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Abstract Background This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. Methods This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. Conclusions Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Abstract Cross-linked polymers with covalent adaptable networks (CANs) can be reprocessed under external stimuli owing to the exchangeability of dynamic covalent bonds. Optimization of reprocessing conditions is critical since increasing the reprocessing temperature costs more energy and even deteriorates the materials, while reducing the reprocessing temperature via molecular design usually narrows the service temperature range. Exploiting CO2 gas as an external trigger for lowering the reprocessing barrier shows great promise in low sample contamination and environmental friendliness. Herein, we develop a type of CANs incorporated with ionic clusters that achieve CO2-facilitated recyclability without sacrificing performance. The presence of CO2 can facilitate the rearrangement of ionic clusters, thus promoting the exchange of dynamic bonds. The effective stress relaxation and network rearrangement enable the system with rapid recycling under CO2 while retaining excellent mechanical performance in working conditions. This work opens avenues to design recyclable polymer materials with tunable dynamics and responsive recyclability.

Biodiversity, ecosystems and the services they provide are crucial to the sustainable development of cities, the health and well-being of residents and the maintenance of urban ecological security. The continued decline of global species biodiversity and ecosystem service function has seriously affected the sustainable development of regional social economy. The core of ecological civilization thought is sustainable development, and promoting sustainable development is also the path and means to achieve ecological civilization. As the significant birthplace of ecological civilization thought of “Lucid waters and lush mountains are invaluable assets”, Huzhou has always been committed to creating an “important window” for building an ecological civilization and actively integrating biodiversity conservation into ecological conservation. Through unremitting efforts in recent decades, Huzhou has successfully achieved green sustainable development and reversed the trend of biodiversity loss. Thus, there is a need for a systematic review of successful initiatives in this region and identify the experiences and methods that can advance the sustainable development also in other parts of the world.

Abstract Background Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases. Methods In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%). Conclusions External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation. Trial registration NCT03898895. Registered 2 April 2019.

In bone tissue engineering, polycaprolactone (PCL) is a promising material with good biocompatibility, but its poor degradation rate, mechanical strength, and osteogenic properties limit its application. In this study, we developed an Mg-1Ca/polycaprolactone (Mg-1Ca/PCL) composite scaffolds to overcome these limitations. We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5, 10, and 20 wt%. Porous scaffolds with controlled macro- and microstructure were printed using the fused deposition modeling method. We explored the mechanical strength, biocompatibility, osteogenesis performance, and molecular mechanism of the Mg-1Ca/PCL composites. The 5 and 10 wt% Mg-1Ca/PCL composites were found to have good biocompatibility. Moreover, they promoted the mechanical strength, proliferation, adhesion, and osteogenic differentiation of human bone marrow stem cells (hBMSCs) of pure PCL. In vitro degradation experiments revealed that the composite material stably released Mg2+ ions for a long period; it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth. Microcomputed tomography and histological analysis showed that both 5 and 10 wt% Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects. Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect. Therefore, Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application. Statement of significance: Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects. However, there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds. This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities. Furthermore, the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold. The obtained porous scaffolds can significantly promote the regeneration of bone defects.

Abstract Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate‐stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug‐eluting bead TACE (DEB‐TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first‐order branch of the bile ducts (B1‐type bile duct invasion; B1‐BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB‐TACE with cTACE in this patient population. Materials and Methods Using data from five tertiary medical centers (January 2017–December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1‐BDI who underwent DEB‐TACE or cTACE after successful biliary drainage. X‐tile software calculated the pre‐TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. Results The study included 108 patients with unresectable HCC (B1‐BDI) who underwent DEB‐TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB‐TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB‐TACE group exhibited fewer post‐procedural increments in the mean albumin‐bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p 99 μmol/L) had poorer OS in both groups (p

Introduction: Osteochondral repair poses a significant challenge due to its unique pathological mechanisms and complex repair processes, particularly in bacterial tissue conditions resulting from open injuries, infections, and surgical contamination. This study introduces a biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) designed for osteochondral repair. The scaffold consists of a dicalcium phosphate dihydrate (DCPD)-coated porous magnesium scaffold (DCPD Mg) embedded within a dual crosslinked sodium alginate hydrogel (Zn-AlgMA). This combination aims to synergistically exert antibacterial and osteochondral integrated repair properties.Methods: The Zn-AlgMA@Mg scaffold was fabricated by coating porous magnesium scaffolds with DCPD and embedding them within a dual crosslinked sodium alginate hydrogel. The structural and mechanical properties of the DCPD Mg scaffold were characterized using scanning electron microscopy (SEM) and mechanical testing. The microstructural features and hydrophilicity of Zn-AlgMA were assessed. In vitro studies were conducted to evaluate the controlled release of magnesium and zinc ions, as well as the scaffold’s osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis was performed to elucidate the mechanism of osteochondral integrated repair. In vivo efficacy was evaluated using a rabbit full-thickness osteochondral defect model, with micro-CT evaluation, quantitative analysis, and histological staining (hematoxylin-eosin, Safranin-O, and Masson’s trichrome).Results: The DCPD Mg scaffold exhibited a uniform porous structure and superior mechanical properties. The Zn-AlgMA hydrogel displayed consistent microstructural features and enhanced hydrophilicity. The Zn-AlgMA@Mg scaffold provided controlled release of magnesium and zinc ions, promoting cell proliferation and vitality. In vitro studies demonstrated significant osteogenic and chondrogenic properties, as well as antibacterial efficacy. Proteomic analysis revealed the underlying mechanism of osteochondral integrated repair facilitated by the scaffold. Micro-CT evaluation and histological analysis confirmed successful osteochondral integration in the rabbit model.Discussion: The biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) demonstrated promising results for osteochondral repair, effectively addressing the challenges posed by bacterial tissue conditions. The scaffold’s ability to release magnesium and zinc ions in a controlled manner contributed to its significant osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis provided insights into the scaffold’s mechanism of action, supporting its potential for integrated osteochondral regeneration. The successful in vivo results highlight the scaffold’s efficacy, making it a promising biomaterial for future applications in osteochondral repair.

IntroductionWith women's advancement in education and status, they drive corporate and social progress. However, traditional gender roles burden female employees with more family responsibilities, challenging work-life balance and affecting job performance. Organizations should supporting female employees to address these challenges. Thriving at work, a core aspect of positive work engagement, helps maintain enthusiasm and efficiency. This study explores the impact of family-supportive supervisor behavior (FSSB) on the thriving at work of female employees in China, considering generational differences in their work-family balance needs and the mediating mechanisms involved.MethodsThe methodology adopted in this study utilized Amos 26.0 and SPSS 25.0 to analyze data obtained from a sample of 279 female employees in China. Specifically, the study examined the direct impact of FSSB on thriving at work, alongside the mediating influence of work-family balance. Moreover, the research aimed to discern variations in these effects across different generational cohorts.ResultsThis study highlights the direct impact of FSSB on female employees' thriving at work across different generational cohorts. Notably, the “post-90s” generation displayed the strongest direct effect of FSSB on thriving at work. Additionally, the impact of FSSB on work-family balance varied by generation, with the “post-90s” generation showing the weakest effect. Furthermore, the mediating role of work-family balance differed among generations, with complete mediation observed in the “post-80s” generation but no mediating effect in the “post-90s” generation, reflecting their distinct work-life balance priorities and needs.DiscussionThis study uses a generational difference perspective to explore the main and mediating effects of FSSB on thriving at work, enriching the theoretical research on generational differences and providing valuable insights for future research. Practically, organizations should focus on the needs of different generations while encouraging FSSB, fostering a supportive work environment and enhancing outcomes.

Tumor-infiltrating immune cells (TICs) play a central role in the tumor microenvironment, which can reflect the host anti-tumor immune response. However, few studies have explored TICs in predicting the prognosis of lung adenocarcinoma (LUAD). In our study, we enrolled 2470 LUAD patients from TCGA and GEO databases, and the normalized enrichment scores for 65 immune cell types were quantified for each patient. An immune-related risk score (IRRS) was built on the basis of 17 selected TICs using LASSO regression analysis, and the results showed that high-risk patients were correlated with shorter survival time for the LUAD cohorts. Correlation analyses between IRRS and clinical characteristics were also evaluated to validate the clinical use of IRRS. In addition, we analyzed the differences in the distribution of immune cell infiltration and immunoregulatory gene expression, which may facilitate individual immunotherapy. Based on the above result, we conclude that IRRS can act as a powerful predictor for risk stratification and prognosis prediction, and may facilitate the decision-making process for LUAD patients.

Abstract Background Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current “gold standard” treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 μg/kg) to test its biological activity. Results An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines. Conclusion The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.

Abstract Developing atomically synergistic bifunctional catalysts relies on the creation of colocalized active atoms to facilitate distinct elementary steps in catalytic cycles. Herein, we show that the atomically-synergistic binuclear-site catalyst (ABC) consisting of $${{{{{\rm{Zn}}}}}}^{\delta+}$$ Zn δ + -O-Cr6+ on zeolite SSZ-13 displays unique catalytic properties for iso-stoichiometric co-conversion of ethane and CO2. Ethylene selectivity and utilization of converted CO2 can reach 100 % and 99.0% under 500 °C at ethane conversion of 9.6%, respectively. In-situ/ex-situ spectroscopic studies and DFT calculations reveal atomic synergies between acidic Zn and redox Cr sites. $${{{{{\rm{Zn}}}}}}^{\delta+}$$ Zn δ + ( $$0 \, < \, \delta \, < \, 2$$ 0 < δ < 2 ) sites facilitate β-C-H bond cleavage in ethane and the formation of Zn-H δ- hydride, thereby the enhanced basicity promotes CO2 adsorption/activation and prevents ethane C-C bond scission. The redox Cr site accelerates CO2 dissociation by replenishing lattice oxygen and facilitates H2O formation/desorption. This study presents the advantages of the ABC concept, paving the way for the rational design of novel advanced catalysts.

Abstract The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6–8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.

ObjectivesTo investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa).MethodsWe performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance.ResultsPPAT and normalized PPAT were associated with BM (P

Highlights A unique atomic dispersed hetero-pair was successfully synthesized, consisting of Mo-Fe di-atoms anchored on N-doped carbon carrier. This strategy breaks the linear scaling relationships of electrocatalytic CO2 reduction by simultaneously regulating the *COOH adsorption energy and *CO desorption energy. The as-prepared MoFe–N–C exhibits excellent performance for CO2RR to CO with a high turnover frequency (TOF) of 3336.21 h−1, CO Faradaic efficiency (FECO) of 95.96% at − 0.60 V (versus RHE) and outstanding stability.

Based on the analytic hierarchy process, an evaluation index system consisting of 3 first-level indexes and 15 second-level indexes was established. The tracking evaluation of marine environmental impact during construction was carried out in three offshore wind farms in Zhuhai, Yangjiang and Shantou, using the evaluation method based on data analysis, which was the first application in this field. The evaluation content covered the qualitative analysis of the environmental management status of the offshore wind power project during the construction period and the implementation of environmental countermeasures as well as the quantitative evaluation of the ecological environmental impact. The comprehensive evaluation results were obtained, and the existing problems and countermeasures were clarified. At the same time, it was suggested to explore the implementation of the whole process of marine environmental impact assessment system, further reduced the impact of engineering construction on the marine environment, and jointly promoted high-quality economic development and high-level protection of ecological environment.

In oncolytic virus (OV) therapy, a critical component of tumor immunotherapy, viruses selectively infect, replicate within, and eventually destroy tumor cells. Simultaneously, this therapy activates immune responses and mobilizes immune cells, thereby eliminating residual or distant cancer cells. However, because of OVs’ high immunogenicity and immune clearance during circulation, their clinical applications are currently limited to intratumoral injections, and their use is severely restricted. In recent years, numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection. The most commonly used nanomaterials for modifying OVs are liposomes, polymers, and albumin, because of their biosafety, practicability, and effectiveness. The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

Abstract Noble metals supported on reducible oxides, like CoOx and TiOx, exhibit superior activity in many chemical reactions, but the origin of the increased activity is not well understood. To answer this question we studied thin films of CoOx supported on an Au(111) single crystal surface as a model for the CO oxidation reaction. We show that three reaction regimes exist in response to chemical and topographic restructuring of the CoOx catalyst as a function of reactant gas phase CO/O2 stoichiometry and temperature. Under oxygen-lean conditions and moderate temperatures (≤150 °C), partially oxidized films (CoOx1) forms containing Co3+ species that are effective in a wide temperature range. Resonant photoemission spectroscopy (ResPES) revealed the unique role of Co3+ sites in catalyzing the CO oxidation. Density function theory (DFT) calculations provided deeper insights into the pathway and free energy barriers for the reactions on these oxide phases. These findings in this work highlight the versatility of catalysts and their evolution to form different active phases, both topological and chemically, in response to reaction conditions exposing a new paradigm in the catalyst structure during operation.

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.

IntroductionThis study examines the optimum conversion of Wuzhishan pig manure by Black Soldier Fly Larvae (BSFL) at various phases of development, as well as the impact of gut microbiota on conversion efficiency.Method and resultsIn terms of conversion efficiency, BSFL outperformed the growing pig stage (GP) group, with significantly higher survival rates (96.75%), fresh weight (0.23 g), and larval conversion rate (19.96%) compared to the other groups. Notably, the GP group showed significant dry matter reductions (43.27%) and improved feed conversion rates (2.17). Nutritional composition varied, with the GP group having a lower organic carbon content. High throughput 16S rRNA sequencing revealed unique profiles, with the GP group exhibiting an excess of Lactobacillus and Clostridium. Promising cellulose-degrading bacteria in pig manure and BSFL intestines, including Bacillus cereus and Bacillus subtilis, showed superior cellulose degradation capabilities. The synergy of these thermophilic bacteria with BSFL greatly increased conversion efficiency. The BSFL1-10 group demonstrated high growth and conversion efficiency under specific conditions, with remarkable larval moisture content (71.11%), residual moisture content (63.20%), and waste reduction rate (42.28%).DiscussionThis study sheds light on the optimal stages for BSFL conversion of pig manure, gut microbiota dynamics, promising thermophilic cellulose-degrading bacteria, and the significant enhancement of efficiency through synergistic interactions. These findings hold great potential for sustainable waste management and efficient biomass conversion, contributing to environmental preservation and resource recovery.

Studies have probed nanoplastic toxicity on environmental organisms, but the regulatory role of animal PIEZO-type mechanosensitive ion channel component (PIEZO) remains unclear. Herein, we identified the sole PIEZO in Caenorhabditis elegans (C. elegans), utilizing amino acid homology analysis and Trans-Membrane prediction using Hidden Markov Models (TMHMM). In C. elegans, RNAi knockdown of pezo-1 had no impact on lifespan, body length, lethality, locomotion behaviors, or oxidative response (P > 0.05). However, exposure to 15 μg/L nanopolystyrene in the pezo-1 RNAi group resulted in severe locomotion changes: head trashes (P

In densely populated, highly urbanized regions such as Zhejiang Province (eastern China), species are under enormous environmental pressures resulting from human activities, land use changes, and habitat fragmentation, which affect species composition and species diversity. Although eastern China is one of the most concentrated distribution areas of endemic bryophytes in East Asia, these species are also faced with the threats of habitat inadequacy. In order to get more information on bryophyte habitat and diversity, we investigated species composition, habitat preference, as well as species diversity differences of bryophytes under different habitat conditions in Jiulongshan National Forest Park (JNFP). In particular, the results showed that 108 specimens of bryophyte were collected in total, including 46 species in 32 genera of 21 families. Furthermore, we had found 12 species of bryophytes that had never been recorded before in Zhejiang Province. Remarkably, 40.74% of bryophytes were found to grow on natural rocks, followed by understories and roadside habitats. In addition, the Patrick richness index (R) varied most significantly among different habitats (p

Self-healing elastomers provide extended longevity of functional materials, due to their unique adaptability and durability. However, a major scientific challenge remains in developing materials with a rapid healing process combined with decent mechanical properties, that can be prepared by a relatively simple synthesis approach. Herein, we report a versatile design approach on self-healing elastomers by incorporating two different hydrogen bonding containing monomers, i.e., 2-[[(butylamino)carbonyl]oxy]ethyl acrylate (BCOE) and 2-ureido-4[1H]pyrimidinone (UPy) functionalized ethyl methacrylate. Poly(BCOE-r-UPy)s are synthesized by reversible addition−fragmentation chain-transfer (RAFT) polymerization, and controlling the ratio of two monomers enables well-tunable mechanical properties with tensile strength ranging from 0.04 to 6.3 MPa and tensile strain up to 3,000 %. The characteristic dissociation energy is calculated from a temperature dependence of terminal relaxation followed by subtracting the segmental relaxation. The rapid autonomous self-healing is achieved when the molar composition of Poly(BCOE-r-UPy) is tailored to BCOE/UPy = 99/1. The self-healing process is monitored in situ by a helium-ion microscope, and its macroscopic study using tensile tests indicates that Poly(BCOE-r-UPy1) with 1 % molar ratio of UPy recovers 70 % of its original toughness at ambient temperature within 10 mins. 3D printing of Poly(BCOE-r-UPy) affords a self-healable 3D structure, demonstrating the adaptability of Poly(BCOE-r-UPy) for on-demand fabrication. The simplicity of synthesis, well-tunable mechanical properties, unique self-healability, and 3D printing capability of Poly(BCOE-r-UPy)s indicate their potential for a range of applications.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5 cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholin’s gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patient’s disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease.

There are plans to set up a space-based gravitational wave observatory that will use an ultra-large-scale laser interferometer in space to detect medium- and low-frequency gravitational waves. Both heliocentric and geocentric formations adopt the method of launching three satellites with one rocket, which has high requirements in terms of the carrying capacity of the rocket. Therefore, a proper transfer design is a prerequisite for achieving space-based gravitational wave detection. In this paper, the transfer orbit for three satellites of the Taiji mission is designed based on the two-impulse transfer model. Moreover, the influence on orbit design of the position of the formation relative to Earth, the initial phase angle of the formation, and the initial time of transfer is analyzed. The Earth-leading and -trailing transfers show opposite patterns in the above three aspects. A smaller velocity increment is required if a proper initial time is selected. After taking into account the stability of the formation, C3, the required velocity increment, transfer time, and the distance to Earth, 20° is determined to be the optimal initial trailing/leading angle.

In this paper, we demonstrate the significant impact of the solution flow and electrical field on the homogeneity of large-scale ZnO nanorod electrodeposition from an aqueous solution containing zinc nitrate and ammonium nitrate, primarily based on the X-ray fluorescence results. The homogeneity can be enhanced by adjusting the counter electrode size and solution flow rate. We have successfully produced relatively uniform nanorod arrays on an 8 × 10 cm2 i-ZnO-coated fluorine-doped tin oxide (FTO) substrate using a compact counter electrode and a vertical stirring setup. The as-grown nanorods exhibit similar surface morphologies and dominant, intense, almost uniform near-band-edge emissions in different regions of the sample. Additionally, the surface reflectance is significantly reduced after depositing the ZnO nanorods, achieving a moth-eye effect through subwavelength structuring. This effect of the nanorod array structure indicates that it can improve the utilization efficiency of light reception or emission in various optoelectronic devices and products. The large-scale preparation of ZnO nanorods is more practical to apply and has an extremely broad application value. Based on the research results, it is feasible to prepare large-scale ZnO nanorods suitable for antireflective coatings and commercial applications by optimizing the electrodeposition conditions.

Abstract Micro-nano biorobots based on bacteria have demonstrated great potential for tumor diagnosis and treatment. The bacterial gene expression and drug release should be spatiotemporally controlled to avoid drug release in healthy tissues and undesired toxicity. Herein, we describe an alternating magnetic field-manipulated tumor-homing bacteria developed by genetically modifying engineered Escherichia coli with Fe3O4@lipid nanocomposites. After accumulating in orthotopic colon tumors in female mice, the paramagnetic Fe3O4 nanoparticles enable the engineered bacteria to receive and convert magnetic signals into heat, thereby initiating expression of lysis proteins under the control of a heat-sensitive promoter. The engineered bacteria then lyse, releasing its anti-CD47 nanobody cargo, that is pre-expressed and within the bacteria. The robust immunogenicity of bacterial lysate cooperates with anti-CD47 nanobody to activate both innate and adaptive immune responses, generating robust antitumor effects against not only orthotopic colon tumors but also distal tumors in female mice. The magnetically engineered bacteria also enable the constant magnetic field-controlled motion for enhanced tumor targeting and increased therapeutic efficacy. Thus, the gene expression and drug release behavior of tumor-homing bacteria can be spatiotemporally manipulated in vivo by a magnetic field, achieving tumor-specific CD47 blockage and precision tumor immunotherapy.

Robot dexterous hand can mimic human movements to realize multiple tasks in complex scenarios, which is a key technology for developing intelligent humanoid robots. Focusing on the research history of robotic dexterity, the current research status of multi-fingered dexterity is elaborated, and the evolution process and research progress of dexterity are analyzed. The classification and characteristics of dexterous hands are discussed in terms of the number of degrees of freedom, drive mode, mechanical transmission mode and sensing technology, and the future development trend of dexterous hands is envisioned.

Conventional voxel-based algorithms for labeling connected components in 3D binary images use the same mask to process all object voxels. To reduce the number of times that neighboring voxels are checked when object voxels are processed, we propose an algorithm that uses two different masks for processing two different types of object voxels. One type of mask is used when the voxel preceding the object voxel being processed is an object voxel, and the other type is used otherwise. In either case, an optimal order is used for checking the voxels in the corresponding mask. Experimental results demonstrate that our proposed algorithm checked fewer voxels, and was more efficient than conventional algorithms.

The aim of this study was to investigate the effect of different prebiotic (inulin, fructooligosaccharides, and galactooligosaccharides) on textural, rheological, and microstructural properties of synbiotic yogurt. The results showed that synbiotic yogurt group fortified with inulin could significantly improve the water holding capacity and hardness (P

Research about farmland pollution by heavy metals/metalloids in China has drawn growing attention. However, there was rare information on spatiotemporal evolution and pollution levels of heavy metals in the major grain-producing areas. We extracted and examined data from 276 publications between 2010 and 2021 covering five major grain-producing regions in China from 2010 to 2021. Spatiotemporal evolution characteristics of main heavy metals/metalloids was obtained by meta-analysis. In addition, subgroup analyses were carried out to study preliminary correlations related to accumulation of the pollutants. Cadmium (Cd) was found to be the most prevailing pollutant in the regions in terms of both spatial distribution and temporal accumulation. The Huang-Huai-Hai Plain was the most severely polluted. Accumulation of Cd, mercury (Hg) and copper (Cu) increased from 2010 to 2015 when compared with the 1990 background data. Further, the levels of five key heavy metals (Cd, Cu, Hg, lead [Pb] and zinc [Zn]) showed increasing trends from 2016 to 2021 in all five regions. Soil pH and mean annual precipitation had variable influences on heavy metal accumulation. Alkaline soil and areas with less rainfall faced higher pollution levels. Farmlands cropped with mixed species showed smaller effect sizes of heavy metals than those with single upland crop, suggesting that mixed farmland use patterns could alleviate the levels of heavy metals in soil. Of various soil remediation efforts, farmland projects only held a small market share. The findings are important to support the research of risk assessment, regulatory development, pollution prevention, fund allocation and remediation actions.

We sorted the waste from mechanical processing to form recycled steel fibers. In order to study the flexural mechanical properties of reinforced concrete beams after the addition of recycled steel fibers, four recycled steel fiber concrete beams (RSFCBs) and one normal concrete beam (NCB) were designed and poured using the volume fraction of steel fibers (0%, 0.5%, 1%, 1.5%, 2%) as the variables. Normal section bending tests were conducted on them under a concentrated load. We obtained experimental data such as the cracking load, ultimate load, mid-span deflection, and steel and concrete strain of the beam by gradually loading the test beam, and we observed and recorded the development of cracks. The results indicate that the NCB exhibits crushing failure, while the RSFCBs exhibit equilibrium failure. The addition of recycled steel fibers effectively controls the extension of cracks, resulting in a better bending toughness of the beam. The bending performance of RSFCBs with different volume additions shows a trend of first increasing and then decreasing with the increase in steel fiber content. The peak value was reached when the steel fiber content was 1.5%, which increased the bending bearing capacity by 54.72% compared with the NCB. With the increase in steel fiber content, the required load value for tensile steel bars to yield also increases, reaching a peak at a content of 1.5%, which increases the bending bearing capacity by 44.64% compared with the NCB. The addition of recycled steel fibers enables the beam to improve its bearing capacity while limiting the development of longitudinal reinforcement strain, allowing the longitudinal reinforcement to yield under higher loads and improving the overall bending performance of the beam.

Abstract Tough hydrogel has attracted considerable interest in various fields, however, due to poor biocompatibility, nondegradation, and pronounced compositional differences from natural tissues, it is difficult to be used for tissue regeneration. Here, a gelatin‐based tough hydrogel (GBTH) is proposed to fill this gap. Inspired by human exercise to improve muscle strength, the synergistic effect is utilized to generate highly functional crystalline domains for resisting crack propagation. The GBTH exhibits excellent tensile strength of 6.67 MPa (145‐fold that after untreated gelation). Furthermore, it is directly sutured to a ruptured tendon of adult rabbits due to its pronounced toughness and biocompatibility, self‐degradability in vivo, and similarity to natural tissue components. Ruptured tendons can compensate for mechanotransduction by GBTH and stimulate tendon differentiation to quickly return to the initial state, that is, within eight weeks. This strategy provides a new avenue for preparation of highly biocompatible tough hydrogel for tissue regeneration.

The rapid display and delivery method for customized tumor mRNA vaccines is limited. Herein, bacteria-derived outer membrane vesicles (OMVs) are employed as an mRNA delivery platform by surface engineering of an RNA-binding protein, L7Ae. OMV-L7Ae can rapidly adsorb boxC/D sequence-labeled mRNA antigens through L7Ae-boxC/D binding and deliver them into HEK-293T and dendritic cells. This platform provides an mRNA delivery technology distinct from lipid nanoparticles (LNPs) for personalized mRNA tumor vaccination and with a Plug-and-Display strategy suitable for rapid preparation of the personalized mRNA tumor vaccine against varied tumor antigens.Key features• OMVs are employed as an mRNA delivery platform through L7Ae-boxC/D binding.Graphical overview

Recently, bacteria‐mediated therapy has been widely applied for tumor treatments owing to some inherent features of bacteria. With further advancements in genetic engineering and nanotechnology, natural bacteria are endowed with extra capacities of rational genetic reprogramming, spatiotemporally precise manipulation, and some other exogenous characteristics. Hybrid bacteria systems leverage versatile nanomaterials to modify the surface of bacteria, which exhibit great potential in solving the existed problems of traditional bacteria therapy, further greatly improving the tumor therapeutic efficacy. Therefore, hybrid bacteria–based therapeutic platforms present a promising strategy for tumor therapy, which raise increasing attentions. In this review, hybrid bacteria systems for tumor therapy based on different types of chassis bacteria and other related organisms are introduced, and methodologies of nanomaterial‐modified bacteria are systemically expounded. Moreover, the promises of hybrid bacteria as drug delivery vesicles for cancer therapy, other disease therapy, bioimaging, and diagnosis are further discussed, followed by the elaboration on their perspectives and challenges in clinical translation.

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.

Abstract The aim of this study was to investigate the prevalence, correlation, and differences of C-shaped root canals (CSRCs) morphology in permanent mandibular premolars and molars in Eastern Chinese individuals using cone-beam computed tomography (CBCT). A total of 8000 mandibular first premolars (MFPs), mandibular second premolars (MSPs), mandibular first molars (MFMs), and mandibular second molars (MSMs) CBCT images from 1000 patients (692 females and 308 males) were collected. The prevalence, correlation, bilateral/unilateral presence, the morphology of CSRCs, level of canal bifurcation, gender differences, and location of radicular grooves (RGs) were evaluated. The prevalence of CSRCs in MFPs, MSPs, MFMs and MSMs were 10.25%, 0.25%, 0.55% and 47.05%, respectively. The prevalence of CSRCs in MFPs of males was higher than that in females, while the prevalence of CSRCs in MSMs of females was higher than that in males (P

Abstract Background Guided endodontics is a successful technique that has been gradually applied to endodontic therapy in recent years without being affected by the operator’s experience. However, the guided bur produces excessive heat during continuous rotation and friction with root canal walls, it is not clear whether the degree of temperature increase may lead to the periodontal ligament and alveolar bone damage. Methods A total of 58 teeth were used, of which 40 teeth were not grouped, all used to evaluate the accuracy. 40 single-rooted premolars were scanned using CBCT and an intra-oral scanner, and 3D-printed guided plates were made with the pre-designed access. A custom-made guided bur was used to prepare the access cavities. The postoperative CBCT data and pre-designed pathways were matched to evaluate the deviation between the planned and virtual paths. The other 18 teeth were randomly divided into three groups (ET20 and ProTaper F3 as the control group, guided endodontics as the test group), with 6 teeth in each group. The temperature changes on the root surfaces were inspected with a thermocouple thermometer. Results The average deviation on the tip and the base of the bur was 0.30 mm and 0.28 mm (mesial/distal), and 0.28 mm and 0.25 mm (buccal/lingual). The average angle deviation was 3.62°. The mean root surface temperature rise of the guided endodontics group was the lowest (5.07 °C) (P

The unbalanced industrial development in Beijing, Tianjin and Hebei leads to the economic development with increasingly prominent environmental problems, which is not conducive to the coordinated development of Beijing, Tianjin and Hebei. This research constructs a composite multiple mediation model with government factors as independent variables, market factors, technological innovation, and location factors as mediating variables, and coordinated development as outcome variables to conduct an empirical study. The PLS-SEM method was used to evaluate and test the initial model and the modified model. After several fittings, the optimal model is obtained, the study found that the mediating effect value of technological innovation was the largest between government factors to coordinated development effects, followed by the mediating variables location factors and market factors. It is recommended to build a common research and sharing mechanism for green technological innovation in pollution reduction and accelerate the speed of transformation of green achievements; build an internal and external construction mechanism based on thermal power and other high haze pollution industrial systems to improve the proportion of high quality population; build a financial hierarchical expenditure guarantee mechanism and strive to create an environment open to foreign business.

Sugar transporters are essential for osmotic process regulation, various signaling pathways and plant growth and development. Currently, few studies are available on the function of sugar transporters in sorghum (Sorghum bicolor L.). In this study, we performed a genome-wide survey of sugar transporters in sorghum. In total, 98 sorghum sugar transporters (SSTs) were identified via BLASTP. These SSTs were classified into three families based on the phylogenetic and conserved domain analysis, including six sucrose transporters (SUTs), 23 sugars will eventually be exported transporters (SWEETs), and 69 monosaccharide transporters (MSTs). The sorghum MSTs were further divided into seven subfamilies, including 24 STPs, 23 PLTs, two VGTs, four INTs, three pGlcT/SBG1s, five TMTs, and eight ERDs. Chromosomal localization of the SST genes showed that they were randomly distributed on 10 chromosomes, and substantial clustering was evident on the specific chromosomes. Twenty-seven SST genes from the families of SWEET, ERD, STP, and PLT were found to cluster in eight tandem repeat event regions. In total, 22 SSTs comprising 11 paralogous pairs and accounting for 22.4% of all the genes were located on the duplicated blocks. The different subfamilies of SST proteins possessed the same conserved domain, but there were some differences in features of the motif and transmembrane helices (TMH). The publicly-accessible RNA-sequencing data and real-time PCR revealed that the SST genes exhibited distinctive tissue specific patterns. Functional studies showed that seven SSTs were mainly located on the cell membrane and membrane organelles, and 14 of the SSTs could transport different types of monosaccharides in yeast. These findings will help us to further elucidate their roles in the sorghum sugar transport and sugar signaling pathways.

Tumor vaccines, a type of personalized tumor immunotherapy, have developed rapidly in recent decades. These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells. Because the immunogenicity of tumor antigens alone is insufficient, immune adjuvants and nanocarriers are often required to enhance anti-tumor immune responses. At present, vaccine carrier development often integrates nanocarriers and immune adjuvants. Among them, outer membrane vesicles (OMVs) are receiving increasing attention as a delivery platform for tumor vaccines. OMVs are natural nanovesicles derived from Gram-negative bacteria, which have adjuvant function because they contain pathogen associated molecular patterns. Importantly, OMVs can be functionally modified by genetic engineering of bacteria, thus laying a foundation for applications as a delivery platform for tumor nanovaccines. This review summarizes 5 aspects of recent progress in, and future development of, OMV-based tumor nanovaccines: strain selection, heterogeneity, tumor antigen loading, immunogenicity and safety, and mass production of OMVs.

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug’s approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects. However, typical resorbable membranes composed of collagen (Col) have insufficient mechanical properties and high degradation rate, while non-resorbable membranes need secondary surgery. Herein, we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium (Col/PCLMA/Mg) composite membrane that provided spatiotemporal support effect after photocrosslinking. Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed; Col membranes and PCL membranes were used as controls. After photocrosslinking, an interpenetrating polymer network was observed by scanning electron microscopy (SEM) in Col/PCL and Col/PCL/Mg membranes. The elastic modulus, swelling behavior, cytotoxicity, cell attachment, and cell proliferation of the membranes were evaluated. Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM. The membranes were implanted into calvarial bone defects of rats for 8 weeks. The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus (p 0.05). The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes, both in vivo and in vitro (p

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice.Methods: Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. In vitro, steatotic L-02 cells were used to explore the underlying mechanism.Results: In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells.Conclusion: Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes.

Sanwei sandalwood decoction (SWTX) is a classical Chinese medicine formula and clinically effective treatment for coronary heart disease, including myocardial ischemia/reperfusion (I/R) injury. Because the treatment mechanism of SWTX in I/R injury remains obscure, we intended to analyze the potential cardioprotective effects of SWTX in rats with myocardial I/R injury. Our research revealed that SWTX prolonged ventricular conduction time in a dose-dependent manner. While SWTX significantly delayed left ventricular signal conduction velocity, it had no effect on left atrial conduction velocity. Under sinus conditions, low SWTX concentrations reduced left ventricular conduction dispersion, while high concentrations increased conduction dispersion. SWTX also prolonged the QRS interval, APD30/50/90, and ERP. In whole-cell patch clamp experiments on myocytes, Ito and Ikr were inhibited by SWTX. While SWTX had no effect on INa, the activation curve for Nav1.5 was left-shifted. Finally, SWTX reduced the probability of ventricular fibrillation and suppressed early and late depolarization in an acute I/R injury rat model. These findings shed light on the mechanism by which SWTX alleviates myocardial I/R injury.

Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.

Milk protein is an important component in milk and dairy products, and its content and composition are important factors influencing the functionality of milk such as nutrition and immunity. Protein components in milk are complex, and the content of different components varies greatly. With the development of functional properties of milk protein, it is of great significance and value to determine the content of milk protein components in a faster and more accurate way. Currently, enzyme-linked immunosorbent assay (ELISA), capillary electrophoresis (CE), high performance liquid chromatography (HPLC) and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) are the main methods used to determine protein components in milk. In this article, the measurement principle, applicability, and the characteristics of these methods are reviewed, which could provide reliable technical reference for accurate measurement and establishment of a novel method in milk protein evaluation, while this could also be a theoretical support for dairy nutrition research, development of dairy products and infant formula optimization.

Light Non-Aqueous Phase Liquids (LNAPLs) in vadose zone is of multi-phase characteristics, while factors such as heterogeneity and groundwater fluctuation are expected to significantly increase the complexity of LNAPLs contamination in vadose zone. Previous studies have mostly focused on revealing the contamination process of free-phase LNAPLs, few have explored deeply the influence of the heterogeneous structure on the migration and phase distribution pattern of LNAPLs when the water table fluctuates. A numerical model of multiphase flow in vadose zone is established based on TOUGH2 to reveal the migration and phase distribution of LNAPLs under the joint effect of different lithological lenses and water table fluctuation. The results show that (1) the migration and distribution regularity of LNAPLs in vadose zone is predominantly controlled by the variation in water content, which is presented under the effect of heterogeneity and water fluctuation. (2) In the steady groundwater scenario, LNAPL migrates in an “accumulation-lateral expansion-flow bypass” pattern around the fine-sand lens, while the coarse-sand lens acts as the "preferential route" for the vertical movement of LNAPL. Flow around the fine-sand lens is significantly enhanced by the variation in water content induced by groundwater fluctuation, and the coarse-sand lens further exhibits the "preferential space" effect. (3) When the water table is steady, LNAPL are concentrated inside and below the lens body in the fine-sand and coarse-sand lens models, respectively. In the fluctuating groundwater scenario, a greater range of LNAPL is presented in the vicinity of the lens with the distribution area in each model is 51% and 63% larger than that in the steady scenario. (4) Volatile flux of LNAPL, affected by the LNAPL-gas exposure conditions and the distribution of LNAPL, shows a "decreasing-then increasing" pattern in both models. The three-phase equilibrium state is disrupted by groundwater fluctuation, which is manifested by the enhanced volatilization during the stage of groundwater elevation, when the average volatile flux in the two models is 124%～126% higher compared to the steady scenario.This research provides a theoretical basis for the understanding of LNAPL pollution process in heterogeneous contaminated sites.

Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen, thus efficiently facilitating antitumor adaptive immunity. Bacteria-derived outer membrane vesicles (OMVs) are an excellent candidate due to their abundance of pathogen associated molecular patterns. However, during the uptake of OMVs by dendritic cells (DCs), the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage, a phenomenon we refer to as “maturation-induced uptake obstruction” (MUO). Herein we decorated OMV with the DC-targeting αDEC205 antibody (OMV-DEC), which endowed the nanovaccine with an uptake mechanism termed as “not restricted to maturation via antibody modifying” (Normandy), thereby overcoming the MUO phenomenon. We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display. In summary, this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines, and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.