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Abstract Background Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. Methods A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. Results H. pylori can colonize the host’s stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. Conclusions H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process. Graphical abstract

Abstract Background Mobility limitations (e.g., using wheelchair) have been closely linked to diminished functional independence and quality of life in older adults. The regulation of mobility is pertaining to multiple neurophysiologic and sociodemographic factors. We here aimed to characterize the relationships of these factors to the risk of restricted mobility in older adults. Methods In this longitudinal study, 668 older adults with intact mobility at baseline completed the baseline assessments of clinical characteristics, cognitive function, sleep quality, activities of daily living (ADL), walking performance, beat-to-beat blood pressure, and structural MRI of the brain. Then 506 of them (mean age = 70.7 ± 7.5 years) responded to the follow-up interview on the mobility limitation (as defined by if using wheelchair, cane, or walkers, or being disabled and lying on the bed) after 18 ± 3.5 months. Logistic regression analyses were performed to examine the relationships between the baseline characteristics and the follow-up mobility restriction. Results At baseline, compared to intact-mobility group (n = 475), restricted-mobility group (n = 31) were older, with lower score of ADL and the Montreal Cognitive Assessment (MoCA), greater score of Pittsburgh Sleep Quality Index (PSQI), poorer cardio- and cerebral vascular function, and slower walking speeds (ps

Abstract. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

Abstract Western criminological literature continues to focus on the binary control system (formal vs. informal), while China has long employed the trinary system (formal, semiformal, and informal) in its construction of social control. China scholars have investigated the prevalence and importance of the trinary control system as a key to understanding social control. However, there is a lack of research on their predictors. The current study aims at investigating the correlates of the prevalence and importance of the observed trinary control system in rural China. Using the sample data of 2343 respondents collected from 164 villages in rural China, the study found that both individual and village factors were the predictors of the prevalence of the observed controls exerted by village committees, a measure of semiformal control, and police, a measure of formal control, in maintaining community social order. Findings included the reported prevalence of four control mechanisms as significant predictors of their importance in community order maintenance. The implications of these findings are discussed.

Abstract The harmonic compensation of SAPF (shunt active power filter) may trigger harmonic oscillation due to the interaction with grid impedance and non‐linear loads, which distorts the power quality. In previous research, the relevant mechanism has been studied. However, the SAPF generally employs complex harmonic detection algorithm, which significantly increases the computational demands. The SAPF in full compensation mode can effectively solve this problem. But the modification of harmonic detection link may change the oscillation mechanism and previous stabilization methods need to be re‐evaluated. Therefore, this paper establishes the small signal model of the SAPF system in full compensation mode and investigates its oscillation mechanism. It is revealed that harmonic compensation and passive resonance collectively induce the harmonic oscillation. Based on the model, the working mechanism and application performance of the main stabilization methods proposed in the past (harmonic virtual admittance and harmonic compensation canceling) are analyzed and compared. However, neither of them can achieve effective stabilization without sacrificing the performance of compensation. Consequently, the harmonic phase compensation method is proposed to achieve the stabilization of the SAPF system in full compensation mode without affecting normal compensation. Finally, simulations and experiments are performed to verify the mechanism analysis and proposed methods.

The application of machine learning techniques in biological research, especially when dealing with limited data availability, poses significant challenges. In this study, we leveraged advancements in method development for predicting protein-protein binding strength to conduct a systematic investigation into the application of machine learning on limited data. The binding strength, quantitatively measured as binding affinity, is vital for understanding the processes of recognition, association, and dysfunction that occur within protein complexes. By incorporating transfer learning, integrating domain knowledge, and employing both deep learning and traditional machine learning algorithms, we mitigated the impact of data limitations and made significant advancements in predicting protein-protein binding affinity. In particular, we developed over 20 models, ultimately selecting three representative best-performing ones that belong to distinct categories. The first model is structure-based, consisting of a random forest regression and thirteen handcrafted features. The second model is sequence-based, employing an architecture that combines transferred embedding features with a multilayer perceptron. Finally, we created an ensemble model by averaging the predictions of the two aforementioned models. The comparison with other predictors on three independent datasets confirms the significant improvements achieved by our models in predicting protein-protein binding affinity. The programs for running these three models are available at https://github.com/minghuilab/BindPPI.

Heterostructured design and microcrack management mitigate the strength-ductility dilemma in metallic materials. Here, we demonstrate a simultaneous enhancement of strength and ductility in graphene-decorated bimodal pure nickel, achieving a strength increase to 1 GPa and an 18% improvement in elongation by designing heterostructure with graphene, metal powders, and metal foams. The results show that grain refinement, hetero-deformation-induced hardening, and activated stacking faults mainly cause the strength-ductility synergy. Additionally, while dispersed microcracks nucleate within the fine grain zones, their propagation is constrained by the coarse grain zones. This study provides new insights into improving the strength-ductility combination in metallic materials.

This paper introduced a novel semiring structure involving nonnegative integers, where operations depended on the comparison of the magnitudes of decimal digit sums. Consequently, a corresponding matrix semiring can be established on this commutative semiring. We showed that the 3-satisfiability problem can be polynomial-time reduced to solving systems of quadratic polynomial equations over this semiring. We proposed a key exchange protocol based on this matrix semiring, with its security relying on the two-sided digital circulant matrix action problem over this semiring. This scheme provides a novel cryptographic primitive for post-quantum cryptography.

Abstract 5-Fluorouracil (5-FU) is the primary treatment option for advanced gastric cancer. However, the current challenge lies in the absence of validated biomarkers to accurately predict the efficacy and sensitivity of 5-FU in individual patients. It has been confirmed that 5-FU can regulate tumor progression by promoting gasdermin E (GSDME, encoded by DFNA5) cleavage to induce pyroptosis. Lysine demethylase ALKBH4 has been shown to be upregulated in a variety of tumors to promote tumor progression. However, its role in gastric cancer is not clear. In this study, we observed a significant upregulation of ALKBH4 expression in gastric cancer tissues compared to adjacent normal tissues, indicating its potential as a predictor for the poor prognosis of gastric cancer patients. On the contrary, GSDME exhibits low expression levels in gastric cancer and demonstrates a negative correlation with poor prognosis among patients diagnosed with gastric cancer. In addition, we also found that high expression of ALKBH4 can inhibit pyroptosis and promote the proliferation of gastric cancer cells. Mechanistically, ALKBH4 inhibits GSDME activation at the transcriptional level by inhibiting H3K4me3 histone modification in the GSDME promoter region, thereby reducing the sensitivity of gastric cancer cells to 5-FU treatment. These findings provide further insight into the regulatory mechanisms of ALKBH4 in the progression of gastric cancer and underscore its potential as a prognostic marker for predicting the sensitivity of gastric cancer cells to 5-FU treatment.

Abstract. Background:. Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model. Methods:. Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results:. HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P

Soil metabolomics is an emerging approach for profiling diverse small molecule metabolites, i.e., metabolomes, in the soil. Soil metabolites, including fatty acids, amino acids, lipids, organic acids, sugars, and volatile organic compounds, often contain essential nutrients such as nitrogen, phosphorus, and sulfur and are directly linked to soil biogeochemical cycles driven by soil microorganisms. This paper presents an overview of methods for analyzing soil metabolites and the state-of-the-art of soil metabolomics in relation to soil nutrient cycling. We describe important applications of metabolomics in studying soil carbon cycling and sequestration, and the response of soil organic pools to changing environmental conditions. This includes using metabolomics to provide new insights into the close relationships between soil microbiome and metabolome, as well as responses of soil metabolome to plant and environmental stresses such as soil contamination. We also highlight the advantage of using soil metabolomics to study the biogeochemical cycles of elements and suggest that future research needs to better understand factors driving soil function and health.

Abstract The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2 −/− mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2 −/− BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-β1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Evaluating the water resources spatial equilibrium (WRSE) is the foundation for scientifically planning the construction of an optimized water resource allocation system and achieving the high-standard development of the China Water Network Project. To elucidate the characteristics of WRSE variation in Ulanqab City, this study explored a novel WRSE assessment model based on connection number and the subtraction set pair potential method. The results indicate that: (1) there exists a mismatch between the distribution of water resources in Ulanqab City and its socio-economic development. In 2020, the Gini coefficients of water resources total quantity concerning resident population, gross domestic product (GDP), industrial output value, and irrigated land area were 0.48, 0.48, 0.51, and 0.28, respectively. (2) From 2011 to 2020, the overall WRSE level in Ulanqab City showed an increasing trend year by year. Among them, the WRSE levels in six counties improved, while Jining District consistently remained at a low equilibrium state due to the prominent contradiction between water supply and demand. (3) In the future, Ulanqab City can further enhance the WRSE level by promoting the reuse of recycled water, intensifying groundwater pollution control, and implementing a quota management system for agricultural water use. HIGHLIGHTS The distribution of water resources in Ulanqab City is in a state of mismatch with social and economic development.; From 2011 to 2020, the water resources spatial equilibrium levels of six counties in Ulanqab City improved, while there was no significant change in five counties.; The vulnerability indicators of Ulanqab City are per capita water resources and ecological environment water demand load.;

Abstract Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.

Efficient translation mediated by the 5′ untranslated region (5′ UTR) is essential for the robust efficacy of mRNA vaccines. However, the N1-methyl-pseudouridine (m1Ψ) modification of mRNA can impact the translation efficiency of the 5′ UTR. We discovered that the optimal 5′ UTR for m1Ψ-modified mRNA (m1Ψ–5′ UTR) differs significantly from its unmodified counterpart, highlighting the need for a specialized tool for designing m1Ψ–5′ UTRs rather than directly utilizing high-expression endogenous gene 5′ UTRs. In response, we developed a novel machine learning-based tool, Smart5UTR, which employs a deep generative model to identify superior m1Ψ–5′ UTRs in silico. The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models. As a result, Smart5UTR can successfully design superior 5′ UTRs, greatly benefiting mRNA vaccine development. Notably, Smart5UTR-designed superior 5′ UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2, surpassing the performance of vaccines using high-expression endogenous gene 5′ UTRs.

The global spread and distribution of antibiotic resistance genes (ARGs) has received much attention whereas knowledge about the transmission of ARGs from one matrix to another is still insufficient. In this study, the paddy fields fertilized with chemical fertilizer, swine compost, and no fertilizer were investigated to assess the transfer of ARGs from soil to rice. Soil and plant samples were collected at day 0, 7, 30 and 79 representing various stages of paddy growth. High throughput qPCR was applied to quantify ARGs using a set of 144 primers. Gene copy number of ARGs measured in soil initially decreased and then increased in soil with no fertilizer and chemical fertilizer, indicating that crop planting and flooding conditions did influence the ARGs profiles in soil. Application of swine compost significantly enhanced the relative abundance and gene copy number of ARGs in paddy soil. Rice seedlings contained substantial amount of ARGs and their relative abundance continually decreased after transplant. Compared with initial stage, detection frequencies of ARGs increased in soil without swine compost at harvest time (day 79), indicating the transmission of ARGs from irrigation water to soil. Detection frequencies of ARGs increased in soil and rice root with swine compost at harvest time, indicating the transfer of ARGs from swine compost to soil and rice root. There was no significant difference in abundance and diversity of ARGs in rice grains with these three different fertilizations. The source of the ARGs in rice grain still needs further exploration.

Abstract Background There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near‐infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. Methods Five minutes resting‐state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting‐state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut‐off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. Results The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)‐based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR‐based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut‐off value of resting‐state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. Conclusion Resting‐state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut‐off values of resting‐state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients.

Protein post-translational modifications (PTMs) represent a crucial aspect of cellular regulation, occurring after protein synthesis from mRNA. These modifications, which include phosphorylation, ubiquitination, acetylation, methylation, glycosylation, Sumoylation, and palmitoylation, play pivotal roles in modulating protein function. PTMs influence protein localization, stability, and interactions, thereby orchestrating a variety of cellular processes in response to internal and external stimuli. Dysregulation of PTMs is linked to a spectrum of diseases, such as cancer, inflammatory diseases, and neurodegenerative disorders. UFMylation, a type of PTMs, has recently gained prominence for its regulatory role in numerous cellular processes, including protein stability, response to cellular stress, and key signaling pathways influencing cellular functions. This review highlights the crucial function of UFMylation in the development and progression of tumors, underscoring its potential as a therapeutic target. Moreover, we discuss the pivotal role of UFMylation in tumorigenesis and malignant progression, and explore its impact on cancer immunotherapy. The article aims to provide a comprehensive overview of biological functions of UFMylation and propose how targeting UFMylation could enhance the effectiveness of cancer immunotherapy strategies.

Abstract Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross‐contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy‐modified carbon nitride nanosheets (g‐C3N4‐VC Ns) coated on the non‐woven fabrics of the out layer of the mask, offering effective and long‐term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy‐disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron‐hole pairs, thus promoting the electron‐hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as‐prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self‐protection.

Abstract Objectives High‐grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. Methods In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression‐free survival (PFS) time using Kaplan–<>Meier survival analysis with log‐rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Results Kaplan–Meier survival analysis revealed that the 1‐, 2‐, and 5‐years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1‐, 2‐, and 5‐years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p

The extensive use of sulfonylurea herbicides has raised major concerns regarding their long-term soil residues and agroecological risks despite their role in agricultural protection. Microbial degradation is an important approach to remove sulfonylureas, whereas understanding the associated biodegradation mechanisms, enzymes, and physiological responses remains incomplete. Based on the rapid biodegradation of nicosulfuron by typical fungal isolate Talaromyces flavus LZM1, the dependency on cellular accumulation and environmental conditions, e.g. pH and nutrient supplies, was shown in the study. The biodegradation of nicosulfuron occurred intracellularly and followed the cascade of reactions including hydrolysis, Smile contraction rearrangement, hydroxylation, and opening of the pyrimidine ring. Besides 2-amino-4,6-dimethoxypyrimidine (ADMP) and 2-aminosulfonyl-N,N-dimethylnicotinamide (ASDM), numerous products and intermediates were newly identified and the structural forms of methoxypyrimidine and sulfonylurea bridge contraction rearrangement are predicted to be more toxic than nicosulfuron. The biodegradation should be enzymatically regulated by glycosylphosphatidylinositol transaminase (GPI-T) and P450s, which were manifested with the significant upregulation in proteomics. It is the first time that the hydrolysis of nicosulfuron into ADMP and ASDM have been associated with GPI-T. The integrated pathways of biodegradation were further elucidated through the involvement of various active enzymes. Except for the enzymatic catalysis, the physiological responses verified by metabolo-proteomics were critical not only to regulate material synthesis, uptake, utilization, and energy transfer but also to maintain antioxidant homeostasis, biodegradability, and tolerance of nicosulfuron by the differentially expressed metabolites, such as acetolactate synthase and 3-isopropylmalate dehydratase. The obtained results would help understand the biodegradation mechanism of sulfonylurea from chemicobiology and enzymology and promote the use of fungal biodegradation in pollution rehabilitation.

A high entropy interlayer (TiZrHfNb)95Al5 was successfully designed for vacuum diffusion bonding of GH4169 superalloy to Ti2AlNb alloy. The relationships between grain size, grain boundary, lattice mismatch and microhardness, elastic modulus, shear strength and fracture behaviors were revealed. The typical microstructure was Ti2AlNb/B2/Solid solution/(Ti, Zr, Hf)2(Ni, Nb)+(Ti, Zr, Hf)(Ni, Nb) + Solid solution/(Ti, Zr, Hf)(Ni, Nb) + (Cr, Ni, Fe)ss/(Cr, Ni, Fe)ss/Cr-rich(Cr, Ni, Fe)ss/Ni-rich(Cr, Ni, Fe)ss/GH4169. With the holding time increased, the shear strength overall increased and decreased sharply, and the highest shear strength reached 384 MPa at 980 °C for 90 min. The microstructure had anisotropic crystal orientation, and the joints of Zone Ш for 90 min consisted of 92.08 % HAGBs and 7.92 % LAGBs. The residual strains and stresses decreased when the holding time increased. Meanwhile, recrystallisation appeared in Zone Ш, and the increase in the recrystallisation rate led to grain refinement. The lattice mismatch between (Ti, Zr, Hf)(Ni, Nb) and (Cr, Ni, Fe)ss phases was 25.05 %, indicating that the interface was non-coherent, and (Ti, Zr, Hf)(Ni, Nb)+(Cr, Ni, Fe)ss phases were located at an elastic modulus dramatically changed interface. Thus, the cracks easily formed in this interface and led to joint fracture. Moreover, the fracture mechanism was brittle fracture.

Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.

Abstract Practical aqueous zinc‐ion batteries require low‐cost thin zinc anodes with long‐term reversible stripping/depositing. However, thin zinc anodes encounter more severe issues than thick zinc, such as dendrites and uneven stripping, resulting in subpar performance and limited lifetimes. Here, this work proposes a three‐in‐one zinc anode obtained by a large‐scale two‐step method to address the above issues. In a three‐in‐one zinc anode, the copper foil as an inactive current collector solves the gradual reduction of the active area when only the pure zinc as an active current collector. This work develops an automatic electroplating device that can continuously deposit a zinc layer on a conducting foil to meet the demand for zinc‐coated copper foils. The sodium carboxymethylcellulose (CMC)‐zinc fluoride (ZnF2) protective layer prevents direct contact between zinc and separator, and provides a uniform and sufficient supply of zinc ions. The CMC‐ZnF2‐coated copper foil performs up to 3000 reversible zinc deposition/stripping cycles with a cumulative capacity of 6 Ah cm−2 and an average Coulombic efficiency of 99.94%. The Zn||ZnVO cell using the three‐in‐one anode achieved a high capacity retention of over 70% after 15 000 cycles. The proposed three‐in‐one anode and the automatic electroplating device will facilitate industrialization of practical thin zinc anodes.

Abstract Currently, the typical combination therapy of programmed death ligand‐1 (PD‐L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation‐induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD‐L1 and transforming growth factor‐β (TGF‐β) dual‐downregulation method. Following this, IR‐TAM is prepared by conjugating mitochondria‐targeted heptamethine cyanine dye IR‐68 with oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self‐assembled with albumin (Alb) to form IR‐TAM@Alb nanoparticles. By doing this, tumor‐targeting IR‐TAM@Alb nanoparticle effectively reversed tumor hypoxia and depressed PD‐L1 and TGF‐β expression to sensitize RT. Meanwhile, due to the capacity of heptamethine cyanine dye in targeting RIPF and the function of TAM in depressing TGF‐β, IR‐TAM@Alb also ameliorated fibrosis development induced by RT.

Background: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. Methods: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. Results: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were − 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions. Conclusion: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.

In this paper, the dynamic behaviors and control strategies of a rumor propagation model are studied in multi-lingual environment. First, an S2E2I2R rumor propagation model is proposed, which incorporates a non-smooth inhibition mechanism. Meanwhile, the existence and stability of the equilibrium are analyzed, grounded in the spreader threshold of the government intervention. Finally, the optimal control and the event-triggered impulsive control strategies are proposed to mitigate the spread of rumors, and the comparison of their effectiveness is further presented by the numerical simulation and a practical case.

Abstract Purpose Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM. Methods Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions. Results The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90–1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97–1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM. Conclusions The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM.

Abstract Autophagy, the process of elimination of cellular components by lysosomal degradation, is essential for animal development and homeostasis. Using the autophagy-dependent Drosophila larval midgut degradation model we identified an autophagy regulator, the RING domain ubiquitin ligase CG14435 (detour). Depletion of detour resulted in increased early-stage autophagic vesicles, premature tissue contraction, and overexpression of detour or mammalian homologues, ZNRF1 and ZNRF2, increased autophagic vesicle size. The ablation of ZNRF1 or ZNRF2 in mammalian cells increased basal autophagy. We identified detour interacting proteins including HOPS subunits, deep orange (dor/VPS18), Vacuolar protein sorting 16A (VPS16A), and light (lt/VPS41) and found that detour promotes their ubiquitination. The detour mutant accumulated autophagy-related proteins in young adults, displayed premature ageing, impaired motor function, and activation of innate immunity. Collectively, our findings suggest a role for detour in autophagy, likely through regulation of HOPS complex, with implications for healthy aging.

Highlights Dense and flat freestanding Bi2Te3-based thermoelectric nano films were successfully fabricated by sputtering technology using a newly developed nano graphene oxide membrane as a substrate. On-chip micro temperature controllers were integrated using conventional micro-electromechanical system technology, to achieve energy-efficient temperature control for low-power electronics. The tunable equivalent thermal resistance enables an ultrahigh temperature control capability of 100 K mW−1 and an ultra-fast cooling rate exceeding 2000 K s−1, as well as excellent reliability of up to 1 million cycles.

Abstract Background Breastfeeding practices are influenced by the maternal-infant bond relationship. Mothers of preterm infants in the puerperium face many challenges and support is needed to maintain breastfeeding after hospital discharge. This study explored the breastfeeding experiences among mothers of preterm infants and challenges that influenced their breastfeeding practices. Methods A qualitative phenomenological approach was used involving the mothers of preterm infants during the puerperium in Shanghai who fulfilled the inclusion criteria and consented to participate in the study. The mothers were recruited using purposive sampling. Eighteen participants were interviewed using semi-structured in-depth interviews. All interviews were recorded in digital audio, transcribed verbatim, and analyzed using thematic analysis. Findings The breastfeeding experience among mothers of preterm infants included four themes: breastfeeding motivation, breastfeeding challenges, breastfeeding support and education, and response to parental stress. Breastfeeding challenges included perceived insufficient milk, bottle preference, and maternal-infant separation. Two sub-themes of breastfeeding support included breastfeeding knowledge and approach. Conclusion To overcome breastfeeding challenges and improve the breastfeeding rate of preterm infants after discharge, medical professionals must develop individualized breastfeeding plans based on a comprehensive assessment of the needs of mothers who delivered a preterm infant.

Brillouin fiber laser with the non-resonance pumping configuration, has compact set-up, good wavelength tunability and high-power single-frequency-emission capability, being regarded as an important technique for highly-coherent light generation. Such Brillouin fiber lasers, using single-mode fiber (SMF) as the Brillouin gain medium, generally have high lasing thresholds and mode-hopping instabilities, resulting from the relatively-low Brillouin gain coefficient of the conventional SMF. Here, we report a compact, non-resonance-pumping Brillouin photonic crystal fiber laser that can generate kHz-level-linewidth single-frequency lasing with tens-of-mW lasing threshold. Mode-hopping instability of this laser is largely suppressed thanks to the short (∼20 m) cavity length, which gives rise to a free-spectral-range (FSR) value of ∼10 MHz properly matching the tens-of-MHz Brillouin gain bandwidth. Experimental results of both self-heterodyne and frequency-noise measurements indicate a laser linewidth of ∼1.4 kHz, corresponding to high linewidth-narrowing ratio of ∼18. No lasing line of high-order Stokes was observed in experiments as the laser pump power was gradually increased to ∼200 mW, giving a nearly-linear lasing slope.

Spinal cord injury-induced motor dysfunction is associated with neuroinflammation. Studies have shown that the triterpenoid lupenone, a natural product found in various plants, has a remarkable anti-inflammatory effect in the context of chronic inflammation. However, the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown. In this study, we established an impact-induced mouse model of spinal cord injury, and then treated the injured mice with lupenone (8 mg/kg, twice a day) by intraperitoneal injection. We also treated BV2 cells with lipopolysaccharide and adenosine 5′-triphosphate to simulate the inflammatory response after spinal cord injury. Our results showed that lupenone reduced IκBα activation and p65 nuclear translocation, inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B, and enhanced the conversion of proinflammatory M1 microglial cells into anti-inflammatory M2 microglial cells. Furthermore, lupenone decreased NLRP3 inflammasome activation, NLRP3-induced microglial cell polarization, and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway. These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

The AlCoCrFeNi2.1 eutectic high-entropy alloy (Ni2.1 EHEA), as an exemplary representative of the high-entropy alloy family, has garnered significant research attention owing to its exceptional comprehensive properties. In this study, we investigated the influence of various growth velocities on the microstructure, lamellar spacing, and mechanical properties of the Ni2.1 EHEA. We observed that at lower growth velocities, the structure consisted of an alternating face-centered-cubic (FCC) phase and B2 phase lamellae aligned in a single direction, with the lamellae orientation parallel to the direction of the heat flow. The yield strength increased with the growth rate, while the ultimate tensile strength decreased with increasing the growth velocity. Ductility remained relatively consistent, and a double yield phenomenon was observed in the elastic-plastic deformation region. Under conditions of high growth velocities, the microstructure transitioned from a single-directional full lamellar structure to a multi-stage lamellar arrangement. The most favorable comprehensive mechanical properties were achieved at a growth rate of 200 μm/s, resulting in a yield strength of 450 MPa, an ultimate tensile strength of 1092 MPa, and a remarkable ductility of ∼32% in the directionally solidified samples—double that of the arc-melted sample. The evolution law of directional solidification structures under the coupling effect of different magnetic fields and different growth rates was studied. The interaction of the thermoelectric-magnetic force and thermoelectric-magnetic convection and the potential mechanism of microstructure evolution under the effect of magnetic field were deeply analyzed. The results reveal that at a growth rate of 2 μm/s, the spacing between eutectic layers decreases as the magnetic induction intensity increases, leading to the transformation of some regular layers into spherical layers. Similarly, at a growth velocity of 10 μm/s, the eutectic structure exhibited a Columnar-to-equiaxed transition (CET). However, as the growth rate further increases, the limited exposure time to the magnetic field prevented significant structural changes.

Abstract Shunt active power filter (SAPF) has emerged as a promising solution for mitigating harmonic distortions. Due to the interaction between the current inner‐loop of SAPF, source impedance and non‐linear loads, harmonic oscillation issue arises and adversely affects the stability of the system, thus in turn exacerbating the harmonic distortion. However, previous studies paid less attention to the value of phase adjustment in improving the dynamic behaviour of the loop and thus stabilizing harmonic oscillation. Taking the dynamic characteristics between source impedance and non‐linear load into consideration, this paper models and analyzes the SAPF system with source current direct control to reveal the law of full harmonic compensation oscillation. Based on the analysis, an enhanced phase adjustment strategy using load current feedforward is proposed and designed to stabilize harmonic oscillation, while maintaining a favourable trade‐off between stability and harmonic compensation performance. The small‐signal model validated for stability analysis and the effectiveness of proposed stabilization strategy are verified by simulation and experiment.

Additive manufacturing (AM) has gained significant attention in recent years owing to its ability to fabricate intricate shapes and structures that are often challenging or unattainable using conventional manufacturing techniques. This high-quality development trend entails higher requirements for the structural design of 3D printers. In this study, polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS) filaments were fed through a heated extrusion nozzle, which melted the material and deposited it onto a build platform. This study's objectives are high-gravitational material extrusion (HG-MEX) systems development, analyzing the high gravity influences on the flow behavior of materials during extrusion, and understanding the effects of gravitational on material flow and overall extrusion performance. HG-MEX systems have great potential for addressing various challenges in additive manufacturing, such as precise manufacturing. The highlight of the progress is that we developed an HG-MEX system and applied surface science to material extrusion in different gravity. We established a system and obtained results on different gravity, we analyzed the analogy between different gravity phenomena. We analyzed the interplay between the behavior of the fabricated parts and gravity. We analyzed high gravity effects on extrusion processes. The results confirmed the characteristics and feasibility of the developed system. The results suggest that a material extrusion line operating under 15 G conditions resulted in better printing quality compared to one operating under 1 G conditions. This observation implies that high gravity had a positive effect on the extrusion process, leading to improved material extrusion performance.

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P

Current research on maize germination suffers from long sampling intervals, and the relationship between the starch structure and the processing properties of flour in maize is still unclear. This study observed the effect of germination on the structure and composition of maize starch and the processing properties of maize flour over a 72 h period using a short interval sampling method. At 36 h, the short-range ordered structure, crystallinity, and enthalpy of starch reached the highest values of 1.02, 34.30%, and 9.90 J/g, respectively. At 72 h, the ratios of rapidly-digested starch (RDS) and slowly-digested starch (SDS) enhanced to 29.37% and 28.97%; the RS content reduced to 35.37%; and the flow properties of the starch were improved. This study enhances the understanding of the effects of germination on the processing properties of maize starch and flour, determines the appropriate application, and recommends the use of germination in the food industry.

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy.Main bodyA 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient’s condition.ConclusionThe combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

Liver cancer is one of the most prevalent forms of cancer worldwide. A significant proportion of patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, leading to unfavorable treatment outcomes. Generally, the development of HCC occurs in distinct stages. However, the diagnostic and intervention markers for each stage remain unclear. Therefore, there is an urgent need to explore precise grading methods for HCC. Machine learning has emerged as an effective technique for studying precise tumor diagnosis. In this research, we employed random forest and LightGBM machine learning algorithms for the first time to construct diagnostic models for HCC at various stages of progression. We categorized 118 samples from GSE114564 into three groups: normal liver, precancerous lesion (including chronic hepatitis, liver cirrhosis, dysplastic nodule), and HCC (including early stage HCC and advanced HCC). The LightGBM model exhibited outstanding performance (accuracy = 0.96, precision = 0.96, recall = 0.96, F1-score = 0.95). Similarly, the random forest model also demonstrated good performance (accuracy = 0.83, precision = 0.83, recall = 0.83, F1-score = 0.83). When the progression of HCC was categorized into the most refined six stages: normal liver, chronic hepatitis, liver cirrhosis, dysplastic nodule, early stage HCC, and advanced HCC, the diagnostic model still exhibited high efficacy. Among them, the LightGBM model exhibited good performance (accuracy = 0.71, precision = 0.71, recall = 0.71, F1-score = 0.72). Also, performance of the LightGBM model was superior to that of the random forest model. Overall, we have constructed a diagnostic model for the progression of HCC and identified potential diagnostic characteristic gene for the progression of HCC.

Metal based electroreflective devices (MERDs) have gained wide attention in recent years in the fields of smart windows and automotive glass due to their excellent photo-thermal modulation capability in the visible and near-infrared wavelength bands due to their high reflectivity. However, the high porosity due to the island-like growth of silver particles makes the devices susceptible to electrodeposited film breakage during prolonged energization or bleaching. This will seriously affect the effectiveness and stability of the device. In this paper, it is shown that the problem of Ag electrodeposition film fragmentation can be effectively overcome by replacing dimethyl sulfoxide solvent by N-methylpyrrolidone (NMP). The optical constants during film deposition were tested by the spectroscopic ellipsometry technique, and the porosity was calculated (reduced by 21.6%). The results show that MERDs with NMP as the solvent have more and more dispersed silver deposition sites, which leads to lower porosity of the silver deposited film during the deposition process. In addition, the lower turn-on voltage, greater contrast, longer memory effect, and greater coloring efficiency reveal that they are more promising for energy-saving applications.

BackgroudGastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work.Materials and methodsThis study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran’s Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P

Abstract Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl‐CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle‐type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6‐HMGCS1‐YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non‐alcoholic fatty liver diseases‐ associated HCC.

Abstract The emergence and rapid spread of antimicrobial resistance is of global public health concern. The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes (ARGs). In this review, we describe the reservoirs of gut ARGs and their dynamics in both animals and humans, use the One Health perspective to track the transmission of ARG‐containing bacteria between humans, animals, and the environment, and assess the impact of antimicrobial resistance on human health and socioeconomic development. The gut resistome can evolve in an environment subject to various selective pressures, including antibiotic administration and environmental and lifestyle factors (e.g., diet, age, gender, and living conditions), and interventions through probiotics. Strategies to reduce the abundance of clinically relevant antibiotic‐resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance. With the help of effective measures taken at the national, local, personal, and intestinal management, it will also result in preventing or minimizing the spread of infectious diseases. This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.

Abstract Background Danggui Buxue Decoction (DBD) is a traditional Chinese medicine prescription, which has the functions of benefiting Qi, generating blood and regulating the immune system. At present, various clinical reports suggest that DBD has some efficacy in Rheumatoid arthritis (RA), but its mechanism of action is still unclear. Thus, the present study explored mechanism of this preparation on RA. Methods The effect of DBD was evaluated by tumor necrosis factor (TNF)-α-induced Human fibroblast-like synoviocyte of rheumatoid arthritis (HFLS-RA) cell model and collagen-induced arthritis (CIA) rat model, respectively. Inflammatory factors including TNF-ɑ, IL-1β, IL-6 and IL-10 in the culture supernatants or rat serum were measured using ELISA. The related indexes including fur luster, mental state and activity of rat and the symptoms including swelling and deformation of toes and ankles were also measured. Results In vitro results showed that DBD cannot only inhibit the proliferation of HFLS-RA cells but also reduce the levels of pro-inflammatory factors while increasing the level of anti-inflammatory factors. Similar results were obtained from in vivo experiments. Rats receiving DBD showed a decrease in the severity of rheumatoid arthritis in rat models. Moreover, the protein levels of c-myc and β-catenin decreased significantly, while the protein level of SFRP4 increased, which indicated that DBD might inhibit the inflammatory reaction by regulating Wnt/β-catenin signaling pathway, thus alleviating the symptoms of RA. Conclusion Our findings not only provide insights for understanding the molecular mechanism of DBD in treating RA, but also provide the theoretical basis for further clinical prevention and treatment.

Abstract Purpose While coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, millions of patients with COVID-19 have recovered and returned to their families and work, although the key factors of sequela-free survival remain unknown. Here we determine key factors associated with sequela-free survival of patients with COVID-19. Methods Sequela-free survival is defined as having none of the long-term sequelae measured with the Activity of Daily Living (ADL) Scale, modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI) and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the key factors of sequela-free survival. Results The follow-up period for the 464 patients was 10 August to 30 September 2020. Of these, 424 patients completed the assessment of all scales. 30.2% (128 of 424) were categorised as sequela-free at follow-up. The most common sequelae were psychosocial problems (254 [57.7%]), respiratory function abnormality (149 [32.6%]) and cardiac function abnormality (98 [21.5%]). Risk factors associated with COVID-19 sequelae were anaemia on admission, longer duration from the onset of symptoms to admission and increasing of age, whereas anaemia treatment was a protective factor against sequelae. A haemoglobin level of

Abstract Classic biphasic pulmonary blastoma (CBPB), a distinct type of lung cancer, is a dual‐phasic tumor characterized by the co‐existence of low‐grade fetal adenocarcinoma and primitive mesenchymal stroma. Accounting for less than 0.1% of surgically removed lung cancers, CBPB commonly presents in individuals during their fourth to fifth decades of life, with smoking as a significant risk factor. The optimal management strategy entails surgical resection, supplemented by chemotherapy to improve prognosis. The frontline chemotherapeutic agents typically include platinum agents and etoposide, with preoperative neoadjuvant chemotherapy potentially enabling operability for initially inoperable cases. In recent years, targeted therapies, such as antiangiogenic agents, have emerged as promising new treatment strategies for CBPB. For patients exhibiting brain metastases or deemed inoperable, radiation therapy proves to be a crucial therapeutic component. CBPB prognosis is adversely affected by factors such as early metastasis, tumor size exceeding 5 cm, and tumor recurrence. In this regard, serological markers have been identified as valuable prognostic indicators. To exemplify, we recount the case of a 44‐year‐old female patient with CBPB, wherein serum lactate dehydrogenase levels showed significant diagnostic value. This report further incorporates a comprehensive review of CBPB literature from the past 22 years.

Abstract We introduce Version 2 of our widely used 1-km Köppen-Geiger climate classification maps for historical and future climate conditions. The historical maps (encompassing 1901–1930, 1931–1960, 1961–1990, and 1991–2020) are based on high-resolution, observation-based climatologies, while the future maps (encompassing 2041–2070 and 2071–2099) are based on downscaled and bias-corrected climate projections for seven shared socio-economic pathways (SSPs). We evaluated 67 climate models from the Coupled Model Intercomparison Project phase 6 (CMIP6) and kept a subset of 42 with the most plausible CO2-induced warming rates. We estimate that from 1901–1930 to 1991–2020, approximately 5% of the global land surface (excluding Antarctica) transitioned to a different major Köppen-Geiger class. Furthermore, we project that from 1991–2020 to 2071–2099, 5% of the land surface will transition to a different major class under the low-emissions SSP1-2.6 scenario, 8% under the middle-of-the-road SSP2-4.5 scenario, and 13% under the high-emissions SSP5-8.5 scenario. The Köppen-Geiger maps, along with associated confidence estimates, underlying monthly air temperature and precipitation data, and sensitivity metrics for the CMIP6 models, can be accessed at www.gloh2o.org/koppen .

Abstract Background Intrinsic capacity (IC) can better reflect the physical functioning of older adults. However, few studies have been able to systematically and thoroughly examine its influencing factors and provide limited evidence for the improvement of intrinsic capacity. The objective of this study was to provide a comprehensive description of the overall decline in intrinsic capacity among older persons in the community. Additionally, the study aimed to analyze the composition of the five domains of reduction, compare the rate of decline among older adults and investigate the factors that influence this decline. Methods This was a cross-sectional study conducted in the Chinese community. The self-designed general characteristics questionnaire was created based on the healthy aging framework and a systematic review. Intrinsic capacity was assessed with the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Community Health Record Management System (CHRMS), Mini Nutritional Assessment Brief Form (MNA-SF), and Short Physical Performance Battery (SPPB). The influencing factors of intrinsic capacity were investigated using stepwise logistic regression. Results A total of 968 older adults with a mean age of 71.00 (68.00, 76.75) were examined, and 704 older adults (72.7%) showed a decline in intrinsic capacity. There was a decline in at least one domain in 39.3% of older adults, with reductions in each domain ranging from 5.3% (psychological) to 52.4% (sensory). The study examined the composition of domains that experienced a decline in intrinsic capacity. It was found that a combination of sensory and locomotor domains showed the most significant decrease in 44.5% (n = 106) of individuals who experienced a decline in the two domains. Furthermore, a combination of sensory, cognitive, and locomotor domains exhibited a significant decrease in 51.3% (n = 44) of individuals who experienced a reduction in three domains. Lastly, a combination of sensory, vitality, cognitive, and locomotor domains showed the most significant decline in four domains, accounting for 60.0% (n = 15) of the population. Older adults had a higher risk of intrinsic capacity decline if they were older (95% CI:1.158–2.310), had lower education, lived alone (95% CI: 1.133–3.216), smoked (95% CI: 1.163–3.251), high Charlson Comorbidity Index (95% CI: 1.243–1.807) scores, did not regular exercise (95% CI:1.150–3.084), with lower handgrip strength (95% CI: 0.945–0.982). Conclusions We found a relatively high prevalence of intrinsic capacity; more attention should be paid to older adults who are older, less educated, live alone, and have more comorbidities. It is imperative to prioritize a healthy lifestyle among older persons who exhibit smoking habits, lack regular exercise, and possess inadequate handgrip strength.