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Abstract Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (n = 461,089), left handgrip strength (n = 461,026), and appendicular lean mass (n = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson’s Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055–0.423, adjusted P = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440–0.810, adjusted P = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095–0.530, adjusted P = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121–0.59, adjusted P = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.

Abstract Recently, with graph neural networks (GNNs) becoming a powerful technique for graph representation, many excellent GNN-based models have been proposed for processing heterogeneous graphs, which are termed Heterogeneous graph neural networks (HGNNs). However, existing HGNNs tend to aggregate information from either direct neighbors or those connected by short metapaths, thereby neglecting the higher-order information and global feature similarity information in heterogeneous graphs. In this paper, we propose a Multi-View Heterogeneous graph neural network (MV-HGNN) to aggregate these information. Firstly, two auxiliary views, specifically a global feature similarity view and a graph diffusion view, are generated from the original heterogeneous graph. Secondly, MV-HGNN performs two message-passing strategies to get the representation of different views. Subsequently, a transformer-based aggregator is used to get the semantic information. Subsequently, the representations of the three views are fused into a final composite representation. We evaluate our method on the node classification task over three commonly used heterogeneous graph datasets, and the results demonstrate that our proposed MV-HGNN significantly outperforms state-of-the-art baselines.

Abstract Background Ichang papeda (Citrus ichangensis), a wild perennial plant of the Rutaceae family, is a cold-hardy plant. WRKY transcription factors are crucial regulators of plant growth and development as well as abiotic stress responses. However, the WRKY genes in C. ichangensis (CiWRKY) and their expression patterns under cold stress have not been thoroughly investigated, hindering our understanding of their role in cold tolerance. Results In this study, a total of 52 CiWRKY genes identified in the genome of C. ichangensis were classified into three main groups and five subgroups based on phylogenetic analysis. Comprehensive analyses of motif features, conserved domains, and gene structures were performed. Segmental duplication plays a significant role in the CiWRKY gene family expansion. Cis-acting element analysis revealed the presence of various stress-responsive elements in the promoters of the majority of CiWRKYs. Gene ontology (GO) analysis and protein-protein interaction predictions indicate that the CiWRKYs exhibit crucial roles in regulation of both development and stress response. Expression profiling analysis demonstrates that 14 CiWRKYs were substantially induced under cold stress. Virus-induced gene silencing (VIGS) assay confirmed that CiWRKY31, one of the cold-induced WRKYs, functions positively in regulation of cold tolerance. Conclusion Sequence and protein properties of CiWRKYs were systematically analyzed. Among the 52 CiWRKY genes 14 members exhibited cold-responsive expression patterns, and CiWRKY31 was verified to be a positive regulator of cold tolerance. These findings pave way for future investigations to understand the molecular functions of CiWRKYs in cold tolerance and contribute to unravelling WRKYs that may be used for engineering cold tolerance in citrus.

Thermochemical conversions are pathways for biomass utilization to produce various value-added energy and chemical products. For the development of novel thermochemical conversion technologies, an accurate understanding of the reaction performance and kinetics is essential. Given the diversity of the thermal analysis techniques, it is necessary to understand the features and limitations of the reactors, ensuring that the selected thermal analysis reactor meets the specific need for reaction characterization. This paper provides a critical overview of the thermal analysis reactors based on the following perspectives: 1) gas flow conditions in the reactor, 2) particle's external and internal heat and mass transfer limitations, 3) heating rate, 4) temperature distribution, 5) nascent char production and reaction, 6) liquid feeding and atomization, 7) simultaneous sampling and analyzing of bed materials, and 8) reacting atmosphere change. Finally, prospects and future research directions in the development of analysis techniques are proposed.

Abstract Background Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium. Methods In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool. Results We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins. Conclusion This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.

Abstract Experiments of co-gasification of spirit-based distillers’ grains (SDG) and sewage sludge (SS) were carried out with red mud (RM) by using a self-designed fixed-bed gasifier. The effects of RM addition, gasification reaction temperature, SS and SDG blending ratio and other factors on the gasification reaction characteristics and synergism were investigated. The results are as follow: RM had catalytic effect on SS and SDG co-gasification, which can enhance the gasification reaction and H2 yield; increasing the temperature can enhance the gasification reaction and reduce the syngas H2/CO; with the increase of SDG, the H2 yield gradually grew; with the rise of SS, the gasification reaction gradually augmented. The catalytic mechanism was mainly due to the redox cycle of Fe2O3 in RM, which can promote the water transfer reaction. At the same time, the eutectic mixture of K, Na, Ca, Fe and other metal elements at high temperatures was the main reason for the synergistic effect.

Abstract Background To explore the efficacy of a prediction model based on diffusion‐weighted imaging (DWI) features extracted from deep learning (DL) and radiomics combined with clinical parameters and apparent diffusion coefficient (ADC) values to identify microsatellite instability (MSI) in endometrial cancer (EC). Methods This study included a cohort of 116 patients with EC, who were subsequently divided into training (n = 81) and test (n = 35) sets. From DWI, conventional radiomics features and convolutional neural network‐based DL features were extracted. Random forest (RF) and logistic regression were adopted as classifiers. DL features, radiomics features, clinical variables, ADC values, and their combinations were applied to establish DL, radiomics, clinical, ADC, and combined models, respectively. The predictive performance was evaluated through the area under the receiver operating characteristic curve (AUC), total integrated discrimination index (IDI), net reclassification index (NRI), calibration curves, and decision curve analysis (DCA). Results The optimal predictive model, based on an RF classifier, comprised four DL features, three radiomics features, two clinical variables, and an ADC value. In the training and test sets, this model exhibited AUC values of 0.989 (95% CI: 0.935–1.000) and 0.885 (95% CI: 0.731–0.967), respectively, demonstrating different degrees of improvement compared with the clinical, DL, radiomics, and ADC models (AUC‐training = 0.671, 0.873, 0.833, and 0.814, AUC‐test = 0.685, 0.783, 0.708, and 0.713, respectively). The NRI and IDI analyses revealed that the combined model resulted in improved risk reclassification of the MSI status compared to the clinical, radiomics, DL, and ADC models. The calibration curves and DCA indicated good consistency and clinical utility of this model, respectively. Conclusions The predictive model based on DWI features extracted from DL and radiomics combined with clinical parameters and ADC values could effectively assess the MSI status in EC.

ObjectiveCurrently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus.MethodsClinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC).ResultsA total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically.ConclusionThe established prediction model combining patient’s age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.

Background: In recent years, abnormal expression of collagen triple helix repeat containing 1 (CTHRC1) has been found in some tumors, closely related to the poor prognosis of cancer patients. However, the clinical significance of CTHRC1 in gliomas is not completely understood. Methods: We investigated the expression, prognostic value, and potential biological function of CTHRC1 in different types of gliomas through bioinformatics analysis and experimental verification. Results: Bioinformatics analysis revealed several key findings regarding the expression and clinical significance of CTHRC1 in gliomas. First, the analysis demonstrated a positive correlation between CTHRC1 expression and the World Health Organization (WHO) grading of gliomas, a relationship that was validated through immunohistochemistry experiments. In addition, a trend was observed in which CTHRC1 expression increased with the extent of glioma invasion, as supported by Western blot experiments. Subsequent bioinformatics analysis identified the mesenchymal subtype of gliomas as having the highest levels of CTHRC1 expression, a finding reinforced by immunohistochemical staining. Moreover, high CTHRC1 expression was associated with poor prognosis in gliomas and emerged as an independent prognostic factor, with varying impacts on prognosis between low-grade gliomas (LGGs) and glioblastoma (GBM) subgroups. Notably, comparative analysis unveiled distinct patterns of immune infiltration of CTHRC1 in LGG and GBM. Furthermore, alterations in copy number variations and DNA methylation were identified as potential mechanisms underlying elevated CTHRC1 levels in gliomas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that CTHRC1 and its associated genes mainly function in the extracellular matrix and participate in tumor-related signaling pathways. Conclusions: The CTHRC1 has shown significant clinical utility as a prognostic marker and mesenchymal subtype marker of glioma.

We report the controlled fabrication of nitrogen doped graphene (NG) nanoplates, which are uniformly decorated with iron nitride (Fe3N) nanoparticles, via ball milling of mixtures of graphite and iron nitrates and the following ammonia annealing. The obtained Fe3N@NG composites demonstrate excellent electrocatalytic activity and durability for oxygen evolution reaction, both of which outperform those of the state-of-the-art iridium oxide catalysts. This may be attributed to nitrogen doping as well as the synergistic effect between Fe3N and graphene nanoplates.

Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone lysine demethylase (KDM) playing an important role in epigenetic modification. Characterized by the zinc finger plant homology domain (PHD) and the Jumonji C (JmjC) domain, PHF8 preferentially binds to H3K4me3 and erases repressive methyl marks, including H3K9me1/2, H3K27me1, and H4K20me1. PHF8 is indispensable for developmental processes and the loss of PHF8 enzyme activity is linked to neurodevelopmental disorders. Moreover, increasing evidence shows that PHF8 is highly expressed in multiple tumors as an oncogenic factor. These findings indicate that studying the role of PHF8 will facilitate the development of novel therapeutic agents by the manipulation of PHF8 demethylation activity. Herein, we summarize the current knowledge of PHF8 about its structure and demethylation activity and its involvement in development and human diseases, with an emphasis on nervous system disorders and cancer. This review will update our understanding of PHF8 and promote the clinical transformation of its predictive and therapeutic value.

PHD (plant homeodomain) finger proteins emerge as central epigenetic readers and modulators in cancer biology, orchestrating a broad spectrum of cellular processes pivotal to oncogenesis and tumor suppression. This review delineates the dualistic roles of PHD fingers in cancer, highlighting their involvement in chromatin remodeling, gene expression regulation, and interactions with cellular signaling networks. PHD fingers’ ability to interpret specific histone modifications underscores their influence on gene expression patterns, impacting crucial cancer-related processes such as cell proliferation, DNA repair, and apoptosis. The review delves into the oncogenic potential of certain PHD finger proteins, exemplified by PHF1 and PHF8, which promote tumor progression through epigenetic dysregulation and modulation of signaling pathways like Wnt and TGFβ. Conversely, it discusses the tumor-suppressive functions of PHD finger proteins, such as PHF2 and members of the ING family, which uphold genomic stability and inhibit tumor growth through their interactions with chromatin and transcriptional regulators. Additionally, the review explores the therapeutic potential of targeting PHD finger proteins in cancer treatment, considering their pivotal roles in regulating cancer stem cells and influencing the immune response to cancer therapy. Through a comprehensive synthesis of current insights, this review underscores the complex but promising landscape of PHD finger proteins in cancer biology, advocating for further research to unlock novel therapeutic avenues that leverage their unique cellular roles.

Background: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. Methods and results: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. Conclusions: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.

BackgroundAlthough malnutrition has been shown to influence the clinical outcomes of Stroke Patients with Bulbar Paralysis (SPBP), the prevalence and influencing factors have yet to be uncovered.ObjectiveThis study aims to assess the current prevalence and factors associated with malnutrition in SPBP.MethodsA multicenter cross-sectional investigation was conducted among SPBP in China from 2019 to 2021. Information was collected on basic information, health condition, diagnosis, treatment, neurological function, activities of daily living, swallowing function, and nutritional status. A multivariable logistic regression model was used to identify the factors that influenced nutritional status. ROC analysis was used to assess the predictive value of each independent influencing factor and the logit model.ResultsIn total, 774 SPBP were enrolled, and the prevalence of malnutrition was 60.59%. Pulmonary infection [aOR:2.849, 95%CI: (1.426, 5.691)], hemoglobin [aOR: 0.932, 95%CI: (0.875, 0.982)], serum albumin [aOR: 0.904, 95%CI: (0.871, 0.938)], total protein [aOR: 0.891, 95%CI: (0.819, 0.969)], prealbumin [aOR: 0.962, 95%CI: (0.932, 0.993)], and National Institute of Health Stroke Scale (NIHSS) scores [aOR: 1.228, 95%CI: (1.054, 1.431)] were independent factors associated with malnutrition in SPBP. ROC analysis revealed that the logit model had the best predictive value [area under the curve: 0.874, 95% CI: (0.812, 0.936); specificity: 83.4%; sensitivity: 79.3%; p

BackgroundAlthough stroke-related dysphagia has been shown to influence quality of life (QOL), the underlying mechanisms have yet to be uncovered.ObjectiveThis study aims to investigate the mediating role of nutritional status and psychological disorders in the relationship between stroke-related dysphagia and QOL in stroke patients and explore the moderating effect of enteral nutrition mode.MethodsIn 2022, A questionnaire survey using stratified random sampling was conducted on 5,322 stroke patients with dysphagia, including Functional Oral Intake Scale (FOIS), Swallowing Quality of Life Questionnaire, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) to assess dysphagia, QOL and psychological disorders, respectively, for each participant. Records of serum albumin, Hemoglobin, Total serum protein, serum prealbumin and Body mass index were enrolled to assess nutritional status.ResultsFOIS demonstrated a significant positive predictive effect on QOL. Nutritional status and psychological disorders (PHQ-9 and GAD-7) mediated the relationship between FOIS and QOL. Nutritional status-psychological disorders showed a chain mediation effect in the relationship between FOIS and QOL. The moderating effect of enteral nutrition mode was observed.ConclusionThe mediating role of nutritional status and psychological disorders with moderating effect of enteral nutrition mode in the relationship between dysphagia and QOL in stroke patients was found.

Abstract Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin (HA) glycoprotein. The immunogenic subdominant stem domain of HA is highly conserved and can be recognized by antibodies capable of binding multiple HA subtypes. Therefore, the HA stem antigen is a promising target for the design of universal influenza vaccines. On the basis of an established lipid nanoparticle‐encapsulated mRNA vaccine platform, we designed and developed a novel universal influenza mRNA vaccine (mHAs) encoding the HA stem antigen of the influenza A (H1N1) virus. We tested the efficacy of the mHAs vaccine using a mouse model. The vaccine induced robust humoral and specific cellular immune responses against the stem region of HA. Importantly, two doses of the mHAs vaccine fully protected mice from lethal challenges of the heterologous H1N1 and heterosubtypic H5N8 influenza viruses. Vaccinated mice had less pathological lung damage and lower viral titers than control mice. These results suggest that an mRNA vaccine using the conserved stem region of HA may provide effective protection against seasonal and other possible influenza variants.

Abstract Broadband spectral photoresponse has shown bright prospects for various optoelectronic devices, while fulfilling high photoactivity beyond the material bandgap is a great challenge. Here, we present a molecular pyroelectric, N-isopropylbenzylaminium trifluoroacetate (N-IBATFA), of which the broadband photo-pyroelectric effects allow for self-driven wide spectral photodetection. As a simple organic binary salt, N-IBATFA possesses a large polarization (~9.5 μC cm−2), high pyroelectric coefficient (~6.9 μC cm−2 K−1) and figures-of-merits (F V = 187.9 × 10−2 cm2 μC−1; F D = 881.5 × 10−5 Pa−0.5) comparable to the state-of-art pyroelectric materials. Particularly, such intriguing attributes endow broadband photo-pyroelectric effect, namely, transient currents covering ultraviolet (UV, 266 nm) to near-infrared (NIR, 1950 nm) spectral regime, which breaks the restriction of its optical absorption and thus allows wide UV-NIR spectral photodetection. Our finding highlights the potential of molecular system as high-performance candidates toward self-powered wide spectral photodetection.

The 2022′s Youth Forum on Resources Chemicals and Materials was held on November 12–13, 2022, in Shenyang, Liaoning Province. Panel discussions focus on the cutting-edge researches on “Fine chemicals and advanced alloy materials” and “Utilization of fossil and renewable carbon resources”. This perspective summarizes the major directions of scientific research and technical developments aligned in the discussions. Fine chemical industry tends to pursue green and low-carbon products, intelligent product design, and start manufacturing. In recent years, great efforts have been made for transformation of cellulose into advanced electronic as well as life-service bio-materials and to the high-selectivity extraction of bio-base aromatic chemicals from lignin. Concerning high-end alloy materials, regulating deformation mechanism of crystal to construct bimodal microstructure seems highly prospective in harmonizing precipitate hardening effect and plastic deformation capacity. As we know, utilization of fossil carbon resources constitutes the major anthropogenic carbon emissions, and the related innovations thus should be, for possibly a long period, on increasing energy production efficiency and low-carbon cascaded conversion of fossil fuels, especially of coal.

Abstract Background The global delay in women’s reproductive age has raised concerns about age-related infertility. The decline in oocyte quality is a limiting factor of female fertility, yet there are currently no strategies to preserve oocyte quality in aged women. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aged oocytes. Methods For the in vivo experiments, the aged mice (8-month-old) were intraperitoneally injected with GH daily for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aged mice were treated with GH during oocyte maturation. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to assess oocyte quality, aneuploidy and developmental potential characteristics. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aged oocytes. Results In this study, we demonstrated that GH supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, we discovered that GH supplementation reduced aneuploidy in aged oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the MAPK3/1 pathway may be involved in the reduction in aneuploidy of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 may also act as a mediator in how GH regulates MAPK3/1. Conclusions In conclusion, our research reveals that GH supplementation protects oocytes against aging-related aneuploidy and enhances the quality of aged oocytes, which has clinical significance for aged women undergoing assisted reproduction technology. Graphical Abstract

BackgroundPost-stroke fatigue is a typical complication following stroke. However, existing research primarily focused on its underlying mechanisms, and its impact on rehabilitation outcomes has yet to be uncovered.ObjectiveThis study aims to explore the impact of post-stroke fatigue on rehabilitation outcomes during hospitalization.MethodThis was a prospective multicenter observational study including 46 stroke patients receiving comprehensive rehabilitation treatment. Patients' basic information was recorded upon admission and patients' functional independence was assessed with Functional Independence Measure (FIM) both upon admission and discharge. One week after rehabilitation treatment, fatigue, positivity in daily activity, attention, and memory were assessed. Serum biochemical indicators and levels of C-reactive protein (CRP) were assessed weekly following admission. The pain scores were assessed during the first week of hospitalization to calculate the average. Correlation analysis, linear regression and propensity score matching (PSM) were used to analyze the impact of fatigue on FIM scores at discharge and length of hospital stay.ResultThe proportion of patients with low fatigue was 39.13% and significant improvement was revealed in FIM scores upon admissions and discharge [(50.67±18.61) vs. (75.13±21.04), PConclusionPost-stroke fatigue can affect the rehabilitation outcomes regarding motor function independence and length of hospital stay.

An appropriate wound dressing is necessary to enhance the recovery of wounds and the restoration of tissue after the skin gets injured. In this study, a hollow porous microfiber (HPMF) scaffold composed of a combination of polylactic acid (PLA)/polybutylene adipate/butylene terephthalate (PBAT)/polyvinyl alcohol (PVA) was developed using coaxial electrospinning for wound healing. The porous structure of PLA/PBAT HPMFs was formed by dissolving PVA in water. The results showed that when maintaining a PLA: PBAT weight ratio of 7:3, high-quality porous PLA/PBAT composites were achieved, leading to a 36.25% increase in toughness and a 4.9% increase in biodegradability compared to pure PLA. Furthermore, in vivo wound healing assays suggest that composites successfully loaded can effectively promote wound healing on the 13th day. Therefore, this work underscores the significant potential of PLA/PBAT HPMF dressing for wound repair.

Background: Acute liver injury (ALI) is a common side effect of cisplatin treatment in the clinic and can lead to liver failure if not treated promptly. Previous studies have revealed that Limonin, a critical bioactive substance in citrus fruits, can protect multiple organs from various medical conditions. However, whether Limonin could ameliorate cisplatin-induced ALI remains unclear. Methods: In vivo and in vitro models were induced by cisplatin in the present study. Non-targeted metabolomics was employed to analyze the metabolic changes in the liver after ALI. In addition, molecular docking was utilized to predict the potential targets of Limonin. Results: Limonin attenuated hepatic histopathological injury by reducing hepatocyte apoptosis, lipid peroxidation, and inflammation in cisplatin-challenged mice. Employing metabolomics, we revealed that Limonin mediated the balance of various disturbed metabolic pathways in the liver after cisplatin-induced ALI. Integrating public data mining, molecular docking studies, and in vitro experiments demonstrated that Limonin suppressed the expression and activity of its direct target, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in the liver, thus reducing the production of corticosterone (CORT), a key metabolite promoted hepatocyte apoptosis. Conclusions: Limonin improves the liver metabolic microenvironment by inhibiting 11β-HSD1 to protect against cisplatin-induced ALI.

ABSTRACTAlthough previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts (LRTs) of children with Mycoplasma pneumoniae pneumonia (MPP). Here, we analysed the microbial community using 16S rRNA gene sequencing. Finally, bronchoalveolar lavage fluid (BALF) samples from 158 children with MPP and 29 with bacterial or viral pneumonia (control group) were collected. The diversity of the microbial community was significantly different between the two groups. A significantly increased abundance of Tenericutes and Mycoplasma was detected in the MPP group, exceeding 67% and 65% of the total bacterial population, respectively. Using Mycoplasma abundance as the diagnostic method, the sensitivity and specificity of the model was 97.5% and 96.6%, respectively. Compared to the mild MPP group, lower alpha diversity and significantly increased Mycoplasma abundance were found in the severe MPP group (P

Abstract The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development. However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear. Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo. In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway. Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC.

Abstract Halide double perovskites have recently emerged as an environmentally green candidate toward electronic and optoelectronic applications owing to their non-toxicity and versatile physical merits, whereas study on high-temperature antiferroelectric (AFE) with excellent anti-breakdown property remains a huge blank in this booming family. Herein, we present the first high-temperature AFE of the lead-free halide double perovskites, (CHMA)2CsAgBiBr7 (1, where CHMA+ is cyclohexylmethylammonium), by incorporating a flexible organic spacer cation. The typical double P-E hysteresis loops and J-E curves reveal its concrete high-temperature AFE behaviors, giving large polarizations of ~4.2 μC/cm2 and a high Curie temperature of 378 K. Such merits are on the highest level of molecular AFE materials. Particularly, the dynamic motional ordering of CHMA+ cation contributes to the formation of antipolar alignment and high electric breakdown field strength up to ~205 kV/cm with fatigue endurance over 104 cycles, almost outperforming the vast majority of molecule counterparts. This is the first demonstration of high-temperature AFE properties in the halide double perovskites, which will promote the exploration of new “green” candidates for anti-breakdown energy storage capacitor.

Gene expression of cells is a heterogeneous and dynamic program involved in various biological processes. Here, authors develop Well-TEMPseq, a high-throughput, cost-effective, and accurate method for massively parallel profiling of the temporal dynamics of single-cell gene expression.

Iodine, primarily in the form of iodide (I−), is the bioavailable form for the thyroid in the human body. Both deficiency and excess intake of iodide can lead to serious health issues, such as thyroid disease. Selecting iodide ions among anions has been a significant challenge for decades due to interference from other anions. In this study, we designed and synthesized a new pincer-type acridine–triazole fluorescent probe (probe 1) with an acridine ring as a spacer and a triazole as a linking arm attached to two naphthol groups. This probe can selectively recognize iodide ions in a mixed solvent of THF/H2O (v/v, 9/1), changing its color from colorless to light yellow, making it suitable for highly sensitive and selective colorimetric and fluorescent detection in water systems. We also synthesized another molecular tweezer-type acridine–triazole fluorescent probe (probe 2) that exhibits uniform detection characteristics for iodide ions in the acetonitrile system. Interestingly, compared to probe 2, probe 1 can be detected by the naked eye due to its circulation effect, providing a simple method for iodine detection. The detection limit of probe 1 is determined to be 10−8 mol·L−1 by spectrometric titration and isothermal titration calorimetry measurements. The binding stoichiometry between probe 1 and iodide ions is calculated to be 1:1 by these methods, and the binding constant is 2 × 105 mol·L−1.

Background: Acute kidney injury (AKI) is a known complication of cisplatin administration; currently, there are no effective ways to prevent it. Therefore, it largely limited the use of cisplatin in chemotherapy in the clinic. In this study, we reported that Limonin, a triterpenoid compound extracted from citrus, alleviated cisplatin-induced AKI through metabolic reprogramming in the diseased kidneys. Methods: Cisplatin was employed to induce AKI in mice. Three groups were set up: Sham, cisplatin + vehicle, and cisplatin + Limonin. Using UHPLC-TOF/MS, we conducted metabolomics to profile the kidneys' endogenous metabolites and metabolic pathways. A network pharmacological method was performed to identify the targets of Limonin on AKI. The human proximal tubular epithelial cell line (HK-2) was applied for in vitro studies. Results: Limonin preserved serum creatinine and blood urea nitrogen levels after cisplatin-induced AKI. Employing metabolomics, we identified 33 endogenous differentially expressed metabolites and 7 significantly disturbed metabolic pathways in the diseased kidneys within three groups. After AKI, Limonin significantly reduced linoleic acid and its downstream product, arachidonic acid, thus exerting a protective effect on the kidney. The network pharmacological method identified CYP3A4 as a key target of Limonin in treating AKI, while CYP3A4 also serve as a mediator of arachidonic acid metabolism. In vitro, Limonin markedly reduced the level of arachidonic acid and HK-2 cell apoptosis triggered by cisplatin, mainly related to the targeted inhibition of CYP3A4-mediated arachidonic acid metabolism. Conclusion: Limonin ameliorates cisplatin-induced AKI by inhibiting CYP3A4 activity to regulate arachidonic acid metabolism, ultimately preserving kidney function.

Abstract Recently, graph contrastive learning (GCL) has achieved remarkable performance in graph representation learning. However, existing GCL methods usually follow a dual-channel encoder network (i.e., Siamese networks), which adds to the complexity of the network architecture. Additionally, these methods overly depend on varied data augmentation techniques, corrupting graph information. Furthermore, they are heavily reliant on large quantities of negative nodes for each object node, which requires tremendous memory costs. To address these issues, we propose a novel and simple graph representation learning framework, named SimGRL. Firstly, our proposed network architecture only contains one encoder based on a graph neural network instead of a dual-channel encoder, which simplifies the network architecture. Then we introduce a distributor to generate triplets to obtain the contrastive views between nodes and their neighbors, avoiding the need for data augmentations. Finally, we design a triplet loss based on adjacency information in graphs that utilizes only one negative node for each object node, reducing memory overhead significantly. Extensive experiments demonstrate that SimGRL achieves competitive performance on node classification and graph classification tasks, especially in terms of running time and memory overhead.

Highlights PLCD1 is methylated and downregulated in RCC and functions as a tumor suppressor gene Inactivation of PLCD1 contributes to RCC tumorigenesis. PLCD1 inhibits WNT/β-catenin and EGFR-FAK-ERK signaling in RCC.

Abstract Aberrant expression of circRNAs is closely associated with the progression of gastric cancer; however, the specific mechanisms involved remain unclear. Our aim was to identify new gastric cancer biomarkers and explore the molecular mechanisms of gastric cancer progression. Therefore, we analyzed miRNA and circRNA microarrays of paired early-stage gastric cancer samples. Our study identified a new circRNA called hsa_circ_0069382, that had not been reported before and was expressed at low levels in gastric cancer tissues. Our study also included bioinformatics analyses which determined that the high expression of hsa_circ_0069382 regulated the BTG anti-proliferation factor 2 (BTG2)/ focal adhesion kinase (FAK) axis in gastric cancer lines by sponging for miR-15a-5p. Therefore, proliferation, invasion, and migration of gastric cancer is impacted. miR-15a-5p overexpression partially restored the effects of hsa_circ_0069382. This study provides potential new therapeutic options and a future direction to explore for gastric cancer treatment, and biomarkers. Graphical Abstract

Abstract Hypergraphs, as a powerful representation of information, effectively and naturally depict complex and non-pair-wise relationships in the real world. Hypergraph representation learning is useful for exploring complex relationships implicit in hypergraphs. However, most methods focus on the 1-order neighborhoods and ignore the higher order neighborhood relationships among data on the hypergraph structure. These often result in underutilization of hypergraph structure. In this paper, we exploit the potential of higher order neighborhoods in hypergraphs for representation and propose a Multi-Order Hypergraph Convolutional Network Integrated with Self-supervised Learning. We first encode the multi-channel network of the hypergraph by a high-order spectral convolution operator that captures the multi-order representation of nodes. Then, we introduce an inter-order attention mechanism to preserve the low-order neighborhood information. Finally, to extract valid embedding in the higher order neighborhoods, we incorporate a self-supervised learning strategy based on maximizing mutual information in the multi-order hypergraph convolutional network. Experiments on several hypergraph datasets show that the proposed model is competitive with state-of-the-art baselines, and ablation studies show the effectiveness of higher order neighborhood development, the inter-order attention mechanism, and the self-supervised learning strategy.

The presented method was developed to determine the concentration of thymol residues in honey by ultra performance liquid chromatography with a fluorescence detector. The thymol in honey was extracted by 40% acetonitrile-water solution. After centrifugation and filtration, the separation of thymol was performed on an Accucore aQ liquid chromatography column (150 mm×2.1 mm, 2.6 μm) with the gradient elution of acetonitrile and water (containing 0.1% formic acid) as mobile phases, and quantitated by external standard method with fluoresce detector (excitation wavelength 274 nm, emission wavelength 297 nm). A good linear relationship (R2=0.9999) was observed with concentration ranging from 0.01 μg/mL to 3.00 μg/mL. The average recovery of thymol was from 87.4% to 106.9%, the coefficient of variation was between 0.7% and 7.3%, and the limit of quantification was 0.10 mg/kg. The developed method was applied to determine residual thymol in 48 commercial honey samples, and the thylmol was only detected in one sample. The presented method is simple, quick, reliable, and suitable to be used for batch screening and quantitative determination of residual thymol in honey.

Whether protein samples should be pretreated to remove nonspecific binding proteins in co-immunoprecipitation (CO-IP) is controversial. In this work, nonspecific binding of proteins to agarose beads was found to be greater than that to magnetic beads. The nonspecific binding was increased with the decrease of ion concentrations but reduced by Nonidet P40. Western blot indicated that p65 and β-actin were present as nonspecifically bound protein to the beads. p53 and β-actin were present in the CO-IP precipitates of nuclear proteins but pretreatment cleared the nonspecifically pulled down p53 and β-actin. These data suggest that magnetic beads are better for CO-IP, but preclearing is necessary to minimize false positive regardless of which bead is used, particularly for nuclear proteins.

Abstract Purpose With the improvement of people’s life expectancy, the incidence of stroke is high in the world. Post-stroke Dysphagia seriously affects people’s quality of life, among which malnutrition and pulmonary infection are the most common complications of post-stroke Dysphagia. At this point, it is very important to choose the right enteral and parenteral feeding mode. Current nutrition methods commonly used in patients with dysphagia after stroke include Intermittent oral to esophageal tube feeding (IOE), Nasogastric tube (NG), Nasal Jejunal feeding tubes (NJ), Percutaneous endoscopic gastrostomy (PEG).The purpose of this meta-analysis was to study the prognosis of patients with dysphagia after stroke who chose different nutritional methods. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTS) to examine the effects of different nutritional modalities on outcomes in patients with post-stroke dysphagia. We searched the Cochrane Library, PubMed, Medline, China National Knowledge Infrastructure (CNKI), Wanfang, and the VIP database. The search period is from the library's establishment to December 31, 2021.At least 2 reviewers independently assessed eligibility criteria, extracted data, and assessed the risk of bias. Standardized mean difference (SMD), relative risk (RR), and odds ratio (OR) were calculated using a random-effects model. Results Fourteen studies were identified across six databases that met the inclusion criteria, The results of meta-analysis showed that Intermittent oral to esophageal tube feeding (IOE) could improve the nutritional levels of patients better than nasogastric tube (NG) (MD 1.95, 95%CI 1.22–2.67, P

Abstract With the awareness of global environmental protection, the generation of photovoltaic (PV) power is increasing rapidly. Local voltage/Var control is widely studied to overcome the real‐time change in PV power generation. The stability condition of local controls is strictly dependent on the system information, and the control parameter is chosen considering both the stability condition and dynamic performance, which limits its scalability and makes the parameter setting difficult. In this work, the coupling between node voltages is separated in the prediction time, and a local voltage predictive control strategy is proposed to reduce the voltage deviation with respect to the reference voltage. The proposed control is implemented by using historical local data and current local measurements. The control parameter is the data length, which has less correlation with the system information, and the control performance is less sensitive to the control parameter. The proposed control can be regarded as a conventional local control with dynamic compensation, which improves the dynamic performance and the steady‐state error. The proposed local control is tested on a practical distribution system. The simulation result demonstrates the proposed control achieves better performance than the conventional local control under different application scenarios and weather conditions.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving, bringing great challenges to the control of the virus. In the present study, we investigated the characteristics of SARS-CoV-2 within-host diversity of human hosts and its implications for immune evasion using about 2,00,000 high-depth next-generation genome sequencing data of SARS-CoV-2. A total of 44% of the samples showed within-host variations (iSNVs), and the average number of iSNVs in the samples with iSNV was 1.90. C-to-U is the dominant substitution pattern for iSNVs. C-to-U/G-to-A and A-to-G/U-to-C preferentially occur in 5′-CG-3′ and 5′-AU-3′ motifs, respectively. In addition, we found that SARS-CoV-2 within-host variations are under negative selection. About 15.6% iSNVs had an impact on the content of the CpG dinucleotide (CpG) in SARS-CoV-2 genomes. We detected signatures of faster loss of CpG-gaining iSNVs, possibly resulting from zinc-finger antiviral protein-mediated antiviral activities targeting CpG, which could be the major reason for CpG depletion in SARS-CoV-2 consensus genomes. The non-synonymous iSNVs in the S gene can largely alter the S protein’s antigenic features, and many of these iSNVs are distributed in the amino-terminal domain (NTD) and receptor-binding domain (RBD). These results suggest that SARS-CoV-2 interacts actively with human hosts and attempts to take different evolutionary strategies to escape human innate and adaptive immunity. These new findings further deepen and widen our understanding of the within-host evolutionary features of SARS-CoV-2. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019, has evolved rapidly since it was discovered. Recent studies have pointed out that some mutations in the SARS-CoV-2 S protein could confer SARS-CoV-2 the ability to evade the human adaptive immune system. In addition, it is observed that the content of the CpG dinucleotide in SARS-CoV-2 genome sequences has decreased over time, reflecting the adaptation to the human host. The significance of our research is revealing the characteristics of SARS-CoV-2 within-host diversity of human hosts, identifying the causes of CpG depletion in SARS-CoV-2 consensus genomes, and exploring the potential impacts of non-synonymous within-host variations in the S gene on immune escape, which could further deepen and widen our understanding of the evolutionary features of SARS-CoV-2.

ABSTRACT The rates of antibiotic resistance of Helicobacter pylori are increasing, and the patterns of resistance are region and population specific. Here, we elucidated the antibiotic resistance pattern of H. pylori in a single center in China and compared short-read- and long-read-based whole-genome sequencing for identifying the genotypes. Resistance rates of 38.5%, 61.5%, 27.9%, and 13.5% against clarithromycin, metronidazole, levofloxacin, and amoxicillin were determined, respectively, while no strain was resistant to tetracycline or furazolidone. Single nucleotide variations (SNVs) in the 23S rRNA and GyrA/B genes revealed by Illumina short-read sequencing showed good diagnostic abilities for clarithromycin and levofloxacin resistance, respectively. Nanopore long-read sequencing also showed a good efficiency in elucidating SNVs in the 23S rRNA gene and, thus, a good ability to detect clarithromycin resistance. The two technologies displayed good consistency in discovering SNVs and shared 76% of SNVs detected in the rRNA gene. Taking Sanger sequencing as the gold standard, Illumina short-read sequencing showed a slightly higher accuracy for discovering SNVs than Nanopore sequencing. There are two copies of the rRNA gene in the genome of H. pylori, and we found that the two copies were not the same in at least 26% of the strains tested, indicating their heterozygous status. Especially, three strains harboring a 2143G/A heterozygous status in the 23S rRNA gene, which is the most important site for clarithromycin resistance, were found. In conclusion, our results provide evidence for an empirical first-line treatment for H. pylori eradication in clinical settings. Moreover, we show that Nanopore sequencing is a potential tool for predicting clarithromycin resistance. IMPORTANCE Helicobacter pylori resistance has been increasing in recent years. The resistance profile, which is important for empirical treatment, is region and population specific. We found high rates of resistance to metronidazole, clarithromycin, and levofloxacin in H. pylori in our center, while no resistance to tetracycline or furazolidone was found. These results provide a reference for local physicians prescribing antibiotics for H. pylori eradication. Nanopore sequencing recently appeared to be a promising technology for elucidating whole-genome sequences, which generates long sequencing reads and is time-efficient and portable. However, a relatively higher error rate of sequencing reads was also found. In this study, we compared Nanopore sequencing and Illumina sequencing for revealing single nucleotide variations in the 23S rRNA gene, which determines clarithromycin resistance, and we found that although there were a few false discoveries, Nanopore sequencing showed good consistency with Illumina sequencing, indicating that it is a potential tool for predicting clarithromycin resistance.

Located in the frontline against the largest population of microbiota, the intestinal mucosa of mammals has evolved to become an effective immune system. γδ T cells, a unique T cell subpopulation, are rare in circulation blood and lymphoid tissues, but rich in the intestinal mucosa, particularly in the epithelium. Via rapid production of cytokines and growth factors, intestinal γδ T cells are key contributors to epithelial homeostasis and immune surveillance of infection. Intriguingly, recent studies have revealed that the intestinal γδ T cells may play novel exciting functions ranging from epithelial plasticity and remodeling in response to carbohydrate diets to the recovery of ischemic stroke. In this review article, we update regulatory molecules newly defined in lymphopoiesis of the intestinal γδ T cells and their novel functions locally in the intestinal mucosa, such as epithelial remodeling, and distantly in pathological setting, e.g., ischemic brain injury repair, psychosocial stress responses, and fracture repair. The challenges and potential revenues in intestinal γδ T cell studies are discussed.

Sustained drug release has attracted increasing interest in targeted drug therapy. However, existing methods of drug therapy suffer drug action time, large fluctuations in the effective concentration of the drug, and the risk of side effects. Here, a biodegradable composite of polybutylene adipate co-terephthalate/polyvinylpyrrolidone (PBAT/PVP) consisting of electrospun hollow microspheres as sustained-released drug carriers is presented. The as-prepared PBAT/PVP composites show faster degradation rate and drug (Erlotinib) release than that of PBAT. Furthermore, PBAT/PVP composites loaded with Erlotinib provide sustained release effect, thus achieving a better efficacy than that after the direct injection of erlotinib due to the fact that the composites allow a high drug concentration in the tumor for a longer period. Hence, this work provides a potential effective solution for clinical drug therapy and tissue engineering using drug microspheres with a sustained release.

Background: Cervical stump cancer is a rare disease, which is subsequent to a previous subtotal hysterectomy. Among patients who underwent a subtotal hysterectomy, approximately 1%–3% develop cervical stump cancer which represents 3%–9% of all the cervical cancers. Methods: After acquiring consent from our ethics committee, we recruited the subjects and reviewed the patients’ data of those who were admitted to our hospital from January 2010 to December 2022. Written informed consent from all the study participants was acquired, and all materials complied with the Declaration of Helsinki and ethical standards. The patients’ data records, including clinical characteristics, treatment methods, human papillomavirus (HPV) infection conditions before the operation, complications of the treatment and follow-up status were analyzed. The HPV infection status was detected by Tellgen systems (Tellgen Corporation, Shanghai, China). SPSS software (Version 22.0, IBM Company, Armonk, NY, USA) was used for data analysis. Data is shown as mean ± standard deviation. A two-side p value < 0.05 was considered to be significant. Results: There were 127 cases with cervical stump cancer treated in our hospital during this period. The interval time between subtotal hysterectomy and stump cancer was 130.7 months. Vaginal bleeding, postcoital bleeding and pelvic pain were the main symptom. Seventy-two cases were squamous cancer and adenocarcinoma occurred in 39 cases. All patients received surgery or concurrent chemoradiotherapy. One hundred and ten cases were included in the follow-up. The median observation time was 65 months. Vaginal bleeding, gastrointestinal symptoms and vaginal contracture were the most common complications. The median observation time was 65 months and the 5-year disease-free rate for all patients was 51.8% with the 5-year overall survival for all patients being 77.3%. Conclusions: Subtotal hysterectomy results in a potential to develop cervical stump cancer. Cytological studies, cervical biopsy and endocervical curettage should be considered before a subtotal hysterectomy is performed. The patients should be well informed of the risk for retaining the cervical stump and further cervical stump cancer screening is mandatory.

Abstract Gastric cancer is a gastrointestinal tumor with high morbidity and mortality rates. Several factors influence its progression, cell death being an important element. In this review, we summarized the effects of necrosis, apoptosis, necroptosis, pyroptosis, ferroptosis, and eight less common cell death modalities on gastric cancer cells and the tumor microenvironment, detailed the molecular mechanisms of various cell death and their major regulatory pathways in gastric cancer, explored the prevalence and complexity of cell death in gastric cancer progression and highlighted the potentials of cell death-related therapies in gastric cancer.

Micro reactors are the essential part of thermal analysis techniques for characterizing gas-solid thermochemical reactions. The dynamic and diversified needs for investigating various complex materials and gas-solid reactions have led to the development of a variety of different microreactors over the years. Solid particles in microreactors are normally heated by furnaces from outside, resistive elements from inside, direct contact with bed particles, or other non-resistively methods. Solid particles can be fixed or fluidized in reactors where gas-solid contacts vary from diffusion-dominated to nearly diffusion-free conditions. Based on these characteristics, in this article we presented a broad classification for microreactors used for thermal analysis of gas-solid reactions. For each of the most popularly used microreactors, their features and limitations are briefly reviewed. By addressing the diversity of the microreactors used in the field of thermal analysis, the review aims at providing general guidance for the selection and operation of the microreactor to satisfy one's practical specific needs.

Abstract Background The most common complications of myomectomy are intraoperative hemorrhage and postoperative adhesion. The key point to overcome this problem is to improve suture quality. However, to date, there is still no consensus on the optimal method of uterine repair. In this study, we explored the effectiveness and feasibility of single-site laparoscopic parallel mattress sutures to reduce intraoperative bleeding and postoperative adhesion. Methods A retrospective cohort analysis was performed, according to the STROBE guidelines, on 124 patients with intramural fibroids admitted between May 2020 and April 2021. The cases were divided into two groups based on the description of the uterine incision suture in the surgical records, including 68 cases in the parallel mattress suture (PMS) group and 56 cases in the simple continuous suture (SCS) group. Operation-related indicators, bleeding indicators, surgical complications, scar reduction index 1 month after surgery, and the incidence of chronic pelvic pain 6 months after the surgery were observed. Independent sample t-tests and Mann–Whitney U tests were performed for the measurement data, and Pearson Chi-square tests were performed for count data. Statistical significance was set at P

Abstract Background Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. This study aimed to solve this problem in view of cellular metabolism. Methods Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. Results Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. Conclusions The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. Graphical abstract Video Abstract

The removal of radiocesium from acidic solutions is challenging. Here, the authors report the rapid and highly selective capture of cesium(I) from strongly acidic solutions by a robust layered metal sulfide.

Abstract Thyroid cancer remains the most prevailing endocrine malignancy, and a progressively increasing incidence rate has been observed in recent years, with 95% of thyroid cancer represented by differentiated thyroid carcinomas. The genetics and epigenetics of thyroid cancer are gradually increasing, and gene mutations and methylation changes play an important roles in its occurrence and development. Although the role of RAS and BRAF mutations in thyroid cancer have been partially clarified,but the pathogenesis and molecular mechanisms of thyroid cancer remain to be elucidated. Epigenetic modification refer to genetic modification that does not change the DNA sequence of a gene but causes heritable phenotypic changes in its expression. Epigenetic modification mainly includes four aspects: DNA methylation, chromatin remodelling, noncoding RNA regulation, and histone modification. This article reviews the importance of thyroid cancer epigenetic modification and BRAF gene mutation in the treatment of thyroid cancer.

One of the most common primary bone malignant tumors is osteosarcoma (OS), possessing a high tendency of local invasion and distant metastasis. Although surgery combined with chemotherapy can extend the patients’ survival time, the prognosis for most patients with metastases or relapses is poor. Immunotherapy has been proved to be a promising treatment alternative for malignant tumors. Although there is a significant amount of animal- and cell-based evidence supporting the relationship between immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) and cancers, no pan-cancer analysis is available. Simultaneously, immune checkpoint inhibitors have demonstrated satisfactory clinical results in some tumors; however, only a small fraction of patients with certain cancer types have been benefitted. Therefore, based on the TCGA dataset, we first explored the potential roles of immune checkpoints in 33 tumors. Programmed death receptor 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) were not consistently expressed in the same direction in all tumors; however, the direction of expression change was the same in most immune cells. Although there is no well-established relationship between the expression of PD-1/PD-L1/CTLA-4 genes and the prognosis of patients with sarcomas, their interaction and extent of immune cell infiltration into sarcomas are probably the key determinants of therapeutic response. Our first pan-cancer study provides a relatively comprehensive understanding of immune checkpoint inhibitors in different sarcomas.

In modern maritime activities, the quality of ship communication directly impacts the safety, efficiency, and economic viability of ship operations. Therefore, predicting and analyzing ship communication status has become a crucial task to ensure the smooth operation of ships. Currently, ship communication status analysis heavily relies on large-scale, multi-source heterogeneous data with spatio-temporal and multi-modal features, which presents challenges for ship communication quality prediction tasks. To address this issue, this paper constructs a multi-modal spatio-temporal ontology and a multi-modal spatio-temporal knowledge graph for ship communication, guided by existing ontologies and domain knowledge. This approach effectively integrates multi-modal spatio-temporal data, providing support for subsequent efficient data analysis and applications. Taking the scenario of fishing vessel communication activities as an example, the query tasks for ship communication knowledge are successfully performed using a graph database, and we combine the spatio-temporal knowledge graph with graph convolutional neural network technology to achieve real-time communication quality prediction for fishing vessels, further validating the practical value of the multi-modal spatio-temporal knowledge graph.

Amphioxus species are considered living fossils and are important in the evolutionary study of chordates and vertebrates. To explore viral homologous sequences, a high-quality annotated genome of the Beihai amphioxus (Branchiostoma belcheri beihai) was examined using virus sequence queries. In this study, 347 homologous fragments (HFs) of viruses were identified in the genome of B. belcheri beihai, of which most were observed on 21 genome assembly scaffolds. HFs were preferentially located within protein-coding genes, particularly in their CDS regions and promoters. A range of amphioxus genes with a high frequency of HFs is proposed, including histone-related genes that are homologous to the Histone or Histone H2B domains of viruses. Together, this comprehensive analysis of viral HFs provides insights into the neglected role of viral integration in the evolution of amphioxus.