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Abstract Objective This research analyzes the potential of long non-coding RNAs (lncRNAs) as markers in determining the necessity of antiviral treatment in pregnant women by examining alterations in the expression profile of serum lncRNAs in pregnant women with elevated hepatitis B viral load (HBVL) under antiviral and non-antiviral treatment regimens between the second trimester and delivery. Methods Serum was obtained from 6 s-trimester pregnant women with high HBVL and no intrauterine infection. Then, 3 of these women were randomly selected for antiviral treatment, with the remaining 3 women undergoing non-antiviral treatment as control. Serum samples were again collected from these 6 women before delivery. The expression profile of lncRNAs was analyzed with microarray technology, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The axes of hub lncRNA-miRNA-mRNA were identified based on the competing endogenous RNA (ceRNA) network. Results The expression profile of serum lncRNAs in pregnant women with high HBVL changed significantly from the second trimester of pregnancy until delivery under antiviral or non-antiviral treatment. The Venn diagram was utilized to screen out the jointly up-regulated and down-regulated lncRNAs in the serum of pregnant women under antiviral and non-antiviral treatment before delivery. Additionally, the KEGG pathway enrichment analysis results showed that lncRNAs might mediate the Hippo pathway in HBV infection. Based on the ceRNA network, 3 hub lncRNAs (CATG00000076041.1, LINC01310, and G014655) were found to potentially regulate the key gene TP73 in the Hippo pathway. Conclusion In this study, we retrieved co-differentially expressed lncRNAs in pregnant women with high HBVL under antiviral or non-antiviral treatment, which may be used as markers for evaluating whether pregnant women with high HBVL may be free of antiviral treatment. This study may provide a basis for preventing potential adverse effects of antiviral treatment on maternal and fetal health.

【Objective】Real-time quantitative PCR is one of the most conventional and efficient techniques for studying the mRNA expression level of target genes. The proper selection of reference genes is of great significance for the accuracy of the results. The study aimed to identify the most suitable reference genes by evaluating the expression stability of candidate reference genes in different samples of Spodoptera frugiperda larvae under azadirachtin stress. The results provided a basis for functional analysis of target genes and molecular toxicological mechanism analysis of azadirachtin.【Method】Eight candidate reference genes, including α-TUB, β-1-TUB, Actin, EF1α, EF2, GAPDH, RPL3 and RPL3, of S. frugiperda were selected. The expression stability of these genes in different samples of larvae, cuticle, midgut, fat body and malpighian tube under azadirachtin stress was evaluated by the ΔCt, GeNorm, NormFinder, BestKeeper and RefFinder software. And the optimal number of reference genes were determined by GeNorm software. Finally, the best reference gene combinations in different samples were comfirmed.【Result】When exposed to azadirachtin stress, in larvae samples, the expression stability of α-TUB and β-1-TUB was the highest by ΔCt and Normfinder analyses; the expression stability of RPL3 and RPL13 was the highest by GeNorm analysis; and the expression stability of α-TUB and RPL13 was the highest by BestKeeper analysis. In cuticle samples, β-1-TUB and α-TUB were rated as the most stable genes in ΔCt, GeNorm and Normfinder, while Actin and β-1-TUB were the most stable in BestKeeper. In the midgut tissue, ΔCt analysis found that EF2 and β-1-TUB expression was the most stable; GeNorm assessment showed that EF1α and RPL3 expression was the most stable; Normfinder considered that EF2 and β-1-TUB expression was the most stable, and BestKeeper analysis found that RPL13 and RPL3 expression was the most stable. ΔCt, GeNorm and Normfinder analyses showed that RPL3 and EF1α were the most stable in fat body tissue, while BestKeeper analysis showed that RPL13 and RPL3 were the most stable. In malpighian tube tissue, ΔCt analysis found that RPL3 and EF2 expression was the most stable, GeNorm assessment indicated that EF1α and EF2 expression was the most stable; Normfinder considered that β-1-TUB and EF2 expression was the most stable, and BestKeeper analysis found that RPL13 and β-1-TUB expression was the most stable. In addition, GeNorm software analysis found that the optimal number of reference genes in each sample was 2. Therefore, as assessed by RefFinder comprehensive analysis, α-TUB and β-1-TUB had the highest expression stability in larvae and cuticle tissue samples; EF2 and RPL3 had the highest expression stability in larval midgut and malpighian tube samples; and RPL3 and EF1α had the highest expression stability in fat body samples.【Conclusion】Under azadirachtin stress, the optimal reference genes for different samples of S. frugiperda larvae were shown as: α-TUB and β-1-TUB for larvae and cuticle samples; EF2 and RPL3 for midgut and malpighian tube samples; and RPL3 and EF1α for fat body samples.

ObjectiveTo investigate the association between piano playing and myopia prevalence, and to analyze the interactive effect of piano playing and outdoor activity time or out-of-class study time on myopia among primary and secondary school students in Shanghai. MethodsVisual acuity tests and a self-administered anonymous questionnaire survey were conducted among 26 522 students recruited using multistage cluster sampling in 7 primary and secondary schools in 7 districts of Shanghai municipality from September to November 2021. An unconditional binary logistic regression model was used to analyze the association between piano playing and myopia prevalence among students. ResultsOf the students surveyed, 3 778 (14.2%) reported playing the piano. The myopia detection rate was 77.7% in students who reported playing the piano and significantly different from that 76.1% in those who did not (χ2 = 4.368, P < 0.05). After controlling for gender and parental myopia, no statistically significant association was found between piano playing and myopia prevalence. Compared to students who did not play piano and spent 2 hours or more per day in outdoor activities, students who did not play piano and spent less than 2 hours per day in outdoor activities had an increased risk of myopia (odds ratio [OR] = 1.153, 95% confidence interval [95%CI]: 1.073 – 1.239), and students who played piano and spent less than 2 hours per day in outdoor activities also had an increased risk of myopia (OR = 1.165, 95%CI: 1.038 – 1.308). Compared to the students who did not play piano and spent less than 2 hours per day studying outside the classroom, the students who did not play piano and spent 2 hours and more per day studying outside the classroom had an increased risk of myopia (OR = 1.212, 95%CI: 1.119 – 1.312) and the students who played piano and spent 2 hours and more per day studying outside the classroom also had an increased risk of myopia (OR = 1.203, 95%CI: 1.027 – 1.411). ConclusionThis study did not find a statistically significant association between piano playing and myopia prevalence in primary and secondary school students in Shanghai, and further prospective studies may investigate the association between piano playing and myopia in students.

Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro. In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

Microfluidic is a technology that allows the precise control of fluid in a micro-channel. With its advantages of high throughput and low cost, microfluidic technology has achieved good performance in various fields in recent years. Arthritis is a general term for a variety of joint diseases, which can be clinically manifested as joint pain and swelling, seriously affecting people's physical and mental health. At present, the causes of arthritis disease are still unknown, and existing disease models and treatment methods are still limited, so more treatments need to be developed. Microfluidic organ chip is a cutting-edge technology to build a bionic human organ model, which can reflect the structure and function characteristics of human organs by simulating the physiological environment of tissues and cells in vitro. This paper reviews the application of microfluidic technology in the modeling and treatment of arthritis, hoping to open up a new vision for the study of arthritis.

BackgroundThe treatment for papillary thyroid microcarcinoma (PTMC) is controversial. Central lymph node metastasis (CLNM) is one of the main predictors of recurrence and survival, accurate preoperative identification of CLNM is essential for surgical protocol establishment for PTMC. The objective of this study was to establish a nomogram to predict the possibility of CLNM in PTMC patients.MethodsA total of 3023 PTMC patients were randomly divided into two groups by a ratio of 7 to 3, the training group (n = 2116) and validation group (n = 907). The LASSO regression model and multivariate logistic regression analysis were performed to examine risk factors associated with CLNM. A nomogram for predicting CLNM was established and internally validated. Meanwhile, we follow-up the serum thyroid function FT3, FT4, TSH, Tg, TGAb and TPOAb in 789 PTMC patients for 4 years after surgery and compared the differences between the CLNM (+) and CLNM (-) groups, respectively.ResultsThe LASSO regression model and multivariate logistic regression analysis showed that younger age, lower BMI, being male, location in the lower pole, calcification, 1 ≥ diameter ≥ 0.5 cm, multifocality lesions, extra thyroidal extension (ETE), enlargement of central lymph node (ECLN), lateral lymph node metastasis (LLNM) and higher carcinoembryonic antigen were the ultimate risk factors for determining CLNM. A nomogram for predicting CLNM was constructed based on the influencing factors and internally validated. By establishing the prediction model, the AUC of CLNM in the training and validation groups were 0.73 (95% CI, 0.70-0.76) and 0.75 (95% CI, 0.71-0.79) respectively. Results of the DCA showed that the model is clinically useful when deciding on intervention in the most range of the threshold probability. A 4-year follow-up of thyroid function showed that FT3 and FT4 remained at stable levels after 3 months postoperative and were higher in the CLNM (+) group than in the CLNM (-) group. Hypothyroidism appeared predominantly within 3 months after surgery. The overall incidence of the CLNM (+) group and CLNM (-) groups were 16.46% and 12.04%, respectively.ConclusionThe nomogram model constructed in this study has a good predictive effect on CLNM in PTMC patients and provides a reasonable reference for clinical treatment.

Psoriasis is an immune system-mediated skin disease identified by the appearance of erythematous as a central symptom. As a recurrent and chronic inflammatory disease, psoriasis is influenced by both genetic and environmental factors and is known to be with no effective cure. Considering a multifaceted etiology of psoriasis, synergistic therapy exhibits great benefits over monotherapy, which becomes common for the treatment of various diseases. Herein, we present the nanozyme microspheres with structural color-coding labels for synergistic therapy of psoriasis. In particular, microsphere hydrogel is fabricated by the edible hydroxypropyl cellulose (HPC), which can generate a photonic liquid crystalline mesophase under lyotropic conditions in solution. Through adjustment of hydrogel components, microspheres endow with different functions, including moisturizing (paraffin), cfDNA scavenging (chitosan), and anti-inflammation (cerium oxide nanozyme). To improve patient convenience, hydrogel drops with different properties are tailored with different vivid structural colors by exploiting the lyotropic behavior of HPC. Of particular note, both in vitro and in vivo experiments have demonstrated the significant therapeutic effects of the encoded structural color microspheres. Green moisturizing microspheres facilitate to relieve dry, flaky skin patches; blue cfDNA scavenging and red anti-inflammatory microspheres significantly reduce skin inflammation. More importantly, combination therapy with encoded microspheres exerted the synergistic effects, including the increased body weight, thicker epidermal layer, and reduced immune activation. Overall, this synergistic treatment offers a promising platform for personalized management of psoriasis and various inflammatory skin diseases.

Abstract Background Senior nursing students’ perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students’ perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. Methods This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students’ Questionnaire and the Professional Identity Scale for Nursing Students. Results Three latent profiles were identified and labeled as “low perceived professional preparedness” (n = 90, 28.2%), “low clinical competency-low EBP (Evidence-Based Practice)” (n = 190, 59.5%), and “high perceived professional preparedness” (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p

Abstract Disulfidptosis, a newly discovered type of programmed cell death, could be a mechanism of cell death controlled by SLC7A11. This could be closely associated with tumor development and advancement. Nevertheless, the biological mechanism behind disulfidptosis-related genes (DRGs) in sarcoma (SARC) is uncertain. This study identified three valuable genes (SLC7A11, RPN1, GYS1) associated with disulfidptosis in sarcoma (SARC) and developed a prognostic model. The multiple databases and RT-qPCR data confirmed the upregulated expression of prognostic DRGs in SARC. The TCGA internal and ICGC external validation cohorts were utilized to validate the predictive model capacity. Our analysis of DRG riskscores revealed that the low-risk group exhibited a more favorable prognosis than the high-risk group. Furthermore, we observed a significant association between DRG riskscores and different clinical features, immune cell infiltration, immune therapeutic sensitivity, drug sensitivity, and RNA modification regulators. In addition, two external independent immunetherapy datasets and clinical tissue samples were collected, validating the value of the DRGs risk model in predicting immunotherapy response. Finally, the SLC7A11/hsa-miR-29c-3p/LINC00511, and RPN1/hsa-miR-143-3p/LINC00511 regulatory axes were constructed. This study provided DRG riskscore signatures to predict prognosis and response to immunotherapy in SARC, guiding personalized treatment decisions.

Abstract Background Numerous studies have shown that Schistosoma japonicum infection correlates with an increased risk of liver hepatocellular carcinoma (LIHC). However, data regarding the role of this infection in LIHC oncogenesis are scarce. This study aimed to investigate the potential mechanisms of hepatocarcinogenesis associated with Schistosoma japonicum infection. Methods By examining chronic liver disease as a mediator, we identified the genes contributing to Schistosoma japonicum infection and LIHC. We selected 15 key differentially expressed genes (DEGs) using weighted gene co-expression network analysis (WGCNA) and random survival forest models. Consensus clustering revealed two subgroups with distinct prognoses. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression identified six prognostic DEGs, forming an Schistosoma japonicum infection-associated signature for strong prognosis prediction. This signature, which is an independent LIHC risk factor, was significantly correlated with clinical variables. Four DEGs, including BMI1, were selected based on their protein expression levels in cancerous and normal tissues. We confirmed BMI1's role in LIHC using Schistosoma japonicum-infected mouse models and molecular experiments. Results We identified a series of DEGs that mediate schistosomiasis, the parasitic disease caused by Schistosoma japonicum infection, and hepatocarcinogenesis, and constructed a suitable prognostic model. We analyzed the mechanisms by which these DEGs regulate disease and present the differences in prognosis between the different genotypes. Finally, we verified our findings using molecular biology experiments. Conclusion Bioinformatics and molecular biology analyses confirmed a relationship between schistosomiasis and liver hepatocellular cancer. Furthermore, we validated the role of a potential oncoprotein factor that may be associated with infection and carcinogenesis. These findings enhance our understanding of Schistosoma japonicum infection's role in LIHC carcinogenesis.

Abstract Background Grasslands in drylands are increasingly influenced by human activities and climate change, leading to alterations in albedo and radiative energy balance among others. Surface biophysical properties and their interactions change greatly following disturbances. However, our understanding of these processes and their climatic impacts remains limited. In this study, we used multi-year observations from satellites and eddy-covariance towers to investigate the response of albedo to variables closely associated with human disturbances, including vegetation greenness (EVI) and surface soil volumetric water content (VWC), as well as snow cover and clearness index (T a) for their potential relationships. Results EVI and VWC during the growing season were the primary factors influencing albedo. EVI and VWC were negatively correlated with albedo, with VWC’s total direct and indirect impacts being slightly smaller than those of EVI. During the non-growing season, snow cover was the most influential factor on albedo. VWC and Ta negatively affected albedo throughout the year. We estimated the impact of variations in EVI and VWC on climate to be in the range of 0.004 to 0.113 kg CO2 m−2 yr−1 in CO2 equivalent. Conclusions This study indicates the significant impacts of climate change and human disturbances on vulnerable grassland ecosystems from the perspective of altered albedo. Changes in vegetation greenness and soil properties induced by climate change and human activities may have a substantial impact on albedo, which in turn feedback on climate change, indicating that future climate policies should take this factor into consideration.

Abstract Hepatocellular carcinoma (HCC) remains a formidable malignancy that significantly impacts human health, and the early diagnosis of HCC holds paramount importance. Therefore, it is imperative to develop an efficacious signature for the early diagnosis of HCC. In this study, we aimed to develop early HCC predictors (eHCC-pred) using machine learning-based methods and compare their performance with existing methods. The enhancements and advancements of eHCC-pred encompassed the following: (i) utilization of a substantial number of samples, including an increased representation of cirrhosis tissues without HCC (CwoHCC) samples for model training and augmented numbers of HCC and CwoHCC samples for model validation; (ii) incorporation of two feature selection methods, namely minimum redundancy maximum relevance and maximum relevance maximum distance, along with the inclusion of eight machine learning-based methods; (iii) improvement in the accuracy of early HCC identification, elevating it from 78.15 to 97% using identical independent datasets; and (iv) establishment of a user-friendly web server. The eHCC-pred is freely accessible at http://www.dulab.com.cn/eHCC-pred/ . Our approach, eHCC-pred, is anticipated to be robustly employed at the individual level for facilitating early HCC diagnosis in clinical practice, surpassing currently available state-of-the-art techniques.

Abstract Photon-initiated photoacoustic streaming (PIPS) with an Er: YAG laser has been introduced in root canal treatment to improve irrigation and facilitate the removal of bacteria in the root canal system. This study aimed to compare the antibacterial effectiveness of two different root canal irrigation techniques, conventional needle irrigation (CNI) and PIPS, using 1% sodium hypochlorite (NaOCl), in the treatment of teeth with apical periodontitis. Sixty patients with a total of sixty teeth affected by apical periodontitis were included in this study. The teeth underwent root canal therapy, and after mechanical instrumentation, they were randomly assigned to two groups (n = 30) based on the final irrigation protocol: CNI or PIPS with 1% NaOCl. Bacterial suspensions in the root canals were evaluated using Adenosine 5’-triphosphate (ATP) assay kit after mechanical instrumentation and after final irrigation. Then, a follow-up was conducted after 7 days. The results revealed that final irrigation significantly reduced ATP values in both the CNI and PIPS groups (P

The micro-patterned topography can affect bacterial enrichment and selective distribution by modifying the characteristics of material surface. In this study, we fabricated microcavity patterned silicon surfaces, and quantitatively explored the amount and distribution of Escherichia coli (E. coli) cells attached on a series of defined topographies. The results showed that E. coli cells enrichment was significantly increased on silicon nanowires-based microcavity array when compared to nanowires patterned silicon wafer. Furthermore, the microcavity diameter can control bacterial distribution by changing hydrophilic performance of interface. With the microcavity diameter of 7 µm, the cells colonized into the microcavity almost in its entirety, whilst distributed around the microcavity completely with 10 µm diameter, regardless of centre distances. This phenomenon can be explained by the Cassie-Baxter model equation according to the wettability. The distribution of bacterial enrichment changed with the silicon surfaces turning from non-wetting status to wetting status when treated with oxygen plasma to modify the hydrophobicity. These results demonstrated that microcavity patterned surface could favor bacterial enrichment on silicon and strictly confined bacterial distribution inside/outside the microcavity. Moreover, the nanowires inside microcavity can also increase electron conductivity and reduce the internal resistance, thus providing scientific evidence for the design of wearable microbial fuel cell with rational optimization and integration of different components for electronic skin.

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3β inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3β pathway.

Abstract With the innovation and evolution of lithium batteries, different active materials are loaded onto the current collectors, leading to remarkable changes in the components that directly interact with the current collectors. The surface/interface of current collectors in lithium batteries is gradually becoming one of the key factors to improve the overall performance. The thickness, material composition, surface morphology, and intrinsic properties of current collectors are crucial for understanding chemo‐mechanical changes during electrochemical reactions. Despite the widely acknowledged importance of highly efficient electron transportation and improved interfacial performance of current collectors as one of the determinants of exceptional lithium battery performance, insufficient attention has been given to exploring targeted design strategies for current collectors used in various lithium batteries. Particularly, as the development of solid‐state lithium batteries in full swing, there are limited studies focused on current collectors in all‐solid‐state lithium batteries (ASSLBs). This review introduces recent advancements in current collector technology, while highlighting both similarities and differences between negative current collectors applied in conventional lithium batteries and ASSLBs. Furthermore, we propose promising prospects for utilization of alloy materials as next‐generation negative current collectors.

Abstract Background A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices. Methods Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared. Results In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons’ performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p

Abstract Background Oxaliplatin resistance usually leads to therapeutic failure and poor prognosis in colorectal cancer (CRC), while the underlying mechanisms are not yet fully understood. Metabolic reprogramming is strongly linked to drug resistance, however, the role and mechanism of metabolic reprogramming in oxaliplatin resistance remain unclear. Here, we aim to explore the functions and mechanisms of purine metabolism on the oxaliplatin-induced apoptosis of CRC. Methods An oxaliplatin-resistant CRC cell line was generated, and untargeted metabolomics analysis was conducted. The inosine 5ʹ-monophosphate dehydrogenase type II (IMPDH2) expression in CRC cell lines was determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting analysis. The effects of IMPDH2 overexpression, knockdown and pharmacological inhibition on oxaliplatin resistance in CRC were assessed by flow cytometry analysis of cell apoptosis in vivo and in vitro. Results Metabolic analysis revealed that the levels of purine metabolites, especially guanosine monophosphate (GMP), were markedly elevated in oxaliplatin-resistant CRC cells. The accumulation of purine metabolites mainly arose from the upregulation of IMPDH2 expression. Gene set enrichment analysis (GSEA) indicated high IMPDH2 expression in CRC correlates with PURINE_METABOLISM and MULTIPLE-DRUG-RESISTANCE pathways. CRC cells with higher IMPDH2 expression were more resistant to oxaliplatin-induced apoptosis. Overexpression of IMPDH2 in CRC cells resulted in reduced cell death upon treatment with oxaliplatin, whereas knockdown of IMPDH2 led to increased sensitivity to oxaliplatin through influencing the activation of the Caspase 7/8/9 and PARP1 proteins on cell apoptosis. Targeted inhibition of IMPDH2 by mycophenolic acid (MPA) or mycophenolate mofetil (MMF) enhanced cell apoptosis in vitro and decreased in vivo tumour burden when combined with oxaliplatin treatment. Mechanistically, the Wnt/β-catenin signalling was hyperactivated in oxaliplatin-resistant CRC cells, and a reciprocal positive regulatory mechanism existed between Wnt/β-catenin and IMPDH2. Blocking the Wnt/β-catenin pathway could resensitize resistant cells to oxaliplatin, which could be restored by the addition of GMP. Conclusions IMPDH2 is a predictive biomarker and therapeutic target for oxaliplatin resistance in CRC.

Serratia marcescens is an opportunistic and nosocomial pathogen found in the intensive care unit (ICU), but its antimicrobial resistance (AMR) is rarely addressed. Here, we reported two blaKPC-2-positive S. marcescens strains, SMBC31 and SMBC50, recovered from the ICU of a hospital in Zhengzhou, China. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while S1-PFGE was employed to demonstrate plasmid size approximation. Complete genome sequences were obtained through Illumina NovaSeq 6000 and Oxford Nanopore Technologies. Both strains exhibit resistance to meropenem and harbor the blaKPC-2 and blaSRT-1 resistance genes. The plasmid pSMBC31-39K in strain SMBC31 and pSMBC50-107K in strain SMBC50 were identified as carrying the blaKPC-2 gene. Notably, both of these plasmids were successfully transferred to Escherichia coli strain J53. Phylogenetic analysis based on plasmid sequences revealed that pSMBC31-39K exhibited high homology with plasmids found in Aeromonas caviae, Citrobacter sp., and Pseudomonas aeruginosa, while pSMBC50-107K showed significant similarity to those of E. coli and Klebsiella pneumoniae. Notably, the coexistence of blaKPC-2 and blaSRT-1 was observed in all 94 KPC-2-producing S. marcescens strains by mining all genomes available under the GenBank database, which were mainly isolated from hospitalized patients. The emergence of multidrug-resistant S. marcescens poses significant challenges in treating clinical infections, highlighting the need for increased surveillance of this pathogen.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) and its emerging evolutionary branch toward hypervirulence have been neglected in pregnancy.MethodsFrom September 2020 to August 2021, an active surveillance culture program encompassed 138 randomly selected pregnant women, with five subjected to sample collection at two different time points. The clinical characterization was explored through statistical analysis. Whole-genome sequencing, a Galleria mellonella infection model, and a global database were used to investigate the genetic characterization, pathogenicity, evolutionary history, and phylogenetic relationships of the isolates.ResultsOf the 41 CRAB isolates obtained, they were divided into four ClustersRS and an orphan pattern. ClusterRS 1 (n = 31), with eight complex types in pregnancy, was also the dominant ClusterRS globally, followed by ClusterRS 13 (n = 5), identified as hypervirulent KL49 CRAB, exhibiting phylogeographical specificity to Guangdong. A maternal carriage CRAB rate of 26.09% (36/138) was revealed, with half of the isolates representing novel complex types, prominently including CT3071, as the first KL7 isolates identified in Shenzhen. Both KL49 and KL7 isolates were most commonly found in the same participant, suggesting potential intraspecific competition as a possible reason for CRAB infection without carriers during pregnancy. The independent risk factors for carriers were revealed for the first time, including advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection.ConclusionThe significant carriage rate and enhanced virulence of CRAB during pregnancy emphasize the imperative for routine surveillance to forestall dissemination within this high-risk group, especially in Guangdong for ClusterRS 13 isolates.

IntroductionPlastic pollution has surged due to increased human consumption and disposal of plastic products. Microbial communities capable of utilizing plastic as a carbon source may play a crucial role in degrading and consuming environmental plastic. In this study, we investigated the potential of a modified Winogradsky column (WC) to enrich Connecticut landfill soil for plastic-degrading bacteria and genes.MethodsBy filling WCs with landfill soil and inorganic Bushnell Haas medium, and incorporating polyethylene (PE) strips at different soil layers, we aimed to identify bacterial taxa capable of degrading PE. We employed high-throughput 16S rRNA sequencing to identify the microbes cultivated on the plastic strips and the intervening landfill soil. We used PICRUSt2 to estimate the functional attributes of each community from 16S rRNA sequences.Results and discussionAfter 12 months of incubation, distinct colors were observed along the WC layers, indicating successful cultivation. Sequencing revealed significant differences in bacterial communities between the plastic strips and the intervening landfill-soil habitats, including increased abundance of the phyla Verrucomicrobiota and Pseudomonadota (néé Proteobacteria) on the strips. Based on inferred genomic content, the most highly abundant proteins in PE strip communities tended to be associated with plastic degradation pathways. Phylogenetic analysis of 16S rRNA sequences showed novel unclassified phyla and genera enriched on the plastic strips. Our findings suggest PE-supplemented Winogradsky columns can enrich for plastic-degrading microbes, offering insights into bioremediation strategies.

Abstract Background The deep-sea snail Phymorhynchus buccinoides belongs to the genus Phymorhynchus (Neogastropoda: Raphitomidae), and it is a dominant specie in the cold seep habitat. As the environment of the cold seep is characterized by darkness, hypoxia and high concentrations of toxic substances such as hydrogen sulfide (H2S), exploration of the diverse fauna living around cold seeps will help to uncover the adaptive mechanisms to this unique habitat. In the present study, a chromosome-level genome of P. buccinoides was constructed and a series of genomic and transcriptomic analyses were conducted to explore its molecular adaptation mechanisms to the cold seep environments. Results The assembled genome size of the P. buccinoides was approximately 2.1 Gb, which is larger than most of the reported snail genomes, possibly due to the high proportion of repetitive elements. About 92.0% of the assembled base pairs of contigs were anchored to 34 pseudo‐chromosomes with a scaffold N50 size of 60.0 Mb. Compared with relative specie in the shallow water, the glutamate regulative and related genes were expanded in P. buccinoides, which contributes to the acclimation to hypoxia and coldness. Besides, the relatively high mRNA expression levels of the olfactory/chemosensory genes in osphradium indicate that P. buccinoides might have evolved a highly developed and sensitive olfactory organ for its orientation and predation. Moreover, the genome and transcriptome analyses demonstrate that P. buccinoides has evolved a sulfite-tolerance mechanism by performing H2S detoxification. Many genes involved in H2S detoxification were highly expressed in ctenidium and hepatopancreas, suggesting that these tissues might be critical for H2S detoxification and sulfite tolerance. Conclusions In summary, our report of this chromosome-level deep-sea snail genome provides a comprehensive genomic basis for the understanding of the adaptation strategy of P. buccinoides to the extreme environment at the deep-sea cold seeps.

Abstract Introduction The turnover and shortage of health care workers (HCWs) have been a worldwide problem for healthcare organizations. The primary aim of this study was to identify the factors influencing the intention of Chinese HCWs to leave their job, especially meaning in life and professional happiness. Methods This observational cross-sectional study, conducted among 1125 full-time HCWs, assessed demographic variables, meaning in life, professional happiness, and turnover intention by a survey. The survey was distributed to HCWs in three tertiary hospitals. The data were analyzed by T-tests, ANOVA, Kruskal–Wallis tests and hierarchical linear regression model. Results There were statistically significant differences in turnover intention of HCWs by gender, age, role, educational level, years in practice, and number of monthly night shifts. HCWs’ meaning in life and professional happiness were negatively associated with the turnover intention. Furthermore, after controlling for other factors, meaning in life explained 3.7% of the turnover intention and professional happiness explained 13.4%. Conclusion In our study, positive psychological factors were related to turnover intentions. Professional happiness was the strongest predictor. Thus, health human resource managers should foster positive psychology among HCWs to reduce their turnover.

Abstract Background Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. Methods We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. Results TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. Conclusions Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

The role of coastal mangrove wetlands in sequestering atmospheric carbon dioxide has been increasingly investigated in recent years. While studies have shown that mangroves are weak sources of methane (CH4) emissions, measurements of CH4 fluxes from these ecosystems remain scarce. In this study, we examined the temporal variation and biophysical drivers of ecosystem-scale CH4 fluxes in China’s northernmost mangrove ecosystem based on eddy covariance measurements obtained over a 3-year period. In this mangrove, the annual CH4 emissions ranged from 6.15 to 9.07 g C m−2 year−1. The daily CH4 flux reached a peak of over 0.07 g C m−2 day−1 during the summer, while the winter CH4 flux was negligible. Latent heat, soil temperature, photosynthetically active radiation, and tide water level were the primary factors controlling CH4 emissions. This study not only elucidates the mechanisms influencing CH4 emissions from mangroves, strengthening the understanding of these processes but also provides a valuable benchmark dataset to validate the model-derived carbon budget estimates for these ecosystems.

In this paper, a modified Josephson junction model is proposed, which splits the two-dimensional electron gas by inserting a middle superconductor strip into a conventional Josephson junction. This modification enhances the superconducting proximity effect, thus avoiding the appearance of a soft gap and inducing a stable Majorana zero-energy mode. Through numerical simulation, the impact of the middle superconductor strip with different widths on the energy band structure is studied, and a significant increase in the topological energy gap is found. In addition, the modified system maintains a robust topological gap even at a strong in-plane magnetic field.

Abstract Background Diaphorina citri Kuwayama is an important citrus pest. It serves as the vector for the transmission of Candidatus Liberibacter asiaticus (CLas), which induced a destructive disease, Huanglongbing, and caused huge economic losses. During the interaction between insects and plants, insects have evolved a series of mechanisms to adapt to various host plants. Murraya exotica and ‘Shatangju’ mandarin (Citrus reticulate cv. Shatangju) are the Rutaceae species from different genera that have been discovered as suitable hosts for D. citri adults. While the adaptation mechanism of this pest to these two host plants is unclear. Results In this study, RNA-seq and 16 S rDNA amplification sequencing were performed on the gut of D. citri adults reared on M. exotica and ‘Shatangju’ mandarin. RNA-seq results showed that a total of 964 differentially expressed genes were found in different gut groups with two host plant treatments. The impacted genes include those that encode ribosomal proteins, cathepsins, and mitochondrial respiratory chain complexes. According to 16 S rDNA sequencing, the compositions of the gut bacterial communities were altered by different treatments. The α and β diversity analyses confirmed that the host plant changes influenced the gut microbial diversity. The functional classification analysis by Tax4Fun revealed that 27 KEGG pathways, mostly those related to metabolism, including those for nucleotide metabolism, energy metabolism, metabolism of cofactors and vitamins, amino acid metabolism, carbohydrate metabolism, xenbiotics biodegradation and metabolism, lipid metabolism, and biosynthesis of other secondary metabolites, were significantly altered. Conclusion Our preliminary findings shed light on the connection between D. citri and host plants by showing that host plants alter the gene expression profiles and bacterial community composition of D. citri adults.

Improving economic resilience has become a regional development goal of policymakers. This study aims to investigate the effects of digital transformation on urban economic resilience and its underlying mechanisms. Based on a sample of 287 prefecture-level cities in China, We find that digital transformation helps improve urban economic resilience, which is robust to different estimations, e.g., 2SLS and staggered DID. Additionally, further analysis indicates that improving the efficiency and stimulating the level of innovation that is associated with digital transformation are likely to be the main mechanisms behind this effect. Our results reveal the following several policy implications. Firstly, formulating policies to develop digital technology and to promote its application is of great significance for achieving a sustainable and resilient economic growth in an increasingly uncertain environment. Secondly, the government should focus on promoting market-oriented reform, reducing government intervention, protecting intellectual property rights, and creating an innovative environment to maximize the effect of digital technology. Thirdly, during the normal periods, accelerating the digitalization process will promote the balanced development among urbans.

Trabeculectomy is the primary surgical approach used to treat glaucoma, but scarring of the filtering passage (filtering bleb) after surgery often leads to treatment failure. To address this issue, we have developed a drug release system called RSG/Pd@ZIF-8 PHBV film. This system enables the sustained release of an anti-fibrosis drug, aiming to prevent scarring. In vitro, the film has the function of continuous Rosiglitazone (RSG) release, with accelerated release after laser irradiation. The antibacterial experiments revealed that the film exhibited antibacterial rates of 87.0 % against E.coli and 97.1 % against S.aureus, respectively. Moreover, we confirmed its efficacy in a rabbit eye model undergoing trabeculectomy. After implantation of the film, we observed a prolonged postoperative period for reducing intraocular pressure (IOP), increased survival rate of filtering blebs, and improved long-term surgical outcomes in vivo. Additionally, the film exhibited excellent biosafety. In summary, the designed sustained-release film in this study possesses the aforementioned functionalities, allowing for the regulation of anti-scarring drug release without causing harm post-surgery. This personalized and precise anti-scarring strategy represents a significant advancement.

Background and Objective. Oral submucous fibrosis (OSF) is a progressive and irreversible disorder of collagen metabolism, resulting in mucosal fibrosis, oral functional changes, and even malignant transformation. This study investigated the relationship between human leukocyte antigen (HLA)-DQB1 alleles and the susceptibility to OSF in a Hunan Han population, providing a new basis for clinical prevention and treatment of OSF. Methods. 44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. Results. The expression frequency of the HLA-DQB1 ∗05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1 ∗05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald χ2 = 5.681, P=0.017). However, there were no significant differences in the allele expression frequencies of DQB1 ∗02 : 01, DQB1 ∗03 : 03, DQB1 ∗05 : 01, DQB1 ∗05 : 03, DQB1 ∗06 : 02, DQB1 ∗06 : 03, and DQB1 ∗06 : 04 in the OSF group compared with the controls (all P>0.05). Furthermore, the relative expression level of the HLA-DQB1 ∗05 : 02 allele in the OSF group (3.98 ± 3.50) was significantly higher than in controls (0.70 ± 0.41). Conclusions. There are differences in the HLA-DQB1 allele polymorphisms between the healthy population and patients with oral submucosal fibrosis. Preliminarily, it is suggested that the HLA-DQB1 ∗05 : 02 allele, which has a strong correlation with OSF and great differential expression between patients with OSF and controls, might be a susceptibility gene for OSF in Hunan.

Objective: The epidemiological information associated with seizure-related burn injuries is lacking in China. Therefore, this study aims to analyze the clinical profile, management, outcome, and risk factors of burns that are directly caused by seizures among epileptic patients, and identify the epidemiological characteristics to develop effective preventive strategies. Methods: This study was conducted between January 2002 and December 2022 in a large Chinese burn center. Data including clinical profile, wound treatment, and outcome were analyzed. A multiple linear regression was used to screen the risk factors for the length of hospital stay (LOS), and a multiple logistic regression was used to screen the contributory factors for the amputation. Results: A total of 184 burn patients (55.98 % females) were enrolled, with a 0.78 % incidence rate during the study period. The mean age of the patients was 36.16 years (SD: 17.93). Patients aged 20–29 were the most affected age groups (23.37 %). Most burns were caused by flame, accounting for 60.33 % (111/184) of all cases. In total, 76.09 % of the 184 patients underwent at least one operation, and 35 patients (19.02 %) still required amputation during the study period. Burn sites (hands) had the greatest impact on amputation (OR = 3.799), followed by flame burns (OR = 3.723). The mean LOS/TBSA was 6.90 ± 8.53 d, and a larger TBSA, full-thickness burns, and a higher number of operations were identified as the risk factors for a longer LOS. There was one death among the 184 patients, with a mortality rate of 0.54 %. Conclusion: This study demonstrates that burn injuries are extremely harmful to individuals with epilepsy in China because they are at high risk of amputation and disability. Effective healthcare education and preventive programs that focus on lifestyle modifications and seizure control should be implemented to reduce the burn incidence in these populations.

Edible chrysanthemum is a common food resource for tea and functional foods with potential benefits for human health. Studies have indicated that chrysanthemum has the potential effect on inflammatory diseases, while the effects on gouty inflammation remain underexplored. The present study aimed to investigate the anti-gout activity and characterize the active ingredients of chrysanthemums by using metabolite profiles, in vitro experiments, and spectrum-effect analysis. Results showed that ‘Boju’ (BJ), ‘Hangbaiju’ (HBJ), and ‘Huaiju’ (HJ) exhibited regulatory effects on monosodium urate (MSU)-induced inflammation. At the dose of 50 µg/mL, the inhibitory rates of IL-1β secretion were 24.53 %, 14.36 %, and 38.10 %, respectively. A total of 32 phenolic compounds were identified or preliminarily assigned in UPLC-Q/TOF-MS analysis. And seven phenolics related to anti-gout activity were identified by spectrum-effect relationships. According to ADME (absorption, distribution, metabolism, excretion) evaluation and experiments verification, luteolin, acacetin-7-O-glucoside, and apigenin-7-O-glucoside were critical constituents potentially associated with the reduction of inflammation in gout. Additionally, these phenolics might be suitable as quality control indicators. This study clarified the anti-gout properties of different cultivars of chrysanthemums and active compounds, providing a theoretical basis for its scientific utilization in functional foods.

Abstract Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.

COVID-19, caused by SARS-CoV-2, has emerged as the most destructive emerging infectious disease of the 21st century. Vaccination is an effective method to combat viral diseases. However, due to the constant mutation of the virus, new variants may weaken the efficacy of vaccines. In the current field of new coronavirus research, viral protease inhibitors have emerged as a highly regarded therapeutic strategy. Nevertheless, existing viral protease inhibitors do not fully meet the therapeutic needs. Therefore, this paper turned to traditional Chinese medicine to explore new active compounds. This study focused on 24 isolated compounds from Acorus calamus L. and identified 8 active components that exhibited significant inhibitory effects on SARS-CoV-2 PLpro. Among these, the compound 1R,5R,7S-guaiane-4R,10R-diol-6-one demonstrated the best inhibitory activity with IC50 values of 0.386 ± 0.118 μM. Additionally, menecubebane B and neo-acorane A exhibited inhibitory activity against both Mpro and PLpro proteases, indicating their potential as dual-target inhibitors. The molecular docking results confirmed the stable conformations of these compounds with the key targets and their good activity. ADMET and Lipinski’s rule analyses revealed that all the small molecule ligands possessed excellent oral absorption properties. This study provides an experimental foundation for the discovery of promising antiviral lead compounds.

Clarifying the ecosystem service (ES) trade-off/synergy is a prerequisite for scientific implementation and optimization of integrated ecological system management strategies, especially in highly urbanized areas with declining eco-environmental carrying capacity. This study took China's Yangtze River Delta urban agglomeration (YRDUA) as an example. First, we used a pixel-by-pixel analysis based on dynamic spatial correlation to quantify the trade-off/synergy among the 6 primary ESs' change amounts from 2005 to 2020 (habitat quality, soil retention, carbon sequestration, water yield, food production, leisure and recreation). Then, we integrated the multiple ES trade-off/synergy and explored their driving factors by spatial cluster analysis and geographically and temporally weighted regression (GTWR). The results showed synergy between supporting and regulating services predominated while regulating services were mostly trade-offs with regulating and cultural services. The trade-off/synergy of the 15 ES functional pairs within YRDUA can be downscaled into 4 ES trade-off and synergy bundles. Furthermore, the climate drivers (annual highest temperature (TH), annual total precipitation (PRE), annual total solar radiation (SRT)) significantly influenced the spatial heterogeneity of the 6 ESs in the YRDUA. The socio-economic drivers (night light index (NLI), gross domestic product (GDP)) and land use drivers (proportion of arable land (ALP), proportion of construction land (CLP), proportion of woodland (WLP)) had a more remarkable power of explanation for the ES temporal variation and ES trade-off/synergy. YRDUA and other urban agglomerations can use the study's findings to develop differentiated integrated ecological management strategies.

Engaging the public in low-carbon community development is an important step toward achieving the UN Sustainability Goals. Research on residents' participation in low-carbon activities has primarily focused on socio-demographic, economic, and institutional contextual factors. How residents' subjective perceptions of place influence their participation in developing low-carbon communities has scarcely been studied. This study examines the relationship between place attachment and public attitudes and behaviors towards low-carbon community development in Beijing, China. A three-dimensional model of place attachment including personal, social, and environmental contexts was proposed. Exploratory factor analysis, confirmative factor analysis and structural equation modeling were conducted via a survey of 300 participants. Results confirm the validity of the three-dimensional model of place attachment and indicate (a) a significant and positive effect of place attachment on participation attitude; (b) a significant and positive effect of place attachment on participation behavior; (c) a significant and positive effect of participation attitude on behavior; and (d) environmental contexts more strongly affect participation attitude and behavior than personal and social contexts. The findings assist relevant authorities in engaging locals in low-carbon participation by investing in neighborhood revitalisation, promoting social outreach activities and sharing low-carbon knowledge. Practitioners should consider both symbolic and environmental elements for residents when planning and renewing communities.

Sulfide-based all-solid-state batteries (ASSBs) exhibit unparalleled application value due to the high ionic conductivity and good processability of sulfide solid electrolytes (SSEs). Carbon-based conductive agents (CAs) are often used in the construction of electronic conductive networks to achieve rapid electron transfer. However, CAs accelerate the formation of decomposition products of SSEs, and their effects on sulfide-based ASSBs are not fully understood. Herein, the effect of CAs (super P, vaper-grown carbon fibers, and carbon nanotubes) on the performance of sulfide-based ASSBs is investigated under different cathode active materials mass loading (8 and 25 ​mg·cm−2). The results show that under low mass loading, the side reaction between the CAs and the SSEs deteriorates the performance of the cell, while the charge transfer promotion caused by the addition of CAs is only manifested under high mass loading. Furthermore, the gradient design strategy (enrichment of CAs near the current collector side and depletion of CAs near the electrolyte side) is applied to maximize the benefits of CAs in electron transport and reduce the adverse effects of CAs. The charge carrier transport barrier inside the high mass loading electrode is significantly reduced through the regulation of electronic conductivity. Consequently, the optimized electrode achieves a high areal capacity of 5.6 ​mAh·cm−2 at high current density (1.25 ​mA·cm−2, 0.2 ​C) at 25 °C with a capacity retention of 87.85% after 100 cycles. This work provides a promising way for the design of high-mass loading electrodes with practical application value.

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 ( P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 ( P = .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference ( P = .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 ( P = .013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

Abstract The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.

Pomacea canaliculata is a malignant invasive aquatic snail found worldwide, and niclosamide (NS) is one of the primary agents used for its control. NS applied to water will exist in non-lethal concentrations for some time due to degradation or water exchange, thus resulting in sublethal effects on environmental organisms. To identify sublethal effects of NS on Pomacea canaliculata, we studied the aspects of histopathology, oxygen-nitrogen ratio (RO∶N), enzyme activity determination, and gene expression. After LC30 NS treatment (0.310 g/L), many muscle fibers of the feet degenerated and some acinar vesicles of the hepatopancreas collapsed and dissolved. The oxygen-nitrogen ratio (RO∶N) decreased significantly from 15.0494 to 11.5183, indicating that NS had changed the metabolic mode of Pomacea canaliculata and shifted it primarily to protein catabolism. Transcriptome analysis identified the sublethal effects of LC30 NS on the snails at the transcriptional level. 386, 322, and 583 differentially expressed genes (DEGs) were identified in the hepatopancreas, gills, and feet, respectively. GO (Gene Ontology) functional analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotations showed that DEGs in the hepatopancreas were mainly enriched for sugar metabolism, protein biosynthesis, immune response, and amino acid metabolism functional categories; DEGs in the gills were mainly enriched for ion transport and amino acid metabolism; DEGs in the feet were mainly enriched for transmembrane transport and inositol biosynthesis. In the future, we will perform functional validation of key genes to further explain the molecular mechanism of sublethal effects.

ABSTRACT The aim of this study was to investigate the transferability of acquired linezolid resistance genes and associated mobile genetic elements in an Enterococcus faecalis isolate QZ076, cocarrying optrA, cfr, cfr(D), and poxtA2 genes. MICs were determined by broth microdilution. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The transfer of linezolid resistance genes was investigated by conjugation, using E. faecalis JH2-2 and clinical methicillin-resistant Staphylococcus aureus (MRSA) 109 as recipients. E. faecalis QZ076 harbors four plasmids, designated pQZ076-1 to pQZ076-4, with optrA located in the chromosomal DNA. The gene cfr was located on a novel pseudocompound transposon, designated Tn7515, integrated into the 65,961-bp pCF10-like pheromone-responsive conjugative plasmid pQZ076-1. Tn7515 generated 8-bp direct target duplications (5′-GATACGTA-3′). The genes cfr(D) and poxtA2 were colocated on the 16,397-bp mobilizable broad-host-range Inc18 plasmid pQZ076-4. The cfr-carrying plasmid pQZ076-1 could transfer from E. faecalis QZ076 to E. faecalis JH2-2, along with the cfr(D)- and poxtA2-cocarrying plasmid pQZ076-4, conferring the corresponding resistant phenotype to the recipient. Moreover, pQZ076-4 could also transfer to MRSA 109. To the best of our knowledge, this study presented the first report of four acquired linezolid resistance genes [optrA, cfr, cfr(D), and poxtA2] being simultaneously present in the same E. faecalis isolate. The location of the cfr gene on a pseudocompound transposon in a pheromone-responsive conjugative plasmid will accelerate its rapid dissemination. In addition, the cfr-carrying pheromone-responsive conjugative plasmid in E. faecalis was also able to mobilize the interspecies transfer of the cfr(D)- and poxtA2-cocarrying plasmid between enterococci and staphylococci. IMPORTANCE In this study, the simultaneous occurrence of four acquired oxazolidinone resistance genes [optrA, cfr, cfr(D), and poxtA2] was identified in an E. faecalis isolate of chicken origin. The association of the cfr gene with a novel pseudocompound transposon Tn7515 integrated into a pCF10-like pheromone-responsive conjugative plasmid will accelerate its dissemination. Moreover, the location of the resistance genes cfr(D) and poxtA2 on a mobilizable broad-host-range Inc18 family plasmid represents the basis for their intra- and interspecies dissemination with the aid of a conjugative plasmid and further accelerates the spreading of acquired oxazolidinone resistance genes, such as cfr, cfr(D), and poxtA2, among Gram-positive pathogens.

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H2O2 stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of HCC has been associated with a disorder in bile acid (BA) metabolism. In this study, we employed an integrative approach, combining various datasets and omics analyses, to comprehensively characterize the tumor microenvironment in HCC based on genes related to BA metabolism. Our analysis resulted in the classification of HCC samples into four subtypes (C1, C2a, C2b, and C3). Notably, subtype C2a, characterized by the highest bile acid metabolism score (BAMS), exhibited the highest survival probability. This subtype also demonstrated increased immune cell infiltration, lower cell cycle scores, reduced AFP levels, and a lower risk of metastasis compared to subtypes C1 and C3. Subtype C1 displayed poorer survival probability and elevated cell cycle scores. Importantly, the identified subtypes based on BAMS showed potential relevance to the gene expression of drug targets in currently approved drugs and those under clinical research. Genes encoding VEGFR (FLT4 and KDR) and MET were elevated in C2, while genes such as TGFBR1, TGFB1, ADORA3, SRC, BRAF, RET, FLT3, KIT, PDGFRA, and PDGFRB were elevated in C1. Additionally, FGFR2 and FGFR3, along with immune target genes including PDCD1 and CTLA4, were higher in C3. This suggests that subtypes C1, C2, and C3 might represent distinct potential candidates for TGFB1 inhibitors, VEGFR inhibitors, and immune checkpoint blockade treatments, respectively. Significantly, both bulk and single-cell transcriptome analyses unveiled a negative correlation between BA metabolism and cell cycle-related pathways. In vitro experiments further confirmed that the treatment of HCC cell lines with BA receptor agonist ursodeoxycholic acid led to the downregulation of the expression of cell cycle-related genes. Our findings suggest a plausible involvement of BA metabolism in liver carcinogenesis, potentially mediated through the regulation of tumor cell cycles and the immune microenvironment. This preliminary understanding lays the groundwork for future investigations to validate and elucidate the specific mechanisms underlying this potential association. Furthermore, this study provides a novel foundation for future precise molecular typing and the design of systemic clinical trials for HCC therapy.

Postoperative cognitive dysfunction (POCD) is associated with increased postoperative morbidity and mortality in patients. Excessive production of reactive oxygen species (ROS) and the consequent inflammatory response in the postoperative brain play crucial roles in the development of POCD. However, effective ways to prevent POCD have yet to be developed. Moreover, effective penetration of the blood-brain barrier (BBB) and maintaining viability in vivo are major challenges for preventing POCD using traditional ROS scavengers. Herein, mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized by co-precipitation method. The BBB penetration of mSPIONs was verified through fluorescent imaging and ICP-MS quantification. The ROS scavenging and anti-inflammatory of mSPIONs were evaluated in H2O2-treated J774A.1 ​cells and in tibial fracture mice model. The novel object recognition (NOR) and trace-fear conditioning (TFC) were used to test the cognitive function of postoperative mice. The average diameter of mSPIONs was approximately 11 ​nm. mSPIONs significantly reduced ROS levels in H2O2-treated cells and in hippocampus of surgical mice. mSPIONs administration reduced the levels of IL-1β and TNF-α in the hippocampus and inhibited surgery-upregulated HIF1-α/NF-κB signaling pathway. Moreover, mSPIONs significantly improved the cognitive function of postoperative mice. This study provides a new approach for preventing POCD using a nanozyme.

The tigecycline resistance gene tet(X4) was widespread in various bacteria. However, limited information about the plasmid harboring the tet(X4) gene spread among the different species is available. Here, we investigated the transmission mechanisms of the tet(X4) gene spread among bacteria in a pig farm. The tet(X4) positive Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Enterobacter hormaeche were identified in the same farm. The whole genome sequencing (WGS) analysis showed that the K. pneumoniae belonged to ST727 (n = 11) and ST3830 (n = 1), E. cloacae and E. hormaeche belonged to ST524 (n = 1) and ST1862 (n = 1). All tet(X4) genes were located on the IncHI1 plasmids that could be conjugatively transferred into the recipient E. coli C600 at 30°C. Moreover, a fusion plasmid was identified that the IncHI1 plasmid recombined with the IncN plasmid mediated by ISCR2 during the conjugation from strains B12L to C600 (pB12L-EC-1). The fusion plasmid also has been discovered in a K. pneumoniae (K1L) that could provide more opportunities to spread antimicrobial resistance genes. The tet(X4) plasmids in these bacteria are derived from the same plasmid with a similar structure. Moreover, all the IncHI1 plasmids harboring the tet(X4) gene in GenBank belonged to the pST17, the newly defined pMLST. The antimicrobial susceptibility testing was performed by broth microdilution method showing the transconjugants acquired the most antimicrobial resistance from the donor strains. Taken together, this report provides evidence that IncHI1/pST17 is an important carrier for the tet(X4) spread in Enterobacteriaceae species, and these transmission mechanisms may perform in the environment.

ABSTRACT: Objectives: This study aimed to identify tigecycline-resistant tet(X4)-bearing Escherichia fergusonii isolated from pigs in China with a complete genome sequence. Methods: E. fergusonii was isolated by selective medium and screened from tigecycline-supplemented agar plates. The microbroth dilution method was used for antimicrobial susceptibility testing, and the minimal inhibitory concentration (MIC) results refer to the interpretation standard in the Clinical and Laboratory Standards Institute of America (CLSI). Whole-genome sequencing was performed on the Illumina HiSeq and Nanopore GridION platforms. The antimicrobial resistance (AMR) genes virulence genes and replicon types of plasmids were predicted by the CGE server. Results: E. fergusonii EF21QZZ116 was identified from 760 faecal and caecal content samples and was resistant to tigecycline, tetracycline, ampicillin, sulfisoxazole, trimethoprim-sulfamethoxazole, spectinomycin, and florfenicol. The AMR genes tet(X4), blaTEM-1B, and floR are located on the hybrid IncFIA-IncHI1A-IncHI1B plasmid pQZZ166-tetX-190K and are 190 391 bp in length. This hybrid plasmid has high homology with the plasmids of Escherichia coli, Enterobacter cloacae, Klebsiella, Citrobacter, and Salmonella based on comparison and analysis with the NCBI database. Notably, conjugative transfer and S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) assays show that the plasmid can transfer horizontally. Conclusion: To the best of our knowledge, this is the first report of E. fergusonii carrying the tet(X4) gene isolated from a pig; this report provides insight into the AMR characteristics of E. fergusonii and offers insight into public health.

Abstract Purpose Parkinson's disease (PD) is the second most common neurodegenerative disease without cure or effective treatment. This study explores whether the yeast internal NADH-quinone oxidoreductase (NDI1) can functionally replace the defective mammalian mitochondrial complex I, which may provide a gene therapy strategy for treating sporadic PD caused by mitochondrial complex I dysfunction. Method Recombinant lentivirus expressing NDI1 was transduced into SH-SY5Y cells, or recombinant adeno-associated virus type 5 expressing NDI1 was transduced into the right substantia nigra pars compacta (SNpc) of mouse. PD cell and mouse models were established by rotenone treatment. The therapeutic effects of NDI1 on rotenone-induced PD models in vitro and vivo were assessed in neurobehavior, neuropathology, and mitochondrial functions, by using the apomorphine-induced rotation test, immunohistochemistry, immunofluorescence, western blot, complex I enzyme activity determination, oxygen consumption detection, ATP content determination and ROS measurement. Results NDI1 was expressed and localized in mitochondria in SH-SY5Y cells. NDI1 resisted rotenone-induced changes in cell morphology, loss of cell viability, accumulation of α-synuclein and pS129 α-synuclein, mitochondrial ROS production and mitochondria-mediated apoptosis. The basal and maximal oxygen consumption, mitochondrial coupling efficiency, basal and oligomycin-sensitive ATP and complex I activity in cell model were significantly increased in rotenone + NDI1 group compared to rotenone + vector group. NDI1 was efficiently expressed in dopaminergic neurons in the right SNpc without obvious adverse effects. The rotation number to the right side (NDI1-treated side) was significantly increased compared to that to the left side (untreated side) in mouse model. The number of viable dopaminergic neurons, the expression of tyrosine hydroxylase, total and maximal oxygen consumption, mitochondrial coupling efficiency and complex I enzyme activity in right substantia nigra, and the content of dopamine in right striatum were significantly increased in rotenone + NDI1 group compared to rotenone + vector group. Conclusion Yeast NDI1 can rescue the defect of oxidative phosphorylation in rotenone-induced PD cell and mouse models, and ameliorate neurobehavioral and neuropathological damages. The results may provide a basis for the yeast NDI1 gene therapy of sporadic PD caused by mitochondrial complex I dysfunction.

Four crisping diets were designed to conduct a feeding experiment to investigate the use of broad bean in the formulated feed of Nile tilapia and optimize its use. The growth performance, muscle characteristics, antioxidant capacity, and intestinal health of Nile tilapia with an initial body weight of 617.32 ± 1.64 g were evaluated after being fed with different diets for 90 days. The results showed no adverse effect on the growth performance of Nile tilapia fed with broad bean diets. Contrastingly, some improvements were found in WGR and SGR, but a lower FCR was obtained. The supplementation of broad beans weakened the antioxidant capacity of fish but did not influence liver health and the immune system. Increasing the amount of broad bean addition can increase muscle quality values, and an embrittling functional package being added to the diet can also improve muscle hardness, adhesiveness, and chewiness of Nile tilapia muscle. In addition, the crisping functional package can be applied to tilapia crisping formulated feed, which helps to improve the integrity of the intestinal tissue structure and optimize the intestinal microbiota of Nile tilapia. The final achievement of this study is to provide a theoretical reference for optimizing the breeding technology of crispy Nile tilapia and developing a specialized crisping diet for the species.