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Abstract In this study, the hepatoprotective effect of alkali extract (NE) of water bamboo shoot (WBS) against acute alcoholic liver injury (ALI) in mice was evaluated, and its underlying mechanisms were explored. Animal experiment demonstrated that NE exhibited hepatoprotective effect on alcoholic intake‐induced ALI via significantly enhancing the hepatic activities of alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT), whereas significantly attenuated hepatic levels of malondialdehyde (MDA), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α). The potential molecular mechanism and bioactive compounds of NE against ALI were explored by bioinformatics analysis and isosinensetin was found to be the major bioactive compounds in NE against ALI. The western blot analysis showed that NE inhibited phosphorylation of p65 and IκBα to suppress the NF‐κB pathway. Overall our result indicated that WBS possesses potential hepatoprotective effects against ALI.

Abstract The present study investigated the effect of type III Neuregulin-1 (NRG-1) on changes in the myelin sheath and the recovery of nerve function during the regeneration process following autologous nerve transplantation. Seventy-two Sprague–Dawley rats were divided into a Blank, Model and (antisense oligonucleotide, ASON) group. The Model and ASON groups of SD rats were subjected to autologous nerve transplantation, and the Blank group only had the sciatic nerve exposed. The Model and ASON groups were given local injections of 2 ml PBS buffer solution and 2 ml ASON of Type III NRG-1, respectively, the NRG-1 type III was inhibited by ASON. Changes in the sciatic nerve functional index (SFI) and conduction velocities were observed at different 6 time points. Regeneration of the myelin sheath was observed using transmission electron microscopy. Type III NRG-1 protein was detected using Western blotting and immunohistochemistry, and NRG-1 mRNA was detected using PCR. The SFI of the ASON group was lower than the Model group after transplantation. The conduction velocities of the ASON group on the 14th and 21st days after autologous nerve transplantation were lower than the Model group (P

Abstract Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.

AIM: To analyze the effect of full-femtosecond small incision lenticule extraction(SMILE)on the treatment of high myopia based on propensity score matching.METHODS: A total of 48 cases(48 eyes)of high myopia patients who underwent SMILE surgery in our hospital from May 2019 to May 2021 were selected as the observation group, and 48 cases(48 eyes)of high myopia patients who underwent FS-LASIK surgery were matched using propensity score matching as the control group. Follow up for 6mo after surgery, the changes in cylindrical, central corneal thickness, uncorrected visual acuity(UCVA), corneal endothelial cell related indicators [percentage of hexagonal endothelial cells(6A), coefficient of variation(CV)of endothelial cell area, central corneal endothelial cell density(ECD)] and corneal biomechanical indicators [simulated Goldman intraocular pressure(IOPg), corneal hysteresis(CH), corneal resistance factor(CRF), corneal compensated intraocular pressure(IOPcc)] between the two groups were compared, and the incidence of complications in both groups of patients was recorded.RESULTS: Both groups of patients showed significant improvements in cylindrical and UCVA at 3 and 6mo after surgery, as well as decreased central corneal thickness, corneal endothelial cells, and corneal biomechanics related indicators. The changes in the observation group were more significant(all P0.05).CONCLUSION: SMILE has a definite effect on patients with high myopia and is helpful to improve visual acuity.

[Objective] Ecological land fragmentation has a serious impact on the structural integrity and function of the ecosystem. The conflict between construction land expansion and ecological land fragmentation is one of the problems that need to be solved in the process of implementing the development and protection strategy for harmonious coexistence between humans and nature. [Methods] In this study, based on the analysis of temporal and spatial changes in ecological land, a comprehensive indicator system of fragmentation degree was established for the southern Jiangsu Province region to explore the temporal and spatial characteristics of ecological land fragmentation degree. Based on the theory of the environmental Kuznets curve (EKC), the response of ecological land fragmentation degree to construction land expansion was investigated. [Results] (1) From 2000 to 2020, the ecological land in southern Jiangsu Province was mainly converted into construction land, followed by cultivated land. A certain amount of cultivated land and a small amount of construction land were converted into ecological land; (2) The degree of ecological land fragmentation increased first and then decreased. Along the Yangtze River and in the surrounding areas of key water bodies such as the Taihu Lake, the Gucheng Lake, and the Gehu Lake, there was a remarkable increase in the degree of fragmentation; (3) There is an inverted U-shaped relationship between the scale of construction land and the fragmentation of ecological land. With the increase of the area of construction land, the degree of fragmentation of ecological land increases first and then decreases. [Conclusion] The spatiotemporal response of ecological land fragmentation to construction land expansion is consistent with the EKC theory, and most urban centers in southern Jiangsu Province have reached the inflection point by 2020. By exploring the balance between ecological land occupation and compensation, conducting ecological planning in advance, building ecological barriers, timely assessing the impact of construction land expansion on ecological land, and formulating response measures, the layout coordination of construction land and ecological land will be improved, and the coordinated progress of “smart growth” and green development can be realized.

Abstract A representative class of kagome materials, AV3Sb5 (A = K, Rb, Cs), hosts several unconventional phases such as superconductivity, $${{\mathbb{Z}}}_{2}$$ Z 2 non-trivial topological states, and electronic nematic states. These can often coexist with intertwined charge-density wave states. Recently, the discovery of the isostructural titanium-based single-crystals, ATi3Bi5 (A = K, Rb, Cs), which exhibit similar multiple exotic states but without the concomitant charge-density wave, has opened an opportunity to disentangle these complex states in kagome lattices. Here, we combine high-resolution angle-resolved photoemission spectroscopy and first-principles calculations to investigate the low-lying electronic structure of RbTi3Bi5. We demonstrate the coexistence of flat bands and several non-trivial states, including type-II Dirac nodal lines and $${{\mathbb{Z}}}_{2}$$ Z 2 non-trivial topological surface states. Our findings also provide evidence for rotational symmetry breaking in RbTi3Bi5, suggesting a directionality to the electronic structure and the possible emergence of pure electronic nematicity in this family of kagome compounds.

Abstract Ethnopharmacological relevance Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. Aim of the study Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. Materials and methods The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. Results The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ’s protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). Conclusions Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.

Abstract Background Epstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV. Methods Six tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis. Results 16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine. Conclusion Collectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.

Abstract Background Bladder cancer (BLCA) represents a highly heterogeneous disease characterized by distinct histological, molecular, and clinical features, whose tumorigenesis and progression require aberrant metabolic reprogramming of tumor cells. However, current studies have not expounded systematically and comprehensively on the metabolic heterogeneity of BLCA. Methods The UCSC XENA portal was searched to obtain the expression profiles and clinical annotations of BLCA patients in the TCGA cohort. A total of 1,640 metabolic-related genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Then, consensus clustering was performed to divide the BLCA patients into two metabolic subtypes according to the expression of metabolic-related genes. Kaplan-Meier analysis was used to measure the prognostic values of the metabolic subtypes. Subsequently, comparing the immune-related characteristics between the two metabolic subtypes to describe the immunological difference. Then, the Scissor algorithm was applied to link the metabolic phenotypes and single-cell transcriptome datasets to determine the biomarkers associated with metabolic subtypes and prognosis. Finally, the clinical cohort included 63 BLCA and 16 para-cancerous samples was used to validate the prognostic value and immunological correlation of the biomarker. Results BLCA patients were classified into two heterogeneous metabolic-related subtypes (MRSs) with distinct features: MRS1, the subtype with no active metabolic characteristics but an immune infiltration microenvironment; and MRS2, the lipogenic subtype with upregulated lipid metabolism. These two subtypes had distinct prognoses, molecular subtypes distributions, and activations of therapy-related pathways. MRS1 BLCAs preferred to be immuno-suppressive and up-regulated immune checkpoints expression, suggesting the well-therapeutic response of MRS1 patients to immunotherapy. Based on the Scissor algorithm, we found that S100A7 both specifically up-regulated in the MRS1 phenotype and MRS1-tumor cells, and positively correlated with immunological characteristics. In addition, in the clinical cohort included 63 BLCA and 16 para-cancerous samples, S100A7 was obviously associated with poor prognosis and enhanced PD-L1 expression. Conclusions The metabolic subtype with S100A7 high expression recognizes the immuno-suppressive tumor microenvironment and predicts well therapeutic response of immunotherapy in BLCA. The study provides new insights into the prognostic and therapeutic value of metabolic heterogeneity in BLCA.

Abstract Stable picosecond dissipative soliton pulses were observed in an ytterbium-doped fiber laser employing a high-quality mixture of BP/SnSe2-PVA saturable absorber (SA). The modulation depth, saturation intensity, and non-saturable loss of the mixture of BP/SnSe2-PVA SA were measured with values of 5.98%, 18.37 MW/cm2, and 33%, respectively. Within the pump power range of 150–270 mW, stable dissipative soliton pulses were obtained with an output power of 1.68–4 mW. When the minimum pulse duration is 1.28 ps, a repetition rate of 0.903 MHz, center wavelength of 1064.38 nm and 3 dB bandwidth of 2 nm were obtained. The maximum pulse energy of 4.43 nJ and the signal-to-noise ratio up to 72 dB were achieved at pump power of 270 mW. The results suggest that the BP/SnSe2-PVA mixture SA has outstanding nonlinear saturable absorption characteristics and broad ultrafast laser applications. Graphical Abstract

Abstract Background The aim of this study was to perform a retrospective analysis of patients with acute anterior wall ST-segment elevation myocardial infarction (AAW-STEMI) whose left anterior descending (LAD) artery was completely occluded and reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influencing factors and prognostic value of left ventricular systolic dysfunction (LVSD) in the acute phase of acute myocardial infarction (AMI). Methods A total of 304 patients with AAW-STEMI were selected. The selected patients were divided into two groups: the preserved left ventricular ejection fraction (pLVEF) group (LVEF ≥ 50%, n = 185) and the reduced left ventricular ejection fraction (rLVEF) group (LVEF

Abstract Acute lung injury (ALI) is an adverse disease of the respiratory system, and one of its prevalent causes is sepsis induction. Cell pyroptosis facilitates the progression of ALI and lncRNAs play critical roles in ALI. Thus, this research seeks to investigate the specific mechanism of NEAT1 in sepsis‐ALI.BEAS‐2B cells were exposed to lipopolysaccharide (LPS) to construct a cell model of sepsis‐induced ALI. The gene and protein expression were assessed using qRT‐PCR and western blot. Cell viability was identified by CCK‐8. Cell death was discovered using PI staining. The secretion of IL‐1β and IL‐18 was examined using ELISA. The interconnections among NEAT1, miR‐26a‐5p, and ROCK1 were confirmed using starbase, luciferase assay, and RIP.LPS treatment augmented NEAT1 and ROCK1 levels while mitigating miR‐26a‐5p level in BEAS‐2B cells. Additionally, LPS treatment facilitated cell death and cell pyroptosis, whereas NEAT1 silencing could reverse these effects in BEAS‐2B cells. Mechanistically, NEAT1 positively mediated ROCK1 expression by targeting miR‐26a‐5p. Furthermore, miR‐26a‐5p inhibitor offset NEAT1 depletion‐mediated suppressive effects on cell death and cell pyroptosis. ROCK1 upregulation decreased the inhibitory impacts produced by miR‐26a‐5p overexpression on cell death and cell pyroptosis. Our outcomes demonstrated NEAT1 could reinforce LPS‐induced cell death and cell pyroptosis by repressing the miR‐26a‐5p/ROCK1 axis, thereby worsening ALI caused by sepsis. Our data indicated NEAT1, miR‐26a‐5p, and ROCK1 might be biomarkers and target genes for relieving sepsis‐induced ALI.

Objective: Osteoarthritis (OA), widely seen in the elderly, is featured by cartilage degradation, subchondral bone remolding, and synovium inflammation. Currently, there is no cure for OA development. Phillygenin (PHI), an active ingredient from the Forsythiae Fructus, possesses many biological properties, such as anti-inflammation and anti-oxidative stress in several diseases. However, the potential effects and underlying mechanisms of PHI on OA remain unclear. Methods: Western blotting, RT-PCR, ELISA and tissue staining were employed to explore the mechanisms by which PHI exerted a protective effect on IL-1β-induced production of pro-inflammation cytokines and extracellular matrix (ECM) degradation in primary murine chondrocytes and destabilization of the medial meniscus (DMM) mouse models. Results: In this study, we found that PHI inhibited the production of pro-inflammation cytokines and ECM degradation induced by IL-1β in primary murine chondrocytes. Mechanically, PHI inhibited the NF-κB pathway via activating nuclear factor (erythrluteolind-derived 2)-like 2 (Nrf2). In vivo experiments also confirmed the chondroprotection of PHI in DMM mouse models. Conclusion: PHI alleviated IL-1β-induced inflammation cytokines and ECM degradation via activating Nrf2 and inhibiting NF-κB pathway. The translational potential of this article: This study provides a biological rationale for the use of PHI as a potential candidate for OA treatment.

Tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3 or TIPE3) functions as a transfer protein for lipid second messengers. TIPE3 is highly upregulated in several human cancers and has been established to significantly promote tumor cell proliferation, migration, and invasion and inhibit the apoptosis of cancer cells. Thus, inhibiting the function of TIPE3 is expected to be an effective strategy against cancer. The advancement of artificial intelligence (AI)-driven drug development has recently invigorated research in anti-cancer drug development. In this work, we incorporated DFCNN, Autodock Vina docking, DeepBindBC, MD, and metadynamics to efficiently identify inhibitors of TIPE3 from a ZINC compound dataset. Six potential candidates were selected for further experimental study to validate their anti-tumor activity. Among these, three small-molecule compounds (K784-8160, E745-0011, and 7238-1516) showed significant anti-tumor activity in vitro, leading to reduced tumor cell viability, proliferation, and migration and enhanced apoptotic tumor cell death. Notably, E745-0011 and 7238-1516 exhibited selective cytotoxicity toward tumor cells with high TIPE3 expression while having little or no effect on normal human cells or tumor cells with low TIPE3 expression. A molecular docking analysis further supported their interactions with TIPE3, highlighting hydrophobic interactions and their shared interaction residues and offering insights for designing more effective inhibitors. Taken together, this work demonstrates the feasibility of incorporating deep learning and MD simulations in virtual drug screening and provides inhibitors with significant potential for anti-cancer drug development against TIPE3−.

Abstract As a member of Xenes family, germanene has excellent nonlinear saturable absorption characteristics. In this work, we prepared germanene nanosheets by liquid phase exfoliation and measured their saturation intensity as 0.6 GW/cm2 with a modulation depth of 8%. Then, conventional solitons with a pulse width of 946 fs and high-energy noise-like pulses with a pulse width of 784 fs were obtained by using germanene nanosheet as a saturable absorber for a mode-locked Erbium-doped fiber laser. The characteristics of the two types of pulses were investigated experimentally. The results reveal that germanene has great potential for modulation devices in ultrafast lasers and can be used as a material for creation of excellent nonlinear optical devices to explore richer applications in ultrafast photonics. Graphical Abstract

Abstract Studying the real-time face expression state of teachers in class was important to build an objective classroom teaching evaluation system based on AI. However, the face-to-face communication in classroom conditions was a real-time process that operated on a millisecond time scale. Therefore, in order to quickly and accurately predict teachers’ facial expressions in real time, this paper proposed an improved YOLOv5 network, which introduced the attention mechanisms into the Backbone model of YOLOv5. In experiments, we investigated the effects of different attention mechanisms on YOLOv5 by adding different attention mechanisms after each CBS module in the CSP1_X structure of the Backbone part, respectively. At the same time, the attention mechanisms were incorporated at different locations of the Focus, CBS, and SPP modules of YOLOv5, respectively, to study the effects of the attention mechanism on different modules. The results showed that the network in which the coordinate attentions were incorporated after each CBS module in the CSP1_X structure obtained the detection time of 25 ms and the accuracy of 77.1% which increased by 3.5% compared with YOLOv5. It outperformed other networks, including Faster-RCNN, R-FCN, ResNext-101, DETR, Swin-Transformer, YOLOv3, and YOLOX. Finally, the real-time teachers’ facial expression recognition system was designed to detect and analyze the teachers’ facial expression distribution with time through camera and the teaching video.

Abstract The recently discovered kagome metals AV3Sb5 (A = Cs, Rb, K) exhibit a variety of intriguing phenomena, such as a charge density wave (CDW) with time-reversal symmetry breaking and possible unconventional superconductivity. Here, we report a rare non-monotonic evolution of the CDW temperature (T CDW) with the reduction of flake thickness approaching the atomic limit, and the superconducting transition temperature (T c) features an inverse variation with T CDW. T CDW initially decreases to a minimum value of 72 K at 27 layers and then increases abruptly, reaching a record-high value of 120 K at 5 layers. Raman scattering measurements reveal a weakened electron-phonon coupling with the reduction of sample thickness, suggesting that a crossover from electron-phonon coupling to dominantly electronic interactions could account for the non-monotonic thickness dependence of T CDW. Our work demonstrates the novel effects of dimension reduction and carrier doping on quantum states in thin flakes and provides crucial insights into the complex mechanism of the CDW order in the family of AV3Sb5 kagome metals.

Abstract Background Pregnant and puerperal women are high-risk populations for developing venous thromboembolism (VTE). Plasma D-dimer (D-D) is of good value in the diagnosis of exclusion of VTE in the nonpregnant population. Since there is no consensus reference range of plasma D-D applicable to pregnant and puerperal women, the application of plasma D-D is limited. To investigate the change characteristics and the reference range of plasma D-D levels during pregnancy and puerperium and to explore the pregnancy- and childbirth-related factors affecting plasma D-D levels and the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. Methods A prospective cohort study was conducted with 514 pregnant and puerperal women (cohort 1), and 29 puerperal women developed VTE 24–48 h after caesarean section (cohort 2). In cohort 1, the effects of the pregnancy- and childbirth-related factors on the plasma D-D levels were analyzed by comparing the differences in plasma D-D levels between different groups and between different subgroups. The 95th percentiles were calculated to establish the unilateral upper limits of the plasma D-D levels. The plasma D-D levels at 24–48 h postpartum were compared between normal singleton pregnant and puerperal women in cohort 2 and women from the cesarean section subgroup in cohort 1, binary logistic analysis was used to analyze the relevance between plasma D-D level and the risk of VTE developing 24–48 h after caesarean section, and a receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. Results The 95% reference ranges of plasma D-D levels in the normal singleton pregnancy group were ≤ 1.01 mg/L in the first trimester, ≤ 3.17 mg/L in the second trimester, ≤ 5.35 mg/L in the third trimester, ≤ 5.47 mg/L at 24–48 h postpartum, and ≤ 0.66 mg/L at 42 days postpartum. The plasma D-D levels of the normal twin pregnancy group were significantly higher than those of the normal singleton pregnancy group during pregnancy (P

Abstract Background Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown. Method We used the Rarα knockout mouse model and the wild-type ovariectomized mouse models with subcutaneous injection of RA (2.5 mg/kg) or E2 (0.1 µg/kg) to study the role and mechanism of RA-RAR signaling on the vaginal opening. The effects of Rarα deletion on Ctnnb1 mRNA levels and cell apoptosis in the vaginas were analyzed by real-time PCR and immunofluorescence, respectively. The effects of RA on the expression of β-catenin and apoptosis in the vaginas were analyzed by real-time PCR and western blotting. The effects of E2 on RA signaling molecules were analyzed by real-time PCR and western blotting. Results RA signaling molecules were expressed in vaginal epithelial cells, and the mRNA and/or protein levels of RALDH2, RALDH3, RARα and RARγ reached a peak at the time of vaginal opening. The deletion of Rarα resulted in 25.0% of females infertility due to vaginal closure, in which the mRNA (Ctnnb1, Bak and Bax) and protein (Cleaved Caspase-3) levels were significantly decreased, and Bcl2 mRNA levels were significantly increased in the vaginas. The percentage of vaginal epithelium with TUNEL- and Cleaved Caspase-3-positive signals were also significantly decreased in Rarα −/− females with vaginal closure. Furthermore, RA supplementation of ovariectomized wild-type (WT) females significantly increased the expression of β-catenin, active β-catenin, BAK and BAX, and significantly decreased BCL2 expression in the vaginas. Thus, the deletion of Rarα prevents vaginal opening by reducing the vaginal β-catenin expression and epithelial cell apoptosis. The deletion of Rarα also resulted in significant decreases in serum estradiol (E2) and vagina Raldh2/3 mRNA levels. E2 supplementation of ovariectomized WT females significantly increased the expression of RA signaling molecules in the vaginas, suggesting that the up-regulation of RA signaling molecules in the vaginas is dependent on E2 stimulation. Conclusion Taken together, we propose that RA-RAR signaling in the vaginas promotes vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis.

Purpose: Chinese Martial arts is becoming increasingly prevalent worldwide. There is insufficient evidence to prove the health effects of martial arts due to methodological weaknesses. The aim of this study was to better understand the effects of Chinese martial arts on the skeletal and muscular status of the lumbar spine by quantitative magnetic resonance imaging (MRI). Methods: Nine elite martial arts athletes, eighteen amateurs, and eighteen sedentary volunteers underwent T2 mapping and q-Dixon imaging of the lumbar spine on a 3T (Tesla) system. T2 (Transverse) relaxation times were measured in different regions of interest of the intervertebral disc (IVD). Fat Fraction (FF) was measured in the paraspinal muscles and vertebral body. Results: Compared to the sedentary controls, martial arts athletes showed: (1) increased T2 times in the nucleus pulposus, especially in the central nucleus pulposus (P = 0.004); (2) decreased FF in the multifidus and erector spinae (all P

ABSTRACTCancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A*0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8+T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A*0201+, CT23+), but no killing effect on tumor cells (HLA-A*0201−, CT23+). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.

Solar-driven interfacial evaporation has emerged as an efficient and sustainable way to generate freshwater from seawater to address the crisis of drinkable water. Though rational designs of photothermal materials and structures are essential to the interfacial solar evaporation process, the salt accumulation remains a challenge to the long-term operation of seawater desalination. Here, we report a high-yield and low-cost natural sphagnum as solar steam generator with ultra-fast water transportation, unique microstructure to prevent salting out, and high evaporation rates. The carbonized sphagnum based photothermal evaporator exhibits a strong broad-band light absorption (>97.0 %). During the solar steam generation, a high evaporation rate of 3.53 kg m−2 h−1 was achieved under 1.0 sun illumination. More significantly, the 3D sphagnum evaporator shows excellent selective filtration of salt ions and cycling stability in actual sea water even high salinity solution (10 wt.% NaCl) for 7 days. This work provides an environmentally friendly and cost-effective photothermal material for large-scale seawater desalination, and treatment of waste water with high ions concentration.

Our previous research demonstrated that the glucomannan WSRP-1b, which was obtained from waste biomass of Rosa Setate x Rosa Rugosa, had potent immunostimulatory activity. However, the specific mechanisms involved in the activation of RAW264.7 macrophages by WSRP-1b remain unclear. Scanning electron microscopy, atomic force microscopy and Congo red analyses revealed that WSRP-1b exhibited a flake structure with irregular curls and had a triple-helix conformation in solution. The immunostimulation assays showed that WSRP-1b could substantially enhance macrophages phagocytosis and promote the accumulation of iNOS, TNF-α, and IL-6 mRNA. Western blot analysis indicated that the expression of mitogen-activated protein kinases (MAPKs) was upregulated in WSRP-1b-induced RAW264.7 cells. Furthermore, pretreatment of RAW 264.7 cells using specific inhibitors against MAPKs and NF-κB remarkably attenuated nitric oxide production and cytokine secretion. These data suggest that WSRP-1b activates RAW264.7 macrophages via the MAPK and NF-κB signaling pathways and may be a novel immunomodulatory agent for hypoimmunity disease therapy.

Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis‐driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN‐G) and chemokine ligand 21 (IPMN‐C) are incorporated within microneedles, respectively. The topical application of IPMN‐G and IPMN‐C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN‐G and IPMN‐C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN‐GC is shown as a promising triplatform in engineering transgenic OMV‐incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination‐meditated immunotherapy.

Engineering noble metal‐based electrocatalysts (NMEs) with high activity is of vital importance to accelerate the hydrogen production from proton exchange membrane water electrolyzers (PEMWEs). However, the poor stability and high price of NMEs greatly restrict the practical application. In this review, a series of strategies are summarized to boost the activity and reduce the cost of NMEs under acidic condition from the perspective of composition and structure optimization. The composition regulation through doping of metals or nonmetals can effectively inspire alloy effect or cocktail effect of NMEs, which provides an essential guidance to reduce the cost and enhance the stability of NMEs. Meanwhile, the structure optimization also directly improves the intrinsic activity of NMEs, which is comprehensively elaborated based on size, defect, and geometric effects. In addition, to extend the industrial application of PEMWEs, critical scientific issues behind the formulating of electrocatalyst slurry and coating method–PEMWEs performance relationships are fully clarified. Finally, the challenges for survivability of active center, catalytic mechanism research, and construction of membrane electrode are concluded. This review offers comprehensive and targeted guidelines for the rational design of NMEs for PEMWEs application.

Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

Introduction Exposure of pregnant women and newborns to secondhand smoke (SHS) can lead to adverse maternal and neonatal health outcomes. Among expectant and new fathers, who are the main source of SHS exposure for pregnant women, new mothers and babies, smoking rates remain high. A partner’s pregnancy potentially constitutes a critical period where expectant and new fathers are motivated to quit smoking. However, there is no consensus on the optimal form and delivery of smoking cessation and relapse-prevention interventions. We present a systematic review and network meta-analysis protocol that aims to synthesise and evaluate the effectiveness of smoking cessation and relapse-prevention interventions tailored for this population.Methods and analysis To identify relevant studies, we will conduct a comprehensive search, in English and Chinese, of 10 electronic databases. The review will include randomised and quasi-randomised controlled trials that compare behavioural interventions (tailored and non-tailored) with/without the addition of pharmacotherapy with usual care, a minimal or placebo control for assisting expectant and new fathers to quit smoking and prevent smoking relapse. The primary outcome of interest is the self-reported and/or biochemically verified smoking abstinence at ≥1-month follow-up. Two reviewers will independently screen, select and extract relevant studies, and perform a quality assessment. Disagreements will be resolved by a consensus or third-party adjudication. The Cochrane Risk of Bias tool V.2 will be used to assess the risk of bias in the included studies. We will obtain the results of the systematic review through pooled quantitative analyses using a network meta-analysis. Sensitivity and subgroup analyses will be performed.Ethics and dissemination Ethical approval is not required for this systematic review of published data. The findings will be disseminated via peer-reviewed publication.PROSPERO registration number CRD42022340617.