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Abstract Melatonin (N‐acetyl‐5‐methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive‐like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX‐operated mice is sufficient to ameliorate depressive‐like behaviors. Conversely, microbiota transplantation from OVX‐operated mice or melatonin‐treated OVX‐operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX‐operated mice, confers the recipient with depressive‐like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive‐like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX‐induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

Understanding the complex influencing factors of soil erosion is critical for maintaining regional ecological security. The revised wind erosion equation (RWEQ) and partial least squares regression (PLSR) model were used to reveal the primary factors affecting soil erosion. Based on the results of the RWEQ model, the wind erosion area was 8,439.3 km2 in 2018, accounting for 54.3% of the total planning area, and mild erosion, moderate erosion, intense erosion, very intense erosion, and fierce erosion accounted for 18.22%, 11.43%, 11.78%, 10.16%, and 2.74% of the total planning area, respectively. Based on the results of the PLSR model, the results indicate that the proportion of mining land, meteorological indicators, and mean square deviation of slope difference were positively correlated with the soil erosion area, intensity, and severity, respectively. The proportion of grassland and forest land was negatively correlated with the soil erosion area, intensity, and severity. The mean square deviation of slope difference, the mean square deviation of difference in elevation, and the proportion of urban land use contributed the most to the soil erosion severity index, with variable importance in projection (VIP) scores of 1.55, 1.44 and 1.43, respectively. The mean square deviation of slope difference, the proportion of urban land, and the mean square deviation of difference in elevation contributed the most to the soil erosion area, with VIP scores of 1.53, 1.26 and 1.24, respectively. The results provide new insights into wind erosion and the influences of weather conditions and human influences, which can guide regional soil and water conservation planning in wind erosion regions.

Objective To evaluate the efficacy of double U-stitch and modified “double U-stitch pancreaticojejunostomy” in pancreaticoduodenectomy. Methods We retrospectively analyzed the clinical information of 150 patients who underwent pancreaticoduodenectomy between January 2022 and September 2023 in Wang Wei’s team in department of pancreatic surgery, Fudan University Shanghai Cancer Center. The patients were divided into two groups according to the pancreaticojejunostomy method: the double U-stitch 1.0 group (70 cases before modification) and the double U-stitch 2.0 group (80 cases after modification). The postoperative complications of the two groups were compared. Results The overall postoperative complications were significantly lower in the double U-stitch 2.0 group as compared with the double U-stitch 1.0 group (13.8% vs. 38.6%, P=0.001). The incidence of clinically relevant pancreatic fistula was 18.6% in the double U-stitch 1.0 group, while this was significantly decreased in the double U-stitch 2.0 group (6.3%) (P=0.021). Postoperative extraluminal hemorrhage occurred in 5 patients in the double U-stitch 1.0 group, while in the double U-stitch 2.0 group, only one patient experienced postoperative intraluminal hemorrhage, the difference was statistically significant between two groups (P=0.007). The median postoperative length of hospital stay was significantly shorter in the double U-stitch 2.0 group than that in the double U-stitch 1.0 group (11 d vs. 14 d, P=0.001). Conclusions The modified “double U-stitch pancreaticojejunostomy” can significantly reduce the incidence of clinically relevant pancreatic fistula and other relevant severe complications, which helps improve the safety of the procedure.

Abstract Objective We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30–32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). Methods We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25–28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30–32 °C) with distal aortic perfusion (s-TAR group). Results The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. Conclusions s-TAR under mild hypothermia (30–32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

Objective: The clinical impact of baseline mitral regurgitation (MR) on the outcomes after transcatheter aortic valve replacement (TAVR) is not clear. This study sought to assess the clinical impact of baseline MR on outcomes after TAVR. Methods: The study was a retrospective analysis. Data was from 120 consecutive patients with severe aortic stenosis (AS) undergoing TAVR at our center from June 2018 and July 2020. Clinical outcomes were assessed at 30-day, 1- and 2-year follow-up. Results: The median follow-up was 736.0 (interquartile range, 666.0–965.0) days. Overall survival in patients with nonsignificant and significant baseline MR was not significantly different, while patients from the improved MR group after TAVR demonstrated a significantly higher survival than unchanged or worsened MR group during 2-year follow-up. NYHA functional class had generally improved at 1 year, with only 8.3 % of patients with nonsignificant MR and 17.5 % of patients with significant MR in class III or IV. Patients with improved MR at 1 year after TAVR had a significantly higher LVEF, smaller LVEDD and LVESD than those with unchanged or worsened MR. Among the significant baseline MR group, 70.4 % and 80.0 % of patients had improved to nonsignificant MR at 30-day and 1-year follow-up after TAVR, respectively. Conclusions: Significant baseline MR was not associated with the increased risk of all-cause mortality 2 years after TAVR. Significant baseline MR was improved in most patients at 1 year after TAVR. Patients with unchanged or worsened MR had an increased all-cause mortality.

Abstract Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB−/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Abstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. Methods We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. Results In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. Conclusion P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract

Abstract Background Evidence about safety and efficacy of transcatheter aortic valve replacement (TAVR) with the Venus A-Valve system (Venus Medtech, Hangzhou, China) remains limited for patients with pure native aortic regurgitation (PNAR). Objectives The single-center study sought to report the one-year clinical outcomes of the Venus A-Valve in the treatment of PNAR. Methods This study was a retrospective analysis of prospectively collected data. Data was from all consecutive patients who had PNAR and underwent TAVR with the Venus A-Valve system at our center from July 2020 and June 2021. Procedural and clinical outcomes up to one year were analyzed using Valve Academic Research Consortium-2 criteria. Results A total of 45 consecutive patients with PNAR underwent transfemoral TAVR with the Venus A-Valve system. The Mean age was 73.5 ± 5.5 years and 26.7% were female. All the TAVR procedures were performed via transfemoral access. Implantations were successful in 44 cases (97.8%). Only one patient was converted to surgical aortic valve replacement. No patient died intraoperatively. No second valve was implanted. In-hospital mortality rate was 2.3%. The one-year all-cause mortality rate was 4.7% without cardiovascular related death. No patient had moderate or severe paravalvular leakage during follow-up. At one year, the mean pressure gradient was 8.8 ± 0.9 mmHg, and left ventricular ejection fraction increased to 61.5 ± 3.6%. Conclusions This single-center study demonstrated the safety and efficacy of transfemoral TAVR with the Venus A-Valve in the treatment of patients with PNAR.

Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.