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Abstract Recent advancements in bacterial two-component systems (TCS) have spurred research into TCS-based biosensors, notably for their signal amplification and broad input responsiveness. The CusRS system in Escherichia coli (E. coli), comprising cusS and cusR genes, is a copper-sensing module in E. coli. However, due to insufficient sensing performance, CusRS-based biosensors often cannot meet practical requirements. To address this issue, we made improvements and innovation from several aspects. CusR and CusS expression were adjusted to enhance the Cu(II) biosensor’s performance. A copy-number inducible plasmid was used for signal amplification, while removing copper detox genes cueO and cusCFBA improved sensitivity and lowered detection limits. Ultimately, in the optimized biosensor of Cu26, the fold-change (I/I0) increased from 1.5-fold to 18-fold at 1 μM, rising to 100-fold after optimizing the cell culture procedure. The biosensor’s high fluorescence enabled rapid, instrument-free detection and an improved analysis strategy reduced the detection limit to 0.01 μM, surpassing traditional methods.

Abstract Background Traditionally, poverty assessment has relied on a single income criterion, which is inadequate in contexts where absolute poverty has been mitigated. This study developed a weighting scheme for the Multidimensional Health Poverty Index (MHPI) based on sustainable livelihood framework (SLF), aimed at enhancing the accuracy of poverty identification in China. Methods A two-round Delphi process was used to determine the indicators of the index system. The weight of each indicator was calculated using the analytic hierarchy process (AHP) method. The multidimensional poverty index incorporates SLF’s five dimensions: financial, natural, physical, social, and human capital. Results The initial 46 indicators formed an indicator pool for the Delphi questionnaire. Based on the final consensus of the expert panel, the Delphi consultation resulted in an index system comprising six first-level and 23 second-level indicators. The weight values of the first-level indicators (economic security, health status, education, social capital, healthcare utilisation, and living conditions) were 0.2715, 0.2593, 0.0855, 0.0657, 0.1812, and 0.1363, respectively. Conclusion This study established a scientific and effective index to evaluate generate weight for estimating multidimensional health poverty in China. Economic security, health status, and healthcare utilisation are the most crucial aspects of multidimensional health poverty. Moreover, the results indicated that vocational training and social capital should be emphasised.

Abstract Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.

Abstract Background Colon cancer, a frequently encountered malignancy, exhibits a comparatively poor survival prognosis. Perineural invasion (PNI), highly correlated with tumor progression and metastasis, is a substantial effective predictor of stage II-III colon cancer. Nonetheless, the lack of effective and facile predictive methodologies for detecting PNI prior operation in colon cancer remains a persistent challenge. Method Pre-operative computer tomography (CT) images and clinical data of patients diagnosed with stage II-III colon cancer between January 2015 and December 2023 were obtained from two sub-districts of Sun Yat-sen Memorial Hospital (SYSUMH). The LASSO/RF/PCA filters were used to screen radiomics features and LR/SVM models were utilized to construct radiomics model. A comprehensive model, shown as nomogram finally, combining with radiomics score and significant clinical features were developed and validated by area under the curve (AUC) and decision curve analysis (DCA). Result The total cohort, comprising 426 individuals, was randomly divided into a development cohort and a validation cohort as a 7:3 ratio. Radiomics scores were extracted from LASSO-SVM models with AUC of 0.898/0.726 in the development and validation cohorts, respectively. Significant clinical features (CA199, CA125, T-stage, and N-stage) were used to establish combining model with radiomics scores. The combined model exhibited superior reliability compared to single radiomics model in AUC value (0.792 vs. 0.726, p = 0.003) in validation cohorts. The radiomics-clinical model demonstrated an AUC of 0.918/0.792, a sensitivity of 0.907/0.813 and a specificity of 0.804/0.716 in the development and validation cohorts, respectively. Conclusion The study developed and validated a predictive nomogram model combining radiomics scores and clinical features, and showed good performance in predicting PNI pre-operation in stage II-III colon cancer patients.

Abstract Silicon carbide (SiC) MOSFETs are garnering widespread attention due to their superior performance in high‐temperature, high‐frequency, and high‐voltage applications, emerging as the preferred power semiconductor devices in converters for photovoltaic power generation and new energy vehicles. However, SiC MOSFETs are prone to gate drive and drain‐source voltage oscillations during high‐speed switching events, resulting in diminished system efficiency, increased electromagnetic interference, reduced device safety, and even compromising the overall reliability of the converter. This paper introduces an oscillation suppression method based on a gate LCR parallel branch, aimed at optimizing the switching performance of SiC MOSFETs. A half‐bridge circuit model based on SiC MOSFET is established, and the mechanism of gate and drain‐source oscillation is meticulously analysed using the transfer function expression. Building upon this, the LCR parallel branch parameters are meticulously designed to introduce appropriate damping in the gate drive path, effectively mitigating oscillations. Experimental results demonstrate that the proposed design not only significantly reduces the amplitude of oscillations but also shortens the switch‐transition time. This enhancement effectively increases the switching frequency and reduces switching losses.

Abstract Background Exposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury. Methods Two hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1β, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting. Results Cur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1β, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa. Conclusions Exposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

Abstract Policies to address climate change have been implemented worldwide in recent years. The core of these policies is to control greenhouse gas (GHG) emissions, which primarily stem from the consumption of fossil fuels. Consequently, the implementation of climate policies can affect other energy-related issues, such as energy poverty, a critical element of the UN Sustainable Development Goals (SDGs). This paper uses cross-country data from 2000 to 2020 to study the possible policy spillovers from climate actions to energy poverty. We show that a spillover effect does exist. In other words, a higher number of climate policies is associated with a lower level of energy poverty. The spillover is realized through improvements in energy efficiency, the promotion of renewable energy, and support for innovations. In addition, legislative policies are found to have stronger spillover effects. While the overall policy effects are positive for executive policies, regulations tend to have negative impacts on energy development. There is also evidence demonstrating heterogeneous effects between long-term and short-term policies, and between developed and developing countries. Discovering this spillover effect gives extra motivation for countries to adopt climate policies and actively seek synergies in achieving broader sustainable goals.

Abstract Background While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute‐on‐chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short‐term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short‐ and long‐term mortality in patients with ACLF. Methods This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3‐SMI). Subsequently, the patients were divided into sarcopenia and non‐sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short‐term (28 days) and long‐term (1 year and overall) mortality rates. Results A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28‐day, 1‐year and overall mortality rates in the sarcopenia group were significantly higher than those in the non‐sarcopenia group (37% vs. 22.3%, P

Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.

Health poverty, as a critical component of multidimensional poverty, plays a key role in the successful identification for the implementation of targeted poverty alleviation and health poverty alleviation policies by the state. This study aims to summarize and critique the existing literature on the definitions and logical deductions of the health poverty concept, refer to domestic and international multidimensional health poverty indices, and based on the current state of poverty in China, construct a poverty function model using the sustainable livelihood framework and Grossman′s health demand theory. In addition, the study outlines a multidimensional health poverty wheel applicable to Chinese residents. The research shows that China′s current poverty problems have evolved, and the "poverty-disease" vicious cycle is a central element hindering health poverty and poverty management in China. Therefore, accurately identifying the health-impoverished population and empirically measuring multidimensional health poverty are among the key elements in advancing the work of poverty alleviation and reduction.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Abstract Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Background: Fumonisins (FUMs) are among the most common mycotoxins in plant-derived food products. FUMs contamination has considerably impacted human and animal health, while causing significant economic losses. Hence, management of FUMs contamination in food production and supply chains is needed. The toxicities of FUMs have been widely investigated. FUMs management has been reported and several available strategies have been developed successfully to mitigate FUMs contamination present in foods. However, currently available management of FUMs contamination from different phases of food chains and the mechanisms of some major strategies are not comprehensively summarized. Aim of review: This review comprehensively characterize the occurrence, impacts, and management of FUMs contamination across food production and supply chains. Pre- and post-harvest strategies to prevent FUMs contamination also are reviewed, with an emphasis on the potential applications and the mechanisms of major mitigation strategies. The presence of modified FUMs products and their potential toxic effects are also considered. Importantly, the potential application of biotechnological approaches and emerging technologies are enunciated. Key scientific concepts of review: Currently available pre- and post-harvest management of FUMs contamination primarily involves prevention and decontamination. Prevention strategies are mainly based on limiting fungal growth and FUMs biosynthesis. Decontamination strategies are implemented through alkalization, hydrolysis, thermal or chemical transformation, and enzymatic or chemical degradation of FUMs. Concerns have been raised about toxicities of modified FUMs derivatives, which presents challenges for reducing FUMs contamination in foods with conventional methodologies. Integrated prevention and decontamination protocols are recommended to control FUMs contamination across entire value chains in developed countries. In developing countries, several other approaches, including cultivating, introducing Bt maize, simple sorting/cleaning, and dehulling, are suggested. Future studies should focus on biotechnological approaches, emerging technologies, and metagenomic/genomic identification of new degradation enzymes that could allow better opportunities to manage FUMs contamination in the entire food system.

ABSTRACT Abies nephrolepis Nature Reserve has complex habitats and rich species diversity but lacks systematic ecological surveys. We focused on Orchid in Abies nephrolepis Nature Reserve, investigated and analyzed Orchid diversity and changes in community structure according to the characteristics of the alpine valleys in the study area, in terms of altitude gradient and habitat type, using the sample line method and the quadrat method. The results showed that 11 genera and 13 species of Orchidaceae were found in the survey, among which the species richness of Malaxis monophyllos was the highest, Neottia puberula was the second highest, and the species richness of Tulotis ussuriensis was the lowest, and the species with relative plurality ≥ 10% were Malaxis monophyllos (51.69%), Neottia puberula (14.77%), and Cypripedium guttatum (11.15%). The results of diversity analysis showed that Orchidaceae species were rich and the diversity index were the highest in the middle altitude area of 1950–2250 m; the distribution of Orchidaceae in the low altitude area was obviously clustered, and the similarity with the high altitude area was low. With the increase in altitude, the number of species showed an increase and then a decrease, showing a single‐peak state, which was in line with the theory of “Intermediate altitude expansion hypothesis”. The species and number of Orchidaceae in different habitats of Abies nephrolepis Nature Reserve also varied considerably, with Shannon‐Wiener diversity index being the highest in EV4 (Abies nephrolepis + Picea meyeri + Picea wilsonii + Larix gmelinii var. principis‐rupprechtii—Lonicera hispida—Carex lanceolata community) and EV5, and the smallest in EV1 habitats, Pielow evenness index being the highest in EV5 habitats and the lowest in EV1 habitats, and Simpson's index being the highest in EV5 habitats and the lowest in EV1 habitats. This study provides a scientific basis for strengthening regional monitoring of species diversity and protecting biodiversity.

Cities constitute a critical component of the “dual carbon” strategy, highlighting the importance of examining the carbon emission trends within various city categories to formulate a low-carbon development path. In this paper, 21 cities (prefectures) in Sichuan province were divided into 4 categories (service-based cities, resource-based cities, industry-based cities, and other cities) through K-means clustering, and the differences in driving factors of carbon emissions in different types of cities were explored. At the same time, baseline scenarios, technological innovation scenarios, controlled development scenarios, and mandatory emission reduction scenarios were set up to dynamically simulate the evolution path of urban carbon emissions in the next 30 years from the bottom-up. The results show that: (1) Input scale is the main driving factor for carbon emission growth in Sichuan province, while input carbon intensity is the leading factor for carbon emission reduction. Environmental input and population scale have opposite effects on carbon emission of different urban types. (2) Resource-based cities face challenges in completing the phased goal of “carbon peaking” under both baseline scenarios and controlled development scenarios. These cities have gradually become the predominant city type of emission source in Sichuan province, surpassing service-based cities. (3) Except for the normal scenario, Sichuan province can achieve the target of “carbon peaking” in other scenarios, and is expected to achieve the target of 90 % greenhouse gas reduction by 2050. (4) Among the 81 development paths derived from the urban scenario combinations, the path labeled M−B−C−M exhibits the lowest economic-ecological comprehensive impact coefficient. The bottom-up carbon emission scenario analysis framework established in this paper offers a novel perspective for the study of “carbon peaking” and can provide theoretical support for policymakers in devising regional low-carbon development strategies.

Increasing carbon sequestration (CS) in soils and biomass is an important land-based solution in mitigating global warming. Ecosystems provide a wide range of ecosystem services (ESs). The necessity to augment CS may engender alterations in the interrelationships among ESs, thereby heightening the probability of ecosystem destabilization. This study developed a framework that integrates machine learning and interpretable predictions to evaluate the destabilization risk resulting from alterations in ecosystem service relationships dominated by CS. We selected Northeastern China as study area to estimate six ESs and identified areas of destabilization risk among the three services most relevant to CS, including food production (FP), soil retention (SR), and habitat quality (HQ). Subsequently, we compared three machine learning models (random forest, extreme gradient boosting, and support vector machine) and introduced the Shapley additive interpretation (SHAP) method for driving mechanism analysis. The results showed that: (1) CS-FP had 30.28% of its area at destabilization risk and is the most significant ecosystem service pair; (2) Heilongjiang Province was the region with the highest destabilization risk of CS, with CS-FP and CS-SR accounting for 44.76% and 52.89% of all regions, respectively; (3) a non-linear relationship and the presence of threshold features between socio-ecological factors and the prediction of destabilization risk. The study has potential practical value for destabilization risks prevention, while also providing a scientific basis for formulating comprehensive carbon management policies and maintaining ecosystem stability.

IntroductionThere are considerable similarities between the pathophysiology of gout flare and the dysregulated inflammatory response in severe COVID-19 infection. Monocytes are the key immune cells involved in the pathogenesis of both diseases. Therefore, it is critical to elucidate the molecular basis of the function of monocytes in gout and COVID-19 in order to develop more effective therapeutic approaches.MethodsThe single-cell RNA sequencing (scRNA-seq), large-scale genome-wide association studies (GWAS), and expression quantitative trait loci (eQTL) data of gout and severe COVID-19 were comprehensively analyzed. Cellular heterogeneity and intercellular communication were identified using the scRNA-seq datasets, and the monocyte-specific differentially expressed genes (DEGs) between COVID-19, gout and normal subjects were screened. In addition, the correlation of the DEGs with severe COVID-19 and gout flare was analyzed through GWAS statistics and eQTL data.ResultsThe scRNA-seq analysis exhibited that the proportion of classical monocytes was increased in both severe COVID-19 and gout patient groups compared to healthy controls. Differential expression analysis and MR analysis showed that NLRP3 was positively associated with the risk of severe COVID-19 and involved 11 SNPs, of which rs4925547 was not significantly co-localized. In contrast, IER3 was positively associated with the risk of gout and involved 9 SNPs, of which rs1264372 was significantly co-localized.DiscussionMonocytes have a complex role in gout flare and severe COVID-19, which underscores the potential mechanisms and clinical significance of the interaction between the two diseases.

Abstract Background Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. Methods This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Results Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Conclusions Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

As an essential crop that provides vegetable oil and protein, soybean (Glycine max (L.) Merr.) is widely planted all over the world. However, the scarcity of water resources worldwide has seriously impacted on the quality and yield of soybean. To address this, exploring excellent genes for improving drought resistance in soybean is crucial. In this study, we identified natural variations of GmFNSII-2 (flavone synthase II) significantly affect the drought resistance of soybeans. Through sequence analysis of GmFNSII-2 in 632 cultivated and 44 wild soybeans nine haplotypes were identified. The full-length allele GmFNSII-2C, but not the truncated allele GmFNSII-2A possessing a nonsense nucleotide variation, increased enzyme activity. Further research found that GmDREB3, known to increase soybean drought resistance, bound to the promoter region of GmFNSII-2C. GmDREB3 positively regulated the expression of GmFNSII-2C, increased flavone synthase abundance and improved the drought resistance. Furthermore, a single-base mutation in the GmFNSII-2C promoter generated an additional drought response element (CCCCT), which had stronger interaction strength with GmDREB3 and increased its transcriptional activity under drought conditions. The frequency of drought-resistant soybean varieties with Hap 1 (Pro:GmFNSII-2C) has increased, suggesting that this haplotype may be selected during soybean breeding. In summary, GmFNSII-2C could be used for molecular breeding of drought-tolerant soybean.

Abstract Background Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. Conclusions Our study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.

Metastasis is the main manifestation of advanced gastric cancer patients and the main cause of treatment failure.Some gastric cancer metastasis related factors promote or inhibit gastric cancer metastasis by regulating epithelial-mesenchymal transition, adhesion, migration, invasion, proliferation and angiogenesis.This article aims to provide a view of the effects and potential molecular mechanisms of gastric cancer metastasis related factors in different stages of gastric cancer metastasis, clarify their mechanisms of regulating gastric cancer metastasis and potential therapeutic targets, provide new detection methods for gastric cancer metastasis and new treatment options for patients with metastasis gastric cancer.

To meet the goal of worldwide decarbonization, the transformation process toward clean and green energy structures has accelerated. In this context, coal-fired power plant (CFPP) and large-scale energy storage represented by compressed air energy storage (CAES) technology, are tasked with increasing renewable resource accommodation and maintaining the power system security. To achieve this, this paper proposes the concept of a CFPP–CAES combined cycle and a trigenerative system based on that. Considering the working conditions of the CFPP, thermal characteristics of three typical operation modes were studied and some general regularities were identified. The results of various potential integration schemes discussion indicated that extracting water from low-temperature points in the feedwater system to cool pressurized air and simultaneously increase the backwater temperature is beneficial for improving performance. In addition, preheating the pressurized air before the air expanders via low-grade water in the feedwater system as much as possible and reducing extracted steam contribute to increasing the efficiency. With the optimal integration scheme, 2.85 tonnes of coal can be saved per cycle and the round-trip efficiency can be increased by 2.24%. Through the cogeneration of heat and power, the system efficiency can reach 77.5%. In addition, the contribution degree of the three compression heat utilization methods to the performance improvement ranked from high to low, is preheating the feedwater before the boiler, supplying heat, and flowing into the CFPP feedwater system. In the cooling energy generation mode, the system efficiency can be increased to over 69%. Regardless of the operation mode, the benefit produced by integration is further enhanced when the CFPP operates at higher operating conditions because the coupling points parameters are changed. In addition, the dynamic payback period can be shortened by 11.33 years and the internal rate of return increases by 5.20% under a typical application scenario. Regarding the effect of different application scenarios in terms of economics, investing in the proposed system is more appropriate in regions with multiple energy demands, especially heating demand. These results demonstrate the technical advantages of the proposed system and provide guiding principles for its design, operation, and project investment.

Abstract Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P

Abstract The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Abstract Background Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. Results Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. Conclusions The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.

Background Acute myeloid leukemia (AML) is a disease characterized by the proliferation of abnormal cells originating from blood stem cells. Understanding the pathogenesis and progression of AML, as well as identifying molecular markers for early diagnosis and prognosis assessment, is of paramount importance.Methods The AML dataset was obtained from the Cancer Genome Atlas (TCGA), while the normal sample dataset was derived from the Genotype-Tissue Expression(GTEx) dataset. Furthermore, the association between SRSF12 expression and drug response was assessed using the Cancer Therapeutic Response Portal (CTRP) database to evaluate its potential therapeutic value. Finally, SRSF12 expression in AML cells was measured using quantitative real-time PCR (qRT-PCR).Result The difference in SRSF12 expression between 13 types of tumors and normal tissue samples was found to be statistically significant (P

Objectives: Adverse childhood experiences (ACEs) are associated with frailty, while the association with frailty state transitions and the role of social participation remain unclear. This study aimed to investigate the association between ACEs and frailty state transitions, alongside the moderating effect of social participation Methods: Data from 9,621 adults aged 45 and older from the China Health and Retirement Longitudinal Study (2011–2020) were analyzed. Frailty was measured with the frailty index, while ACEs and social participation were measured with a validated questionnaire. The association between ACEs and frailty state transitions was estimated using multi-state models. An interaction analysis were used to examine the moderating effects of social participation. Results: Participants with higher ACEs scores (≥4) were associated with an increased probability of forward transition (robust to pre-frail, HR = 1.37, 95%CI: 1.21–1.54; prefrail to frail, HR = 1.39, 95%CI: 1.18–1.63) and decreased probability of backward transition (pre-frail to robust, HR = 0.64, 95%CI: 0.55–0.76). Additionally, participants with moderate and high level social participation were associated with an increased probability of backward transition (pre-frail to robust, HR = 1.11, 95%CI: 1.01–1.23; frail to pre-frail, HR = 1.17, 95%CI: 1.02–1.33, respectively). Social participation moderated the association between ACEs exposure and frailty (P for interaction

ABSTRACTBackground: This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML).Methods: Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications.Results: The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods.Conclusion: This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.

Precision weed management (PWM), driven by machine vision and deep learning (DL) advancements, not only enhances agricultural product quality and optimizes crop yield but also provides a sustainable alternative to herbicide use. However, existing DL-based algorithms on weed detection are mainly developed based on supervised learning approaches, typically demanding large-scale datasets with manual-labeled annotations, which can be time-consuming and labor-intensive. As such, label-efficient learning methods, especially semi-supervised learning, have gained increased attention in the broader domain of computer vision and have demonstrated promising performance. These methods aim to utilize a small number of labeled data samples along with a great number of unlabeled samples to develop high-performing models comparable to the supervised learning counterpart trained on a large amount of labeled data samples. In this study, we assess the effectiveness of a semi-supervised learning framework for multi-class weed detection, employing two well-known object detection frameworks, namely FCOS (Fully Convolutional One-Stage Object Detection) and Faster-RCNN (Faster Region-based Convolutional Networks). Specifically, we evaluate a generalized student-teacher framework with an improved pseudo-label generation module to produce reliable pseudo-labels for the unlabeled data. To enhance generalization, an ensemble student network is employed to facilitate the training process. Experimental results show that the proposed approach is able to achieve approximately 76% and 96% detection accuracy as the supervised methods with only 10% of labeled data in CottonWeedDet3 and CottonWeedDet12, respectively. We offer access to the source code (https://github.com/JiajiaLi04/SemiWeeds), contributing a valuable resource for ongoing semi-supervised learning research in weed detection and beyond.

The advent of online education has become indispensable for nursing students seeking to acquire knowledge. However, the efficacy of online education often falls short of initial expectations. Deep learning (DL) can assist learners tackle complex problems and make innovative decisions. Despite its potential, there has been limited exploration into the underlying mechanisms of DL among nursing students, both domestically and globally. This study examined the potential moderating effect of psychological capital (PC) on the association between academic self-concept (AS-c) and DL among nursing students from China enrolled in online courses. Conducted from October 2022 to January 2023, the survey involved 635 nursing students from four public universities in eastern China, utilizing convenience sampling. Data was collected using the AS-c scale, psychological capital scale, and DL scale in online courses. Correlation analyses, univariate analyses, multiple linear regression analyses, and the PROCESS macro were employed for a comprehensive examination. The results revealed a strong positive relationship between nursing students' DL and both their AS-c (r = 0.766, P

BackgroundQingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases.MethodsSix databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace.ResultsA total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of “Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences” and “Shanghai University of Chinese Medicine Cross Academy of Science” have been formed, and two core teams with “Wang Yanping” and “Zhang Weidong” have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research.ConclusionQFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer‐associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF‐derived extracellular vesicle (EV)‐packaged long non‐coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV‐packaged lncRNA RP11‐161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA‐A expression, a key component of antigen presentation. Mechanistically, RP11‐161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4‐NOT complex, enhancing the degradation of HLA‐A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti‐tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA‐based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF‐derived EV‐packaged lncRNA RP11‐161H23.5/CNOT4/HLA‐A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.

Objective To evaluate the safety and efficacy of skin care product containing artemisia naphtha in individuals with sensitive skin. Methods A single-center and self-controlled (before and after application) clinical trial was conducted in 31 subjects with sensitive skin. Test product was applied to the face of the subjects twice daily for 4 weeks. Measurement of physiological function, VISIA-CR photography and lactic acid test were carried out on the skin before and on the days 7,14,28 of the trial. 16S rRNA gene sequencing technology was used to analyze the microecological diversity of the skin surface meanwhile physician and subject' self-assessments were performed. Results Physician assessment scores for erythema were decreased at all three follow-up visits (P

Abstract Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.

To understand the physiological responses of seedlings to mechanical wounding, we analyzed photosynthesis, chlorophyll fluorescence, and endogenous hormones in tomato (Solanum lycopersicum L.) subjected to varying levels of mechanical pressure. The results showed that, at 4 h after wounding, excess excitation energy was dissipated as thermal energy through the reduction in the photosystem II (PSII) opening degree and the increase in non-photochemical quenching. Photodamage was avoided, and stomatal closure was the most prominent factor in photosynthesis inhibition. However, 12 h after wounding, the photoprotective mechanism was insufficient to mitigate the excess excitation energy caused by the wound, leading to photochemical damage to physiological processes. Meanwhile, the non-stomatal factor became the most prominent limiting factor for photosynthesis at 80 N pressure. At 12 and 36 h after wounding, the concentrations of abscisic acid (ABA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), zeatin riboside (ZR), and gibberellic acid (GA3) in the stems showed a trend towards being increased, which promoted wound healing. However, after mechanical wounding, the ratio of stress- to growth-promoting hormones first increased and then decreased. This pattern can enhance stress resistance and promote cell division, respectively. Comprehensive analysis showed that the fluorescence parameter, photochemical quenching coefficient (Qp_Lss), was the most suitable indicator for evaluating mechanical wounding conditions.

When recording the vegetation distribution with a camera, shadows can form due to factors like camera angle and direct sunlight. These shadows result in the loss of pixel information and texture details, significantly reducing the accuracy of fractional vegetation coverage (FVC) extraction. To address this issue, this study proposes an efficient double-exposure algorithm. The method reconstructs the pixel information in shadow areas by fusing normal-exposure and overexposed images. This approach overcomes the limitations of the camera’s dynamic range in capturing pixel information in shadowed regions. The study evaluates images with five levels of overexposure combined with five vegetation extraction indices. The aim is to determine the best-performing double-exposure combination under shadow conditions and the most suitable vegetation index. Experimental results reveal that the R² value between the best vegetation index and the FVC calculated from the fused double-exposure images and the ground truth FVC increases from 0.750 to 0.969. The root mean square error (RMSE) reduces from 0.146 to 0.046, and the intersection over union (IOU) increases from 0.856 to 0.943. These results demonstrate the excellent vegetation extraction capability of the double-exposure algorithm under shadow conditions, offering a straightforward and effective solution to low accuracy of FVC in shadowed areas.

High failure rate is a primary characteristic of current farmer entrepreneurial activities in China. We examined the impact of entrepreneurial failure on the health of Chinese farmers based on the data from the China Labor-force Dynamics Survey (CLDS). We found that entrepreneurial failure significantly depresses the health of Chinese farmers. Specifically, the farmers with entrepreneurial failure experience are more likely to have low self-reported levels of psychological and physical health, and the probability of experiencing severe injury and illness is elevated by 4.6 %. Mechanism analysis shows that entrepreneurial failure depresses the health of Chinese farmers through weakening informal social support and increasing the probability of overwork. Furthermore, these effects are more significant in the older generation of farmers who were born before 1980 and the farmers striving to make a living.

Laser interstitial thermal therapy (LITT), which ablates diseased brain tissues via hyperthermia, has offered novel treatment approach for epilepsy; however, the current LITT protocols still lack ablation selectivity and disease‐modifying efficacy. A second near‐infrared (NIR‐II) activatable nitric oxide (NO) releasing nanoactuator is reported here for photothermal combinational modulation of epileptogenic focus. The nanoactuator is prepared by conjugating NO donor S‐nitrosoglutathione (GSNO) onto polydopamine‐coated gold (Au) nanoparticles (NPs), which shows excellent photothermal conversion capability and controlled NO‐releasing property upon illumination in the NIR‐II window. Both in vitro and in vivo study demonstrate that the nanoactuator could exert stronger cell killing effects as compared to its counterpart. Furthermore, the NIR‐II‐activated NO release could inhibit P‐gp expression by regulating NF‐κb pathway, resulting in reprogramming of epileptogenic microenvironment. This study thus offers a novel regulating strategy for the treatment of drug‐resistant epilepsy.

BackgroundCell transplants as a treatment for Parkinson’s disease have been studied for decades, and stem cells may be the most promising cell sources for this treatment. We aimed to investigate whether stem cell transplantation contributes to the cure for Parkinson’s disease and the factors that may influence the efficacy for this therapy.MethodsPubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and ChinaInfo were thoroughly searched to find controlled trials or randomized controlled trials performing stem cell transplantation in patients with Parkinson’s disease. The pooled effects were analyzed to evaluate the weighted mean difference (WMD) with 95% confidence intervals.ResultsNine articles were identified including 129 individuals. Stem cell transplantation was an effective treatment for Parkinson’s disease (WMD = −14.86; 95% CI: −16.62 to −13.10; p

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

Maker Education (ME) focuses on fostering students’ Maker Mindsets (MM). However, prevailing ME practices often lack a structured approach, that impedes the effective development of students’ MM. To address this challenge, a Design Thinking-making pedagogy (DTMP) is used to design ME lessons through a three-month Lesson Study (LS) cycle. Employing a qualitative multiple case study methodology, we studied the development and transformation of MM in three elementary school students. Diverse data were collected, including student artifacts, video recordings of teacher discussions, and audio recordings of the interviews. The findings revealed common cognitive, self-efficacy, and collaboration improvements among the three students. Unique changes in individual cognitive skills, motivational patterns, and obstacles to collaboration were also observed. Furthermore, key factors influencing MM development were identified across individual, social, and pedagogical dimensions. Individual factors included prior knowledge, maker skills, and motivation, whereas social factors included teachers’ attitudes, recognition, feedback, and peer collaboration. Pedagogical practices, such as project difficulty, structure, and authenticity, play a crucial role in MM development. This study not only contributes valuable insights into MM development, but also underscores the pivotal role of tailored, personal real-life experiences in ME pedagogy. Furthermore, our study suggests that teachers can enhance ME pedagogy by intentionally designing it to facilitate MM in students, using the LS approach.

Background The aim of this retrospective research was to develop an immune-related genes significantly associated with m5C methylation methylation (m5C-IRGs)-related signature associated with lung adenocarainoma (LUAD). Methods We introduced transcriptome data to screen out m5C-IRGs in The Cancer Genome Atlas (TCGA)-LUAD dataset. Subsequently, the m5C-IRGs associated with survival were certificated by Kaplan Meier (K-M) analysis. The univariate Cox, least absolute shrinkage and selection operator (LASSO) regression, and xgboost.surv tool were adopted to build a LUAD prognostic signature. We further conducted gene functional enrichment, immune microenvironment and immunotherapy analysis between 2 risk subgroups. Finally, we verified m5C-IRGs-related prognostic gene expression in transcription level. Results A total of 76 m5C-IRGs were identified in TCGA-LUAD dataset. Furthermore, 27 m5C-IRGs associated with survival were retained. Then, a m5C-IRGs prognostic signature was build based on the 3 prognostic genes (HLA-DMB, PPIA, and GPI). Independent prognostic analysis suggested that stage and RiskScore could be used as independent prognostic factors. We found that 4104 differentially expressed genes (DEGs) between the 2 risk subgroups were mainly concerned in immune receptor pathways. We found certain distinction in LUAD immune microenvironment between the 2 risk subgroups. Then, immunotherapy analysis and chemotherapeutic drug sensitivity results indicated that the m5C-IRGs-related gene signature might be applied as a therapy predictor. Finally, we found significant higher expression of PPIA and GPI in LUAD group compared to the normal group. Conclusions The prognostic signature comprised of HLA-DMB, PPIA, and GPI based on m5C-IRGs was established, which might provide theoretical basis and reference value for the research of LUAD. Public Datasets Analyzed in the Study TCGA-LUAD dataset was collected from the TCGA ( https://portal.gdc.cancer.gov/ ) database, GSE31210 (validation set) was retrieved from GEO ( https://www.ncbi.nlm.nih.gov/geo/ ) database.

BackgroundAngiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored.Case reportA 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months.ConclusionTo the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.

Abstract Background Mucosal healing has become the primary treatment target for patients with Crohn’s disease (CD). We aimed to develop a noninvasive and convenient tool to evaluate the endoscopic activity in patients with ileocolic CD. Methods A retrospective multicenter study including 300 CD patients (training, 210 patients; test, 90 patients) was conducted at two tertiary referral centers. Independent risk factors associated with endoscopic activity were explored, which were then combined into a comprehensive index. The predictive performance was evaluated with the area under receiver operating characteristic curve (ROC). Cohen’s Kappa was adopted to examine the consistency between each indicator and endoscopic activity. Results A total of 210 CD patients were recruited in the training cohort. We found that Crohn’s Disease Activity Index (CDAI), C-reactive protein (CRP) and platelet-to-lymphocyte percentage ratio (PLpR) were independently associated with endoscopic activity. Additionally, the comprehensive index generated from the above three indices achieved good discrimination and performed better than CDAI in AUC (0.849 vs. 0.769, P

This paper studied the characteristics of the carbon emission of an industrial wastewater treatment plant (IWWTP) and a domestic WWTP (DWWTP) located in a high-tech industrial park of Shaanxi Province, China. The results showed that the total carbon emissions of the IWWTP and DWWTP were 10.13 kg/t and 1.84 kg/t in 2020, respectively. Indirect carbon emissions play a dominant role in the total carbon emission of the IWWTP, which accounts for about 97.6% of the total amount. The direct carbon emissions of greenhouse gases (e.g., CH4, N2O) account for about 62% of the total carbon emissions in the DWWTP, followed by the indirect carbon emissions generated by electricity consumption (31.06%) and chemical consumption (6.94%). Additionally, the centralized recycling and re-utilization of the wastewater could achieve 1.06 kg/t and 1.16 kg/t of carbon emission reduction in the IWWTP and DWWTP, respectively, while the carbon emissions of the DWWTP are inversely proportional to the treatment capacity. Therefore, it is of great value to collect and utilize intensively the recycled water to achieve the goal of regional carbon emission reduction and carbon neutralization of WWTPs in industrial parks.

Abstract Background Sugar beet (Beta vulgaris L.) is an economically essential sugar crop worldwide. Its agronomic traits are highly diverse and phenotypically plastic, influencing taproot yield and quality. The National Beet Medium-term Gene Bank in China maintains more than 1700 beet germplasms with diverse countries of origin. However, it lacks detailed genetic background associated with morphological variability and diversity. Results Here, a comprehensive genome-wide association study (GWAS) of 13 agronomic traits was conducted in a panel of 977 sugar beet accessions. Almost all phenotypic traits exhibited wide genetic diversity and high coefficient of variation (CV). A total of 170,750 high-quality single-nucleotide polymorphisms (SNPs) were obtained using the genotyping-by-sequencing (GBS). Neighbour-joining phylogenetic analysis, principal component analysis, population structure and kinship showed no obvious relationships among these genotypes based on subgroups or regional sources. GWAS was carried out using a mixed linear model, and 159 significant associations were detected for these traits. Within the 25 kb linkage disequilibrium decay of the associated markers, NRT1/PTR FAMILY 6.3 (BVRB_5g097760); nudix hydrolase 15 (BVRB_8g182070) and TRANSPORT INHIBITOR RESPONSE 1 (BVRB_8g181550); transcription factor MYB77 (BVRB_2g023500); and ethylene-responsive transcription factor ERF014 (BVRB_1g000090) were predicted to be strongly associated with the taproot traits of root groove depth (RGD); root shape (RS); crown size (CS); and flesh colour (FC), respectively. For the aboveground traits, UDP-glycosyltransferase 79B6 (BVRB_9g223780) and NAC domain-containing protein 7 (BVRB_5g097990); F-box protein At1g10780 (BVRB_6g140760); phosphate transporter PHO1 (BVRB_3g048660); F-box protein CPR1 (BVRB_8g181140); and transcription factor MYB77 (BVRB_2g023500) and alcohol acyltransferase 9 (BVRB_2g023460) might be associated with the hypocotyl colour (HC); plant type (PT); petiole length (PL); cotyledon size (C); and fascicled leaf type (FLT) of sugar beet, respectively. AP-2 complex subunit mu (BVRB_5g106130), trihelix transcription factor ASIL2 (BVRB_2g041790) and late embryogenesis abundant protein 18 (BVRB_5g106150) might be involved in pollen quantity (PQ) variation. The candidate genes extensively participated in hormone response, nitrogen and phosphorus transportation, secondary metabolism, fertilization and embryo maturation. Conclusions The genetic basis of agronomical traits is complicated in heterozygous diploid sugar beet. The putative valuable genes found in this study will help further elucidate the molecular mechanism of each phenotypic trait for beet breeding.

The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing the therapeutic results. Targeting the tumor microenvironment is a promising cancer treatment method in recent years. The importance of tumor immune microenvironment regulation by ultrasound combined with microbubbles is now widely recognized. Ultrasound and microbubbles work together to induce antigen release of tumor cell through mechanical or thermal effects, promoting antigen presentation and T cells’ recognition and killing of tumor cells, and improve tumor immunosuppression microenvironment, which will be a breakthrough in improving traditional treatment problems such as immune checkpoint blocking (ICB) and himeric antigen receptor (CAR)-T cell therapy. In order to improve the therapeutic effect and immune regulation of TME targeted tumor therapy, it is necessary to develop and optimize the application system of microbubble ultrasound for organs or diseases. Therefore, the combination of ultrasound and microbubbles in the field of TME will continue to focus on developing more effective strategies to regulate the immunosuppression mechanisms, so as to activate anti-tumor immunity and/or improve the efficacy of immune-targeted drugs, At present, the potential value of ultrasound combined with microbubbles in TME targeted therapy tumor microenvironment targeted therapy has great potential, which has been confirmed in the experimental research and application of breast cancer, colon cancer, pancreatic cancer and prostate cancer, which provides a new alternative idea for clinical tumor treatment. This article reviews the research progress of ultrasound combined with microbubbles in the treatment of tumors and their application in the tumor microenvironment.

The Qinghai-Tibet Plateau (QTP) has experienced an overall increase in humidity over recent decades, but the changes in aridity and humidity within the transitional climate zone, as well as the underlying factors driving these changes, remain unclear. We present a framework to quantify the spatiotemporal variations transitional zone indicated by 400 mm isohyets and its driving factors on the QTP. The results show that the 400 mm isohyets has moved an average of 87.85 km to the north-west direction, moving an average 0.04 km per year, and a maximum distance traveled of 261 km (northernmost orientation) during the past four decades. Over time, the variation in isohyets exhibited distinct piecewise characteristics and obvious spatial differences. The central section (95°E–101°E) remained relatively stable, whereas the eastern section (101°E–104°E) and western section (91°E–95°E) experienced violent fluctuations. The east–west boundary of the spatiotemporal movement of the 400 mm isohyets was utilized to delineate the eastern humid zone, transitional zone, and western arid zone. The transition zone interannual precipitation has experiences more significant interdecadal oscillations between dry and wet climates, while the western region has experienced the opposite. The East Asian summer monsoon (EASM) exhibited a positive correlation with precipitation, increased precipitation is the main factor driving the westward and northward movement of the 400 mm isohyets. The vegetation response to precipitation exhibited greater variability in the transitional zone. This study provides a novel reference for quantitatively comprehending the aridity and humidity of climatic conditions, as well as the driving mechanisms behind regional climate change in the QTP.

Although the arsenic contamination and antibiotic resistance genes (ARGs) during composting have been studied separately, there is limited information on their interactions, particularly, the relationship between arsenic biotransformation genes (ABGs) and ARGs. Therefore, the present study used different forms of arsenic stress (organic and inorganic arsenic at 10 and 50 mg/kg) in pig manure and straw co-composting, to evaluate the effects of arsenic stress on microbial community structures, metabolic function, ABGs, and ARGs. The results showed that arsenic stress had different effects on different parameters and promoted the microbial formation of humic acid and the biodegradation of fulvic acid. Inorganic arsenic showed more rapid effects on microbial community structure, visible within about 20 days, while the effects of organic arsenic were later (about 45 days) due to the necessity of transformation. Moreover, the addition of organic roxarsone and inorganic arsenic resulted in higher expression of ABGs and ARGs, respectively. Arsenic addition also caused increased expression of genes associated with replication and repair. A significant relationship was observed between ABG and ARG expression, for instance, genes involved in arsenic reduction and oxidation were influenced by genes involved in aminoglycoside and chloramphenicol resistance genes (p

Background: We aimed to evaluate the impacts of short-term daily temperature variability (DTV) on blood pressure (BP) among participants with normotension, prehypertension, and hypertension, respectively, and explore the effects in different climate zones and seasons. Methods: A representative population sample (n = 397,173) covering the subtropical, temperate continental, and temperate monsoon zones was obtained from the China Hypertension Survey. DTV was calculated as the standard deviation of daily minimum and maximum temperatures during the exposure days. The linear mixed effect regression model was used to estimate the associations between DTV exposure and BP among normotension, prehypertension, and hypertension, respectively, and further stratified analysis was performed by climate zones and seasons. Results: After adjustment for confounders, per interquartile range (IQR) increase in DTV (2.28 °C) at 0–6 days of exposure was associated with an increase of 0.41 mmHg (95 % confidence interval [CI]: 0.07, 0.75) in systolic BP (SBP) and 0.41 mmHg (95 % CI: 0.09, 0.72) in pulse pressure (PP) among hypertensive participants in the subtropical zone. Similarly, DTV exposure was associated with an increase of 0.31 mmHg (95 % CI: 0.06, 0.55) in SBP and 0.59 mmHg (95 % CI: 0.24, 0.94) in PP among prehypertensive participants in the temperate continental zone. Additionally, during the warm season, DTV was positively associated with SBP among populations with prehypertension and hypertension, and with PP among all three populations. Conclusion: Short-term DTV exposure was associated with an increase in SBP and PP among hypertensive and prehypertensive participants in the subtropical zone and the temperate continental zone. In addition, positive associations of DTV with SBP and PP were observed among participants with prehypertension and hypertension in the warm season. Comprehensive health education and effective intervention strategies should be implemented to mitigate the effects of temperature variations on BP, particularly among prehypertensive and hypertensive populations.