/gDNA ratio might indicate reduced development potential, but the difference remains insufficient for application as a clinical predictor.Keywords: mtDNA/gDNA, embryo, digital PCR, blastocyst

Background The occurrence of neural tube defects is a complex process in which genes, internal and external environment and other factors jointly influence and occur interactively. In this experiment, animal models of different energy balance states are constructed. To explore the mechanism of fos and leptin-leptin receptor during neural tube development of offspring under different energy states and its effect on neural tube development of offspringMethods Using gene identification technology to obtain Mex3c+/- negative energy balance mice and high-fat diet to obtain positive energy balance mice, and obtain E10.5d, E12.5d, E14.5d embryos. We will verify the expression of fos, leptin, LEPR, nestin, PAX3, and H3K27me3 proteins in the neural tube of the offspring through relevant experimental methods.Results We have successfully constructed animal models, Control group (18.82g±1.54g), Mex3c group (18.84g±1.08g), HFD group (22.61g±1.10g). Neural tube HE staining showen that compared with the Control group, the neuronal maturity of the Mex3c group and the HFD group was reduced. Immunohistochemical staining showed that both fos and leptin were expressed on the nucleus, and LEPR was expressed on the cell membrane. Western blot experiments showed that compared with the Control group, the Mex3c group and the HFD group had low expression of fos protein (P＜0.01), the Mex3c group had high expression of LEPR protein (P＜0.01) and the HFD group had high expression of LEPR protein (P＜0.01). Immunostaining experiments showed that nestin was expressed in nerve fibers, and PAX3 and H3K27me3 were both expressed in the nucleus. Western blooting experiment showed that compared with the Control group, the Mex3c group had high expression of nestin protein (P＜0.01), PAX3 protein (P＜0.01), H3K27me3 (P＜0.01), and the HFD group had high expression of nestin protein (P＜0.01). ) And PAX3 protein (PPConclusionsMex3c regulates leptin and LEPR by enhancing the expression of fos mRNA to participate in the neural tube development process of offspring. The neural tube nestin, PAX3, and H3K27me3 of the offspring of Mex3c+/- mice and high-fat diet mice continue to be highly expressed. Mex3c+/- mice express low leptin, and high-fat diet mice highly express leptin; preliminary reveals the regulation of different energy states Leptin-LEPR is involved in the process of neurodevelopment. Mex3c mutant mice and mice on a high-fat diet lead to decreased neurodevelopmental maturity.

Spinal cord injury (SCI) is one of the most challenging clinical issues. It is characterized by the disruption of neural circuitry and connectivity, resulting in neurological disability. Adipose-derived stem cells (ADSCs) serve as a promising source of therapeutic cells for SCI treatment. However, the therapeutic outcomes of direct ADSCs transplantation are limited in the presence of an inflammatory microenvironment. Herein, a cell-adaptable neurogenic (CaNeu) hydrogel was developed as a delivery vehicle for ADSCs to promote neuronal regeneration after SCI. The dynamic network of CaNeu hydrogel loaded with ADSCs provides a cell-infiltratable matrix that enhances axonal growth and eventually leads to improved motor evoked potential, hindlimb strength, and coordination of complete spinal cord transection in rats. Furthermore, the CaNeu hydrogel also establishes an anti-inflammatory microenvironment by inducing a shift in the polarization of the recruited macrophages toward the pro-regeneration (M2) phenotype. Our study showed that the CaNeu-hydrogel‒mediated ADSCs delivery resulted in significantly suppressed neuroinflammation and apoptosis, and that this phenomenon involved the PI3K/Akt signaling pathway. Our findings indicate that the CaNeu hydrogel is a valuable delivery vehicle to assist stem cell therapy for SCI, providing a promising strategy for central nervous system diseases.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.