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Abstract Double-atom catalysts (DACs) have opened distinctive paradigms in the field of rapidly developing atomic catalysis owing to their great potential for promoting catalytic performance in various reaction systems. However, increasing the loading and extending the service life of metal active centres represents a considerable challenge for the efficient utilization of DACs. Here, we rationally design asymmetric nitrogen, sulfur-coordinated diatomic iron centres on highly defective nitrogen-doped carbon nanosheets (denoted A-Fe2S1N5/SNC, A: asymmetric), which possess the atomic configuration of the N2S1Fe-FeN3 moiety. The abundant defects and low-electronegativity heteroatoms in the carbon-based framework endow A-Fe2S1N5/SNC with a high loading of 6.72 wt%. Furthermore, A-Fe2S1N5/SNC has a low overpotential of 193 mV for the oxygen evolution reaction (OER) at 10 mA cm−2, outperforming commercial RuO2 catalysts. In addition, A-Fe2S1N5/SNC exhibits extraordinary stability, maintaining > 97% activity for over 2000 hours during the OER process. This work provides a practical scheme for simultaneously balancing the activity and stability of DACs towards electrocatalysis applications.

Abstract Background Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Abstract Background Peer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark. Method A parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects. Discussion The Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH. Trial registration Clinical registration number: ChiCTR2300077454.

Abstract Background Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. Method Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. Result We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. Conclusion This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming. Graphical abstract

Abstract Background Muscle-invasive bladder carcinoma (MIBC) is a serious and more advanced stage of bladder carcinoma. N6-Methyladenosine (m6A) is a dynamic and reversible modifications that primarily affects RNA stability and alternative splicing. The dysregulation of m6A in MIBC can be potential target for clinical interventions, but there have been limited studies on m6A modifications in MIBC and their associations with post-transcriptional regulatory processes. Methods Paired tumor and adjacent-normal tissues were obtained from three patients with MIBC following radical cystectomy. The additional paired tissues for validation were obtained from patients underwent transurethral resection. Utilizing Nanopore direct-RNA sequencing, we characterized the m6A RNA methylation landscape in MIBC, with a focus on identifying post-transcriptional events potentially affected by changes in m6A sites. This included an examination of differential transcript usage, polyadenylation signal sites, and variations in poly(A) tail length, providing insights into the broader impact of m6A alterations on RNA processing in MIBC. Results The prognostic-related m6A genes and m6A-risk model constructed by machine learning enables the stratification of high and low-risk patients with precision. A novel m6A modification site in the 3’ untranslated region (3’UTR) of IGLL5 gene were identified, characterized by a lower m6A methylation ratio, elongated poly(A) tails, and a notable bias in transcript usage. Furthermore, we discovered two particular transcripts, VWA1-203 and CEBPB-201. VWA1-203 displayed diminished m6A methylation levels, a truncated 3’UTR, and an elongated poly(A) tail, whereas CEBPB-201 showed opposite trends, highlighting the complex interplay between m6A modifications and RNA processing. Source code was provided on GitHub ( https://github.com/lelelililele/Nanopore-m6A-analysis ). Conclusions The state-of-the-art Nanopore direct-RNA sequencing and machine learning techniques enables comprehensive identification of m6A modification and provided insights into the potential post-transcriptional regulation mechanisms on the development and progression in MIBC.

Abstract N 6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)–real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF.

Predicting the Cooling Load (CL) of a building’s energy consumption is paramount in optimizing energy usage and mitigating environmental impacts. This study implemented a Decision Tree (DT) model to forecast the CL, aiming to optimize energy efficiency in building operations. To refine the predictive accuracy and generalization capability of the DT model, two advanced metaheuristic optimization algorithms were employed: the Giant Trevally Optimizer (GTO) and the Equilibrium Slime Mould Algorithm (ESMA). The algorithms were pivotal in hyperparameter tuning and model optimization, leading to enhanced performance metrics and more robust predictive outcomes. In this article, the models are evaluated using several metrics, including the Scatter Index (SI), Correlation Coefficient (R²), Mean Absolute Error (MAE), BIAS, and Root Mean Square Error (RMSE), where strong algorithm performance is determined by a high R² value and reduced model error is preferred with lower RMSE and MAE values. The findings yielded promising outcomes. The DTGT model, incorporating the GTO optimizer, exhibited remarkable performance, boasting an exceptional R2 value of 0.996, indicating a near-perfect alignment with the dataset. Moreover, the Root Mean Square Error (RMSE) value of 0.604 underscored the model’s exceptional precision in making predictions, with an impressively low error margin. These results underscore the resilience of the DTGT model as a useful instrument for exceptionally precise CL forecasts. Effective prediction of the CL leads to enhancing energy efficiency, reducing operational costs, and supporting smart building technologies by providing accurate.

Abstract Increasing the molecular weight while maintaining mono-dispersity has been proved crucial in innovating high-performance photovoltaic materials in giant oligomeric acceptors. However, developing efficient giant oligomeric donors to replace the batch-varied polymers remains challenging due to a lack of design principles. Here, by designing two unique isomeric rhodanine-based linkers, we successfully regulate the assembly behaviors of giant dimeric donors (G-Dimer-Ds) and fabricate the first all-giant-oligomer OSCs pairing with giant dimeric acceptor DY. Multiple characterizations demonstrate the small homo-molecular interaction with strong thermal-driven assembly capability in G-Dimer-D2 simultaneously facilitates reducing energetic disorder, improving charge transport and obtaining stable morphology, resulting in a satisfactory efficiency of 15.70% and long-term photostability with an extrapolated T 80 of ca.10,000 hours, and further enhancing thermal-driven assembly promotes efficiency of 16.05%. Our results provide construction approaches on efficient giant donors, and propose a promising type of OSC with completely definite structures, high efficiency and superior stability.

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

Abstract Fusarium oxysporum is an asexual filamentous fungus that causes vascular wilt in hundreds of crop plants and poses a threat to public health through Fusariosis. F. oxysporum f. sp. conglutinans strain Fo5176, originally isolated from Brassica oleracea, is pathogenic to Arabidopsis, making it a model pathosystem for dissecting the molecular mechanisms underlying host-pathogen interactions. Assembling the F. oxysporum genome is notoriously challenging due to the presence of repeat-rich accessory chromosomes. Here, we report a gap-free genome assembly of Fo5176 using PacBio HiFi and Hi-C data. The 69.56 Mb assembly contained 18 complete chromosomes, including all centromeres and most telomeres (20/36), representing the first gap-free genome sequence of a pathogenic F. oxysporum strain. In total, 21,460 protein-coding genes were annotated, a 26.3% increase compared to the most recent assembly. This high-quality reference genome for F. oxysporum f. sp. conglutinans Fo5176 provides a valuable resource for further research into fungal pathobiology and evolution.

Abstract Background Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by PNPLA2 gene mutations. Clinical manifestations are heterogeneous, and diagnosis is often delayed, usually gaining patients’ attention due to the increased risk of cardiomyopathy. Case presentation We herein report a 36-year-old Asian male presenting with progressive limb weakness, muscle atrophy of limbs and trunk, dysarthria, and heart failure. Electromyography indicated myogenic changes, and muscle biopsy results revealed characteristics of lipid storage myopathy. Genetic analysis of PNPLA2 revealed two heterozygous mutations: c.757 + 1G > T (chr11-823588, splice-5) on intron 6 and c.919delG (chr11-823854, p.A307Pfs*13) on exon 7. The patient improved limb strength, and dysarthria disappeared after the Medium Chain Fatty Acids diet. Conclusions In conclusion, we report for the first time that the two heterozygous mutations PNPLA2 c.919delG and c.757 + 1G > T together induced NLSDM, which was confirmed by muscle biopsy.

Abstract Background Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. Methods In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. Results GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. Conclusions Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.

Abstract Endothelial cells (ECs) are widely distributed in the human body and play crucial roles in the circulatory and immune systems. ECs dysfunction contributes to the progression of various chronic cardiovascular, renal, and metabolic diseases. As a key transcription factor in ECs, FLI-1 is involved in the differentiation, migration, proliferation, angiogenesis and blood coagulation of ECs. Imbalanced FLI-1 expression in ECs can lead to various diseases. Low FLI-1 expression leads to systemic sclerosis by promoting fibrosis and vascular lesions, to pulmonary arterial hypertension by promoting a local inflammatory state and vascular lesions, and to tumour metastasis by promoting the EndMT process. High FLI-1 expression leads to lupus nephritis by promoting a local inflammatory state. Therefore, FLI-1 in ECs may be a good target for the treatment of the abovementioned diseases. This comprehensive review provides the first overview of FLI-1-mediated regulation of ECs processes, with a focus on its influence on the abovementioned diseases and existing FLI-1-targeted drugs. A better understanding of the role of FLI-1 in ECs may facilitate the design of more effective targeted therapies for clinical applications, particularly for tumour treatment.

Abstract Background Fludarabine is a chemotherapeutic agent with lymphodepleting effects that is increasingly used as part of a conditioning regimen prior to allogeneic stem cell transplantation. Fludarabine is generally considered a relatively safe medication with only rare cases of cardiotoxic side effects. Case Presentation Here, we present a case of a 30-year-old woman who was undergoing conditioning for a haploidentical cell transplantation for treatment of Fanconi anemia with a 5-day course of daily fludarabine infusion. After her second fludarabine infusion, she was noted to have ectopic atrial bradycardia that resolved with supportive therapy and completion of fludarabine infusion. Conclusion We report the first case of ectopic atrial bradycardia associated with fludarabine. Although rare and transient, clinicians should recognize this rare cardiotoxic side effect of fludarabine.

Rainbow trout (Oncorhynchus mykiss) is one of the world's most widely farmed cold-water economic fish. It is also the primary cold-water fish species in China. Since the 1960s, the rainbow trout germplasm has been introduced from North Korea, the United States, Denmark, and other countries, and a systematic study has been carried out on germplasm preservation, identification, breeding, and variety breeding. Compared with rainbow trout diploid, the triploid has the advantages of a high feed conversion rate, fast growth rate, and good meat quality. Moreover, the triploid gonadal hypoplasia can mitigate risks associated with high mortality and meat quality decline during spawning and avert the ecological risk of invasive alien species caused by breeding escape. Therefore, breeding triploid rainbow trout has more significant market and ecological benefits. As diploid and triploid rainbow trout are very similar in terms of morphology, it is difficult to distinguish the ploidy of rainbow trout by morphology alone. Currently, DNA content analysis by flow cytometry is the main method used to identify the ploidy of rainbow trout, but this method necessitates the collection of fish blood or tissue samples, and the body length of the fish to collect the blood must be at least 5 cm. Additionally, these sampling operations may harm the fish. This method also involves a delicate operation, complicated technical process, and expensive consumables, thus, the popularization and application of triploid identification of rainbow trout are greatly restricted. Considering the limitations of the technical test for the ploidy of rainbow trout, a minimally invasive and economical method with only a small amount of sampling is needed to identify and analyze the ploidy of rainbow trout in batches. Microsatellite markers (SSR markers) are simple repeated sequences widely distributed in eukaryotic genomes and have been widely used in ploidy and pedigree analyses of fish. The advantages of microsatellite (SSR) analysis include high reproducibility, low sample requirements, and rapid population genetic analysis. In order to achieve the use of a minimally invasive method to collect samples for trout ploidy identification, this study analyzed 153 SSR markers using PCR amplification and electrophoresis separation technology. Among them, 139 SSR markers could be successfully amplified in diploid and triploid, and 132 SSR markers were screened for polymorphism. Finally, seven markers showed high variability in triploid. By verifying 52 reference samples with a known ploidy level and 48 samples with an unknown ploidy level, three SSR markers (SSR1054, SSR1056, and SSR1468) were further screened to distinguish the ploidy level. Moreover, three pairs of primer sequences with good stability were redesigned according to the three marker sequences for ploidy analysis application. When SSR markers were selected for ploidy identification, amplification sites with high variability were preferred because they greatly improve the efficiency of SSR-assisted ploidy identification. Differentiation of the variability of amplification sites mainly considers the number of alleles expressed and the relative frequency of these alleles. Furthermore, having clear map bands that are easy to observe and analyze is an important criterion for screening high-quality specific SSR markers. Statistical clear map bands can correctly judge the allelic configuration at each locus, thus, determining the ploidy level of rainbow trout. However, when the number of microsatellite DNA alleles shown in the electrophoretic map was less than the maximum number of alleles that may occur at the ploidy level of the polyploid species, it was difficult to accurately judge the ploidy by direct observation of the number of alleles. In diploid individuals, highly heterozygous SSR amplifies at most two alleles at a given site. Similarly, three and four alleles can be observed in triploid and tetraploid individuals, respectively. However, in some rare cases, the actual number of alleles cannot be correctly determined by looking directly at the number of alleles. For example, individuals with unknown ploidy show multiple possible genotypes for two alleles, which can occur with both diploids (AB) and triploids (AAB or ABB). Therefore, this study combined the analysis results of multiple specific SSR markers to improve the accuracy of ploidy detection. In addition, this study found three specific labeling bands that can assist in the differentiation of diploid and triploid rainbow trout, namely, SSR1054-305bp, SSR1056-463bp, and SSR1468-363bp. These three specific markers will greatly improve the accuracy of using SSR markers to identify triploid rainbow trout. Microsatellite null alleles are another potential limitation in SSR ploidy identification, which can be eliminated or avoided by changing the binding site of primers and flanking sequences due to the failure of normal gene amplification due to mutations in SSR lateral sequences. Although the results of this study cannot eliminate the presence of null alleles in future samples, the present experimental data suggest that the frequency of null alleles is so low that their impact on polyploid identification is minimal. SSR markers screened in this study solve the existing problems of a complex technical process and expensive consumables in the identification of rainbow trout ploidy, providing a minimally invasive, economical, reliable, and batch-operable molecular method and contributing to the study of the genetic diversity of rainbow trout with different ploidy.

In arid regions, the optimal utilization of river channels to collect rainwater resources can effectively alleviate the problem of water scarcity. This paper employs visual MODFLOW software to simulate the infiltration volume of rainwater under different schemes, with the objective of identifying the optimal infiltration volume. The results indicate that the infiltration volume of rainwater is 0.6, 79.7, 36.5, 62, and 10,000 m3 under different design schemes. COMSOL software is employed to simulate the infiltration situation of rainwater under different schemes, and the scheme with the most favourable infiltration effect is identified. The simulation results indicate that scenarios 2, 4, and 5 demonstrate superior early-stage infiltration performance. Ultimately, the optimal infiltration scheme is selected by integrating the infiltration volume, infiltration effect, construction, economic, and ecological factors to achieve the objective of enhancing rainwater harvesting and utilization. This study offers effective and reasonable measures for addressing the challenge of water resources management in arid regions. It provides suitable reference schemes for river channel rainwater storage projects and offers innovative approaches to rainwater resource utilization, thereby contributing to the alleviation of water scarcity in arid areas.

Abstract Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.

When 2-chloro-6-(trichloromethyl) pyridine (nitrapyrin) is applied alone, it typically does not significantly increase crop yield. Therefore, we combined gamma-aminobutyric acid (GABA) with nitrapyrin to address the limitations of nitrapyrin in enhancing yield. We conducted indoor incubation experiments and pot experiments in Chernozem and Calcic Kastanozem, respectively. The results demonstrated that GABA exerted an influence on the effectiveness of nitrapyrin by altering its degradation rate. In Chernozem, GABA accelerated nitrapyrin degradation, whereas, in Calcic Kastanozem, the results were the opposite. The pot experiment results showed that the combination of nitrapyrin and GABA increased rice total biomass by 5%, grain yield by 18 ± 2%, and plant nitrogen (N) uptake by 9 ± 1% compared to nitrapyrin applied alone. The increase in yield was attributed to the combined effect of nitrapyrin and GABA, which elevated root biomass and leaf area. In contrast, the effect of GABA on yield through altering the degradation rate of nitrapyrin was weaker. Therefore, the combination of nitrapyrin and GABA combined with urea increases rice yields in Chernozem and Calcic Kastanozem. The aim of this endeavour was to foster the development of a novel fertiliser product that offers both favourable agronomic outcomes and environmental benefits.

Abstract Aphids cause enormous financial losses to various crop plants on a global scale. Moreover, aphids are vectors for many plant viral diseases that can further hasten crop yield losses. Aphids secrete saliva during feeding that contains effectors that can regulate plants' defense responses and their underlying mechanisms. Although much research has been undertaken to determine the mechanisms contributing to plant-aphid interactions, our understanding of defense mechanisms against aphids is insufficient. The presence of piercing-sucking mouthparts in aphids makes the identification of aphid resistance more challenging, hindering our understanding of the mechanisms of plant resistance to aphids. In this article, we consolidate and assess the evidence that is currently available on plant-aphid interactions, address the gaps in our understanding, and propose new research directions. As an outcome, we present an in-depth review of the molecular mechanisms of aphid resistance in crops from five perspectives: physical protection against aphids using volatile compounds, PAMP-triggered immunity (PTI), effector-triggered immunity (ETI), plant hormone signaling and the inheritance of induced resistance through epigenetics.

Objective To observe the effect of deglycerolized red blood cells suspended in MAP on preservation and explore the most effective preservation method. Methods Concentrated red blood cells were prepared by centrifuging 400 mL of whole blood on the third day after collection. 40% compound glycerol solution was added using the ACP 215 automatic blood cell analyzer, and the resulting mixture was stored in an ultra-low temperature refrigerator at -65℃ for 30 days. After thawing and washing, it was equally separated into two bags. The control group received 0.9% sodium chloride solution, while the experimental group received MAP. Both groups were stored at 2-6℃. Hematological parameters, hemolysis indexes and cell metabolism indexes were measured on day 0, 1, 3, 5, 7 and 14 after storage. The quality changes of both groups were observed during the 14-day storage period. Results The quality of red blood cells in both groups was assessed through a panel of quality tests, including volume, hemoglobin content, free hemoglobin content, white blood cell residue, glycerin residue and sterility. These results met the Quality Requirements outlined in the "Quality Requirements of Whole Blood and Component Blood" (GB18469-2012), Hematocrit, red blood cell count, Hb recovery rate after washing and MCV meet the detection limit outlined in the "Expert Consensus on Quality Evaluation Indicators for Frozen Red Blood Cells", and the residual amount of platelets exceeds the detection limit(≤1%). There were no significant differences in RBC, Hct, MCV and hemoglobin between the two groups during the 14 day storage period. The level of free hemoglobin, hemolysis rate and K+ value increased in both groups over time. Significant differences in free hemoglobin were found on day 3, 5, 7 and 14 between the two groups(P

Abstract Background Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology. Methods On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers. Results As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences. Conclusions Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.

Abstract Determination of protein–ligand binding affinity (PLA) is a key technological tool in hit discovery and lead optimization, which is critical to the drug development process. PLA can be determined directly by experimental methods, but it is time-consuming and costly. In recent years, deep learning has been widely applied to PLA prediction, the key of which lies in the comprehensive and accurate representation of proteins and ligands. In this study, we proposed a multi-modal deep learning model based on the early fusion strategy, called DeepLIP, to improve PLA prediction by integrating multi-level information, and further used it for virtual screening of extracellular signal-regulated protein kinase 2 (ERK2), an ideal target for cancer treatment. Experimental results from model evaluation showed that DeepLIP achieved superior performance compared to state-of-the-art methods on the widely used benchmark dataset. In addition, by combining previously developed machine learning models and molecular dynamics simulation, we screened three novel hits from a drug-like natural product library. These compounds not only had favorable physicochemical properties, but also bound stably to the target protein. We believe they have the potential to serve as starting molecules for the development of ERK2 inhibitors.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age. The syndrome is characterized by androgen excess, ovarian dysfunction, insulin resistance (IR) and obesity, with an elevated risk of developing long-term complications, including cardiovascular disease and type 2 diabetes mellitus (T2D). The gut microbiota plays a role in the pathogenesis of PCOS by influencing the host's endocrine, metabolic and inflammatory state, as well as the gut-brain axis. Gut microbiota-derived extracellular vesicles (GMEVs) are lipid bilayer nanoparticles secreted by the gut microbiota and contain a variety of components, including proteins, lipids and nucleic acids. They serve as signaling molecules, facilitating bacterial-bacterial and bacterial-host communications. Bacterial extracellular vesicles (BEVs) affect host cells through the delivery of bioactive substances and physical interaction through membrane components, thereby participating in the regulation of metabolic, immune, and other cellular processes. Furthermore, BEVs, which are distinguished by low toxicity, high biocompatibility and stability, and the capacity to cross biological barriers, present a promising avenue for the development of novel drug delivery systems. The isolation and characterization of BEVs also facilitate the investigation of disease-specific biomarkers. Consequently, BEVs have immense potential for a range of medical research applications, including disease diagnosis and treatment. This article discusses the potential therapeutic effects and mechanisms of GMEVs in the treatment of PCOS.

Background Esophageal Squamous Cell Carcinoma (ESCC) poses a significant health challenge in China due to its high incidence and mortality. Single-cell transcriptomics has transformed the approach to cancer research, allowing detailed analysis of cellular and molecular heterogeneity. The interaction between the transcription factor STAT1 and the tumor suppressor LHPP is crucial, potentially influencing cancer progression and therapeutic outcomes. Objective This study aims to explore the molecular mechanisms and cellular dynamics underlying ESCC, with a focus on the role of transcription factors, particularly STAT1, and its regulatory relationship with LHPP, in the pathogenesis of ESCC. Methods Utilizing single-cell transcriptomics data sourced from the public database GEO (GSE160269), we identified major cell types and their transcriptomic changes in ESCC patients. Differential gene expression profiles were examined to understand the dynamics of the tumor microenvironment (TME). A cohort of 21 ESCC patients was recruited to validate the findings. Furthermore, in ESCC cell lines, we validated the transcriptional regulatory relationship between STAT1 and LHPP. Results Our analysis identified six major cell types within the ESCC microenvironment, revealing significant changes in cellular composition and gene expression profiles associated with tumorigenesis. Notably, a novel association between STAT1's regulatory role over LHPP was observed, suggesting a complex regulatory loop in ESCC pathogenesis. Elevated STAT1 and reduced LHPP expression were confirmed in patient samples with STAT1 negatively regulates LHPP expression at the promoter level; when the promoter binding motif regions were mutated, the transcriptional repression ability on LHPP was weakened. Conclusion The study highlights STAT1 as a core regulator in ESCC, directly influencing LHPP expression. The findings offer novel insights into the molecular mechanisms driving ESCC, shedding light on the cellular alterations and gene regulation dynamics within the ESCC microenvironment. This research provides a foundation for developing targeted therapeutic strategies, potentially utilizing the STAT1-LHPP axis as a focal point in ESCC treatment and prognosis.

Using molecular dynamics simulation with reactive force-field (ReaxFF), we study the reactive oxygen species (ROS)-mediated damage to the core domain of human immunodeficiency virus (HIV) integrase. Our results demonstrate that with the increase in the ROS concentration, the structure of the core domain of HIV is more severely damaged, including dehydrogenation, increasing oxygen-containing groups, shorting or damaging spirals, and breaking peptide bonds. We particularly note that ROS has a significantly higher capability to abstract H atoms from N atoms than C atoms. The effects of different species of ROS on dehydrogenation and shorting or damaging spirals are not prominent. In contrast, for increasing oxygen-containing groups and breaking peptide bonds, the effect of O is more remarkable than O3 and O3 is greater than ·OH. Moreover, carboxyl dehydrogenation and nitrogen dehydrogenation are more easily dehydrogenated, resulting in higher dehydrogenation ratios for polar amino acid residues. These meticulous findings deepen our understanding of the role of ROS in regulating the structure and function of the core domain of HIV integrase and provide valuable insights into the plasma treatment of acquired immune deficiency syndrome.

Phthalic acid esters (PAEs) are often added to plastics to enhance elasticity, transparency, durability and prolong service life as a kind of plasticizer. However, they are not chemically bonded to polymers and are difficult to degrade, which makes it easy for them to release into the environment and enter the human body from various potential sources. This results in environmental pollution and poses health risks. In order to protect ecosystem, ensure food safety and prevent disease, there is an urgent need for sensors that can achieve point-of-care detection of PAEs. Optical sensors have advantages of simplicity, portability and low cost, and have been widely applied to the detection of PAEs. In this review, we focus on introducing the recent advancements and trends in optical sensors for detection of PAEs represented by colorimetric (CL) sensors, fluorescence (FL) sensors and surface-enhanced Raman scattering (SERS) platform. Based on recognition strategies (e.g., label-free, aptamer, molecularly imprinted polymer, antibody and enzyme), the significant achievements of these optical sensors in the past 5 years are systematically classified and described in detail. Researchers can quickly know the development status of optical sensors for detection of PAEs in the past 5 years. This review highlights the strengths of each sensor type while also identifying their application limitations, providing researchers with valuable insights into future directions for optical sensor research.

Background: Lianling Tang (LLT), a traditional Chinese herbal decoction, is utilized for managing inflammatory skin conditions in China. This study explores the therapeutic effects and molecular mechanisms of LLT on atopic dermatitis (AD) in a mouse model, employing proteomics techniques. Methods: We evaluated the therapeutic efficacy of LLT on AD in mice by assessing skin inflammation scores, conducting histopathological examinations, and measuring serum levels of IgE, IL-4, and IL-6. Using Tandem Mass Tag (TMT) technology, we performed proteomics analysis of skin samples from Control, Model, LLT-treated, and positive control drug-treated mice, and identified differentially expressed proteins (DEPs). These proteins were then analyzed via GO and KEGG pathways to elucidate LLT's mechanisms in treating AD. Results: LLT markedly reduced skin inflammation scores, epidermal thickening, and mast cell infiltration, and decreased serum IgE, IL-4, and IL-6 levels in AD model mice, highlighting its therapeutic potential. Proteomics analysis identified Staphylococcus aureus infection as a pivotal AD pathogenesis mechanism and revealed critical proteins such as C1QA, C4B, C5, and FCGR3. LLT's mechanisms, such as modulating the complement activation, and influencing phagocytosis, effectively reduce inflammation and alleviate symptoms caused by Staphylococcus aureus in AD. Conclusion: LLT shows potential in AD treatment by modulating pathways associated with Staphylococcus aureus infection, effectively alleviating symptoms.

Studies have demonstrated the protective effect of milk fat globule membrane (MFGM) on probiotics in harsh environments. However, currently, there are no reports on the encapsulation of probiotics using MFGM. In this study, MFGM and pullulan (PUL) polysaccharide fibers were prepared by electrostatic spinning and used to encapsulate probiotics, with whey protein isolates (WPI)/PUL as the control. The morphology, physical properties, mechanical properties, survival, and stability of the encapsulated Lacticaseibacillus rhamnosus GG (LGG) were studied. The results showed that the MFGM/PUL solution had significant effects on pH, viscosity, conductivity, and stability. Electrostatic spinning improved the mechanical properties and encapsulation ability of the polymer formed by MFGM/PUL. LGG encapsulated in MFGM/PUL nanofibers survived rate was higher than WPI/PUL nanofibers in mimic intestinal juice, which could be attributed to the phospholipid content contained in MFGM. These results demonstrate that MFGM is a promising material for probiotic encapsulation, providing an important basis for the potential use of MFGM/PUL nanofibers as a robust encapsulation matrix.

Background: In the early stages of diabetic kidney disease (DKD), the pathogenesis involves abnormal angiogenesis in the glomerulus. Hirudin, as a natural specific inhibitor of thrombin, has been shown in previous studies to inhibit the migration of various tumor endothelial cells and abnormal angiogenesis. However, its role in DKD remains unclear. Methods: The effects of hirudin in DKD were studied using spontaneous type 2 diabetic db/db mice (which develop kidney damage at 8 weeks). Network pharmacology was utilized to identify relevant targets. An in vitro high glucose model was established using mouse glomerular endothelial cells (MGECs) to investigate the effects of hirudin on the migration and angiogenic capacity of MGECs. Results: Hirudin can ameliorate kidney damage in db/db mice. Network pharmacology suggests its potential association with the VEGFA/VEGFR2 pathway. Western blot and immunohistochemistry demonstrated elevated protein expression levels of VEGFA, VEGFR2, AQP1, and CD31 in db/db mice, while hirudin treatment reduced their expression. In the MGECs high glucose model, hirudin may reverse the enhanced migration and angiogenic capacity of MGECs in a high glucose environment by altering the expression of VEGFA, VEGFR2, AQP1, and CD31. Moreover, the drug effect gradually increases with higher concentrations of hirudin. Conclusions: This study suggests that hirudin can improve early-stage diabetic kidney disease kidney damage by inhibiting the migration and angiogenesis of glomerular endothelial cells, thereby further expanding the application scope of hirudin. Additionally, the study found increased expression of AQP1 in DKD, providing a new perspective for further research on the potential pathogenesis of DKD.

BackgroundThe Objective Structured Clinical Examination (OSCE) is a pivotal tool for assessing health care professionals and plays an integral role in medical education. ObjectiveThis study aims to map the bibliometric landscape of OSCE research, highlighting trends and key influencers. MethodsA comprehensive literature search was conducted for materials related to OSCE from January 2004 to December 2023, using the Web of Science Core Collection database. Bibliometric analysis and visualization were performed with VOSviewer and CiteSpace software tools. ResultsOur analysis indicates a consistent increase in OSCE-related publications over the study period, with a notable surge after 2019, culminating in a peak of activity in 2021. The United States emerged as a significant contributor, responsible for 30.86% (1626/5268) of total publications and amassing 44,051 citations. Coauthorship network analysis highlighted robust collaborations, particularly between the United States and the United Kingdom. Leading journals in this domain—BMC Medical Education, Medical Education, Academic Medicine, and Medical Teacher—featured the highest volume of papers, while The Lancet garnered substantial citations, reflecting its high impact factor (to be verified for accuracy). Prominent authors in the field include Sondra Zabar, Debra Pugh, Timothy J Wood, and Susan Humphrey-Murto, with Ronaldo M Harden, Brian D Hodges, and George E Miller being the most cited. The analysis of key research terms revealed a focus on “education,” “performance,” “competence,” and “skills,” indicating these are central themes in OSCE research. ConclusionsThe study underscores a dynamic expansion in OSCE research and international collaboration, spotlighting influential countries, institutions, authors, and journals. These elements are instrumental in steering the evolution of medical education assessment practices and suggest a trajectory for future research endeavors. Future work should consider the implications of these findings for medical education and the potential areas for further investigation, particularly in underrepresented regions or emerging competencies in health care training.

Introduction Metabolic dysfunction associated fatty liver disease (MAFLD) is a prevalent condition in patients with type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Although ISM1 has been shown to be associated with T2DM, its role in patients with MAFLD and metabolic syndrome (MetS) remains insufficiently examined. This study aimed to investigate the relationship between serum ISM1 and MAFLD in patients with T2DM and the potential involvement of MetS in this association.Research design and methods A total of 250 participants were divided into four groups: 60 patients with T2DM and MAFLD, 60 with newly diagnosed T2DM, 60 with MAFLD, and 70 healthy controls. Serum ISM1 levels were measured using ELISA. The distribution of ISM1 concentration in the combined data was divided into quartiles, and the Cochran-Armitage trend test was performed to estimate the significant trends across increasing quartiles.Results Compared with the controls, patients with coexisting MAFLD, MetS, and T2DM exhibited significantly elevated serum ISM1 concentrations. Serum ISM1 levels in the overweight/obese group were also higher than those in the lean group. Serum ISM1 levels were positively correlated with body mass index (BMI), uric acid, alanine aminotransferase, aspartate aminotransferase, total cholesterol (TC), low-density lipoprotein cholesterol, fasting insulin, and homeostasis model assessment of insulin resistance and negatively associated with age and high-density lipoprotein cholesterol (HDL-C). BMI, TC, and HDL-C were independently associated with serum ISM1 concentration. The relative risks for MAFLD, T2DM, and T2DM with MAFLD increased significantly with higher ISM1 quartiles. Furthermore, a positive correlation was observed between serum ISM1 levels and the number of MetS components, with the elevated plasma levels of ISM1 escalating the risk of developing MetS to some extent.Conclusions The combination of ISM1 with TG and UA was identified as the best predictive factor for diagnosing MAFLD and MetS, potentially due to their contribution to aggravating the metabolic state.

Recombinant adeno-associated virus (rAAV)-based gene therapies are expanding in their application. Despite progress in manufacturing, current analytical methods for product quantification and characterization remain largely unchanged. Although critical for product and process development, in-process testing, and batch release, current analytical methods are labor-intensive, costly, and hampered by extended turnaround times and low throughput. The field requires more efficient, cost-effective analytical techniques capable of handling large sample quantities to accelerate product and process development. Here, we evaluated Stunner from Unchained Labs for quantifying and characterizing rAAVs and compared it with established analytical methods. Stunner is a combinatorial analytic technology platform that interpolates ultraviolet-visible (UV-Vis) absorption with static and dynamic light scattering (SLS/DLS) analysis to determine capsid and genomic titer, empty and full capsid ratio, and assess vector size and polydispersity. The platform offers empirical measurements with minimal sample requirements. Upon testing hundreds of rAAV vectors, comprising various serotypes and transgenes, the data show a strong correlation with established analytical methods and exhibit high reproducibility and repeatability. Some analyses can be applied to in-process samples from different purification stages and processes, fulfilling the demand for rapid, high-throughput analysis during development. In sum, the pipeline presented streamlines small- and large-batch analytics.

Abstract Background As artificial intelligence (AI) increasingly integrates into medical education, its specific impact on the development of clinical skills among pediatric trainees needs detailed investigation. Pediatric training presents unique challenges which AI tools like ChatGPT may be well-suited to address. Objective This study evaluates the effectiveness of ChatGPT-assisted instruction versus traditional teaching methods on pediatric trainees’ clinical skills performance. Methods A cohort of pediatric trainees (n = 77) was randomly assigned to two groups; one underwent ChatGPT-assisted training, while the other received conventional instruction over a period of two weeks. Performance was assessed using theoretical knowledge exams and Mini-Clinical Evaluation Exercises (Mini-CEX), with particular attention to professional conduct, clinical judgment, patient communication, and overall clinical skills. Trainees’ acceptance and satisfaction with the AI-assisted method were evaluated through a structured survey. Results Both groups performed similarly in theoretical exams, indicating no significant difference (p > 0.05). However, the ChatGPT-assisted group showed a statistically significant improvement in Mini-CEX scores (p

Abstract Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.

Abstract Background Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life’s Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life’s essential 8 scores, and migraine. Methods 332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence. Results During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively. Conclusion Our study provides evidence that poor Healthy lifestyle and Life’s Essential 8 are associated with higher risk of new-onset migraine.

Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Drought, excessive use of nitrogen fertilizer, and decline in soil organic matter threaten corn production. This study investigated the potential of water retaining agents, inhibitors, and corn stalks in enhancing soil physicochemical properties to bolster corn yield in semi-arid farmlands. In our study, polyacrylamide addition increased the content of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) in the seedling stage, exchangeable potassium (K) in the mature stage but decreased the content of available phosphorus (P) in the seedling stage. Potassium polyacrylate addition increased the content of NH4+-N and decreased the content of available P in the seedling stage. The addition of inhibitors decreased the content of NH4+-N and available P in the seedling stage, NO3--N and available P in the jointing stage, and NH4+-N in the mature stage, respectively. Corn stalks returning could maintain soil moisture, decrease the content of NH4+-N in the seedling stage and exchangeable K in the mature stage, and increase the content of available P and exchangeable K in the seedling stage. Combined application of inhibitors and corn stalks could increase soil organic carbon (SOC) and ensure corn yield, which was the best fertilization mode in semi-arid cropland.

This is an article in the field of process mineralogy. The occurrence of zinc, associated dispersed elements Ga and Ge and the distribution characteristics of the main carrier minerals of a zinc ore in China are studied in detail by means of chemical analysis, microscope analysis and MLA mineral automatic quantitative technology.The results indicate that the zinc ore contains Zn 4.87%, Ga 4.10 g/t and Ge 59.00 g/t, no independent minerals of dispersed elements Ga and Geare found, Ga and Ge mainly occur in sphalerite. The theoretical recovery of Zn, Ga and Ge from sphalerite (including hemimorphite) are about 95%, 56% and 93% respectively. A small part of colloidal and fine grained sphalerite is difficult to obtain dissociation and easy to be lost in tailings, which has a certain effect on the recovery of zinc.

Abstract Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

Abstract Background The development of antiretroviral therapy broadly extends the life expectancy of persons living with HIV (PLHIV). However, stigma and discrimination are still great threat to these individuals and the world's public health care system. Accurate and reproducible measures are prerequisites for robust results. Therefore, it is essential to choose an acceptable measure with satisfactory psychometric properties to assess stigma and discrimination. There has been no systematic review of different stigma and discrimination tools in the field of HIV care. Researchers and clinical practitioners do not have a solid reference for selecting stigma and discrimination measurement tools. Methods We systematically searched English and Chinese databases, including PubMed, EMBASE, CINAHL, Web of Science, PsycINFO, ProQuest Dissertations and Theses, The Cochrane Library, CNKI,, and Wanfang, to obtain literature about stigma and discrimination measurement tools that have been developed and applied in the field of HIV. The search period was from 1st January, 1996 to 22nd November 2021. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline (2018 version) was applied to assess the risk of bias for each involved study and summarize the psychometric properties of each tool. The modified version of the Grading of Recommendations Assessment, Development, and, Evaluation (GRADE) method was used to grade the evidence and develop recommendations. Results We included 45 studies and 19 PROMs for HIV/AIDS-related stigma and discrimination among PLHIV. All studies had sufficient methodological quality in content validity, structural validity, internal consistency, and the hypothesis testing of structural validity. Limited evidence was found for cross-cultural validity, stability, and criterion validity. No relevant evidence was found concerning measurement error and responsiveness. The Internalized AIDS-related Stigma Scale (IARSS), Internalized HIV Stigma Scale (IHSS), and Wright's HIV stigma scale (WHSS) are recommended for use. Conclusions This study recommends three PROMs for different stigma and discrimination scenarios, including IARSS for its good quality and convenience, IHSS for its broader range of items, higher sensitivity, and greater precision, and WHSS for its comprehensive and quick screening. Researchers should also consider the relevance and feasibility of the measurements before putting them into practice. Systematic review registration PROSPERO CRD42022308579

Abstract Background To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. Methods We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). Results We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819–0.928) and 0.772 (95% CI: 0.699–0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P

There are many studies about flexible job shop scheduling problem with fuzzy processing time and deteriorating scheduling, but most scholars neglect the connection between them, which means the purpose of both models is to simulate a more realistic factory environment. From this perspective, the solutions can be more precise and practical if both issues are considered simultaneously. Therefore, the deterioration effect is treated as a part of the fuzzy job shop scheduling problem in this paper, which means the linear increase of a certain processing time is transformed into an internal linear shift of a triangle fuzzy processing time. Apart from that, many other contributions can be stated as follows. A new algorithm called reinforcement learning based biased bi-population evolutionary algorithm (RB2EA) is proposed, which utilizes Q-learning algorithm to adjust the size of the two populations and the interaction frequency according to the quality of population. A local enhancement method which combimes multiple local search stratgies is presented. An interaction mechanism is designed to promote the convergence of the bi-population. Extensive experiments are designed to evaluate the efficacy of RB2EA, and the conclusion can be drew that RB2EA is able to solve energy-efficient fuzzy flexible job shop scheduling problem with deteriorating jobs (EFFJSPD) efficiently.

Abstract Background Understanding cancer patients’ unmet needs for chemotherapy-related symptom management will assist clinicians in developing tailored intervention programs. Little is known about the association between perceived communication efficacy and unmet care needs for symptom management in patients with lung and colorectal cancer. Objectives To examine the unmet care needs for symptom management of patients with lung and colorectal cancer and their association with perceived communication efficacy. Methods A cross-sectional survey was conducted in a tertiary hospital in China from July to November 2020. A convenience sample of 203 patients with lung and colorectal cancer undergoing chemotherapy completed survey questionnaires, including the MD Anderson Symptom Inventory Scale and the Perceived Efficacy in Patient‒Physician Interactions Scale. Results Approximately 43% of participants had at least one symptom with unmet needs. Fatigue was reported as the symptom with the highest occurrence (66%), the highest demand for supportive care (36%), and the highest prevalence of unmet needs (19%). Low levels of perceived communication efficacy independently predicted participants’ unmet needs for symptom management (β=-0.13, p = 0.011). Conclusions This study highlights the necessity of introducing clinical assessment tools and guidelines to address fatigue and other chemotherapy-induced symptoms in patients with lung and colorectal cancer. Clinical programs designed to actively engage cancer patients to voice their needs and strengthen their communication efficacy are also warranted.

CdS nanospheres were grown on indium tin oxide (ITO) substrate using a hydrothermal method. The crystal structure, morphology and electronic structure of the samples synthesized were characterized in detail. The results confirm that the crystallinity, size, crystal defects of the CdS nanospheres and the film thickness of CdS photoelectrodes can be tuned by varying the precursor Cd2+ concentration. Combined with charge transfer dynamics analysis, it can be found that proper particle size and film thickness, as well as fewer defects, will result in better charge separation efficiency of the prepared CdS/ITO photoelectrodes, thereby exhibiting better photoelectrochemical performance for water splitting. The optimized CdS/ITO photoelectrode synthesized with a Cd2+ concentration of 0.14 mol·L−1 gave a photocurrent density of 5.10 mA·cm−2 at potential of 1.23 V versus the reversible hydrogen electrode (RHE), under a simulated solar illumination of 100 mW·cm−2.

Straw return is commonly used to improve soil fertility and quality, thereby contributing to improved crop production; however, the influence of different straw management on soil moisture variation, its response to precipitation, and soil pore properties remains largely inadequate, let alone the relationships between these factors. To fill this knowledge gap, the temporal dynamics of soil moisture were monitored during the maize growing season from 2022 to 2023 in a fixed-site field experiment on straw return, including straw removal (CK), straw direct incorporation (SD) and straw-derived biochar incorporation (BC), in Northeast China. In contrast to CK, BC was observed to have a significant impact on soil moisture, increasing the monthly average of September by 30.3 % and the annual average by 5.90 % in 2022 (P < 0.05). In addition, SD significantly increased the average for June by 28.5 % (P < 0.05) and exhibited a more pronounced linear correlation between soil moisture and rainfall amount with the greatest slope (y = 0.2061x + 0.0026, R² = 0.3098). The results indicated that the soil water storage capacity was enhanced when straw was returned, with a more effective impact in BC in 2022 but in SD in 2023, partially attributing to the discrepancies in precipitation quantity, intensity, and frequency between the two years. Furthermore, BC significantly reduced the dissipated precipitation fraction and enhanced the soil water memory in both 2022 (P < 0.05) and 2023 (P < 0.01), based on the evaluation of the capacity of soil to retain water. The results of X-ray computed tomography (CT) scanning showed that straw return resulted in the reconstruction of a relatively intricate pore network, which was characterized by an increase in porosity and macropore number in SD, an increase in pore circularity, a reduction in pore diameter and maccropore number in BC, which was associated with soil layer depth. It is concluded that the improvement of soil water and pore properties, as evidenced by an enhanced soil moisture memory and an increased porosity, contributed to the enhancement of soil nutrients under straw return conditions. This study provides valuable insights for selecting a suitable mode of straw return, thereby facilitating the effective utilization of straw and water resources in agricultural systems, particularly in arid regions.

Background: Puerarin (Pue) is an isoflavone compound with significant therapeutic effect on cardiovascular diseases, but its poor water solubility and low oral bioavailability limit clinical application. Methods: In this study, Pue was prepared into PLGA nanoparticles (Pue-PLGA NPs) by emulsion solvent volatilization method. The morphology, particle size, Zeta potential, X-ray diffraction (XRD), and fourier transform infrared (FTIR) of the NPs were characterized. Additionally, their stability and in vitro release were evaluated. SD rats were orally administered wtih Pue and Pue-PLGA NPs, and a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to determine the concentration of blood samples and to investigate the pharmacokinetic behaviour of Pue and Pue-PLGA NPs in rats. Results: The NPs were observed by transmission electron microscopy (TEM) as regular spheroids and uniformly dispersed. The average particle size of the NPs was (167.1±5.26）nm, the Zeta potential was (-29.88±2.46)mV, the encapsulation rate was (83.12 %±4.73 %) and the drug loading capacity was (7.75 %±1.81 %). The results of in vitro release showed that the drug was released slowly and continuously from the NPs, reaching the release platform in 24 h, and the cumulative release amount was (88.55±2.86) %. The pharmacokinetic results showed that the AUC0–24, AUC0-∞, Cmax, Tmax, t1/2, MRT0–24 and MRT0-∞ of Pue-PLGA NPs were 2.196, 1.978, 1.327, 1.5, 1.385, 3.915 and 3.140 times of Pue, respectively. The relative bioavailability was (197.82±25.28) %. Conclusion: These results indicated that the prepared nanoparticles had small particle size, high encapsulation rate, drug loading capacity and good slow-release effect, and could significantly improve the oral bioavailability of Pue in rats.

Producing chemicals from alternative feedstocks such as biomass is promising route for sustainable manufacturing. In this study, we unravel the reaction mechanism and the nature of the active site for the dehydration of biobased lactic acid to acrylic acid through systematic in-situ diffuse reflectance infrared Fourier transform spectroscopic analysis. We demonstrated that the formation and the stability of lactate as the reaction intermediate on the catalyst surface is crucial to obtain high acrylic acid selectivity. The simultaneous presence of Lewis acid sites and stable lactate intermediates appear to be key in pushing the reaction equilibrium toward dehydration of lactic acid to acrylic acid. We suggest that lactate cannot be formed or is not stable in the presence of BrØnsted acid sites, resulting in low acrylic acid selectivity over HY catalysts. In addition, we have shown that alkali and alkaline-metal modification reduces the number of in-situ generated BrØnsted acid sites, promoting stable lactate intermediate formation and thus inhibiting side reactions catalyzed by BrØnsted acidic sites.

This study aimed to investigate the correlation between ultrafiltration rate (UFR) and hemoglobin levels and erythropoietin (EPO) response in patients receiving maintenance hemodialysis (MHD). 225 MHD patients were divided into three groups according to the UFR: < 10 ml/h/kg, 10–13 ml/h/kg, and >13 ml/h/kg. Clinical parameters and prognosis were compared among the groups. Multiple linear correlation and regression analyses were conducted. SPSS 26.0 (IBM, Chicago, IL, USA) was used to analyze all statistics. The UFR < 10 ml/h/kg group was older than the other groups (p 13 ml/h/kg group had the highest SpKt/V (p