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Abstract Fusarium head blight (FHB) not only causes severe yield losses but also mycotoxin contamination in wheat, posing a serious threat to food security and public health. The mechanisms of resistance to FHB in wheat are critical for effective prevention and control of the pathogen. In this research, we investigated and analyzed the metabolite changes induced by FHB colonization in the FHB-resistant cultivar Lianmai12 through Fusarium graminearum inoculation and mock inoculation. A total of 1001 metabolites were detected, 109 of which were significantly changed due to FHB infection. The majority of these 109 metabolites belonged to alkaloids, flavonoids, phenolic acids, lipids and organic acids. The most enriched KEGG pathways were plant hormone signal transduction and phenylpropanoid biosynthesis, which may constitute the major defence responses to FHB challenge. The metabolite p-aminobenzoic acid (PABA) significantly suppressed the growth of mycelia and the production of conidia in vitro. Further studies revealed that spraying PABA at early anthesis on wheat spikes reduced the development of FHB disease. These results provide preliminary insights into the metabolic basis of resistance in Lianmai12 and will be beneficial in the development of potential biocontrol agents against FHB. Graphical Abstract

Abstract Objective This study sought to evaluate the value of a CO2 field-flooding device in cardiopulmonary bypass (CPB) surgical procedures for congenital heart disease (CHD) performed via a right-side small incision approach. Methods Between April 2022 and December 2023, 234 children with simple CHD who underwent CPB via a right-side small incision approach were separated into a control group (n = 93) without the use of a CO2 field-flooding device and a treatment group (n = 141) in which this device was added to the traditional surgical manual exhaust. Demographic, perioperative, arterial blood gas (ABG), and laboratory test data were then compared between these groups of patients. Results There was a significant difference in abnormal electrocardiogram (ECG) after aorta de-clamping during CPB, and interventions for abnormal ECG after aorta de-clamping during CPB between the control and treatment groups (17(18.3%) vs.14(9.9%), P = 0.048;12(85.7%) vs.7(50%),P = 0.013). The treatment group exhibited a lower pH (7.34 ± 0.07 vs. 7.36 ± 0.06, P = 0.039) and a higher PaCO2 (43.08 ± 7.36 vs. 38.86 ± 5.65 mmHg, P = 0.042) at the time of 30 min after initiation of CPB. A significant reduction in postoperative CK-MB was observed in treatment group (41.20 ± 17.88 vs. 56.57 ± 22.99 U/L, P = 0.002). Lower 3-day postoperative CRP levels were also observed in the treatment group relative to control (5.77 ± 0.48 vs. 9.45 ± 0.98 mg/L, P

Major facilitator superfamily (MFS) transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism. Peronophythora litchii causes the most destructive disease on lichi, litchi downy blight. PlM90 was reported as a key oosporogenesis regulator. Here, we identified an MFS transporter gene PlMFS1, which is up-regulated during oospore formation at the late infection stage, while down-regulated in the PlM90 mutant. To investigate PlMFS1 function, we generated PlMFS1 knockout mutants using CRISPR/Cas9-mediated genome editing technology. Compared with the wild-type strain SHS3, PlMFS1 deletion impaired mycelium growth, zoospore release, oospore production and pathogenicity. Furthermore, PlMFS1 deletion significantly affected P. litchii utilization of fructose, lactose and maltose, and may be the PlMFS1 mechanism involved in mycelial growth. PlMFS1 gene deletion also led to deceased laccase activity, laccase-encoding gene downregulation and impaired P. litchii pathogenicity. To our knowledge, this is the first report of an MFS transporter involved in sugar utilization, sexual reproduction, asexual reproduction and pathogenesis in oomycetes.

Abstract Background Sleep disturbance is a common concern among stroke survivors, yet the association of sleep duration and sleep disorders with post-stroke depression and all-cause and cardiovascular disease (CVD) mortality remains elusive. We aimed to explore these associations using data from the National Health and Nutrition Examination Survey (NHANES). Methods Adult stroke survivors from NHANES 2005–2018 were included. Sleep information and stroke diagnoses were derived from self-reports on relevant questionnaires. Mortality data were collected by prospectively matching to the National Death Index. Multivariate logistic regression and Cox proportional hazards regression were used to explore these associations and calculate the odds ratio (OR) and hazard ratio (HR), respectively. Results A total of 1101 stroke participants were included. In the fully adjusted model, sleep disorders were associated with increased odds of post-stroke depression (OR 2.689, p = 0.0146). Sleep duration was inversely associated with the odds of post-stroke depression; compared to normal sleep duration, short sleep duration was associated with increased odds of post-stroke depression (OR 2.196, p = 0.0059), whereas long sleep duration was not (p = 0.1435). Sleep disorders were associated with CVD mortality (HR of 1.948, p = 0.026) but not all-cause mortality (p = 0.224) in stroke survivors. Sleep duration was positively associated with all-cause mortality in stroke survivors (HR 1.075, p = 0.042); however, neither short nor long sleep duration was associated with mortality compared to normal sleep duration. Restricted cubic spline modeling suggested that sleep duration was nonlinearly and linearly associated with post-stroke depression and all-cause mortality, respectively. Age influenced the association between sleep disorders and CVD mortality in stroke survivors. Conclusions Sleep disorders and short sleep duration were associated with increased odds of post-stroke depression, whereas sleep disorders were associated with increased CVD mortality in stroke survivors. These findings underscore that achieving normal sleep duration and improving sleep disorders may reduce the odds of post-stroke depression and mortality.

Abstract Background In acquired immunodeficiency syndrome patients, Talaromyces marneffei infections are mostly disseminated and may involve the skin, mucosa, respiratory system, digestive system, lymphatic system, and as some reports indicate, the nervous system. Mp1p, a cell wall-specific polysaccharide in Talaromyces marneffei, is used for laboratory diagnosis of Talaromyces marneffei in blood and urine samples. However, Cerebrospinal fluid Mp1p diagnosis of Talaromyces marneffei central nervous system infection has not been reported. Case presentation We present the case of an acquired immunodeficiency syndrome 35-year-old woman who has had dizziness and headache and was infected with central nervous system Talaromycosis.Magnetic resonance imaging scan which showed intracranial infectious lesions, altered brain atrophic, and periventricular demyelination.The Mp1p antigen was positive by using immunofluorescence in the Cerebrospinal fluid. Talaromyces marneffei was isolated from the Cerebrospinal fluid.After antifungal treatment, her clinical symptoms significantly improved. Conclusions Talaromyces marneffei central nervous system infection is rare. If the patient has symptoms of central nervous system, the Cerebrospinal fluid Mp1p antigen and culture should be performed to make a definitive diagnosis.

Abstract The lysine-specific demethylase 5 (KDM5) family, a key post-translational modification of chromatin, can shape tumor immune microenvironment. Here, we performed an extensive clinical and bioinformatic analysis to explore the association between KDM5 mutation and tumor immunity and its impact on the outcomes in pan-cancer immunotherapy. In 2943 patients across 12 tumor types treated with immune checkpoint inhibitors, KDM5-mutant tumors were associated with favorable overall survival (hazard ratio, 0.72; 95% confidence interval, 0.59–0.87; P = 0.004) and objective response rate (41.7% vs. 26.8%; P = 0.001). Further multi-omics analysis revealed KDM5 mutation was related to boosted tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, KDM5 mutation indicates enhanced tumor immunity and favorable outcomes in pan-cancer immune checkpoint blockade. These results have implication for treatment decision-making and developing immunotherapy for personalized care.

Abstract The network layer plays a crucial role in blockchain systems, enabling essential functions such as message broadcasting and data synchronization. Enhancing data transmission structures and methods at this layer is key to improving scalability and addressing performance limitations. Currently, the uneven distribution of neighboring node lists and the lack of awareness of underlying linkages in coverage networks hinder the efficiency and comprehensiveness of information transmission. To tackle these challenges, this study introduces a dual-layer transmission model, FPSblo-EP, which divides the blockchain P2P network into two layers: the regular node layer and the tagged node layer. In the initial stage, network nodes are treated as points in a point cloud, and farthest point sampling is applied to the P2P network nodes. During this process, geographic distances between nodes serve as input parameters, while node degrees are used as point weights. Tagged nodes can then provide efficient and stable inter-group routing for regular nodes, creating a hierarchical transmission architecture. This model improves both transmission performance and scalability in blockchain overlay networks. Experimental results show that FPSblo-EP reduces message coverage latency by 22%, redundancy by 26%, and the network stretch coefficient by 28%, demonstrating superior load-balancing capabilities and enhanced network reliability.

Abstract Objective Berry syndrome is a group of rare congenital cardiac malformations including aortopulmonary window (APW), aortic origin of the right pulmonary artery (AORPA), interruption of the aortic arch (IAA), patent ductus arteriosus (PDA) (supplying the descending aorta) and intact ventricular septum. This paper will analyze the clinical data of 7 patients with Berry syndrome who underwent surgical treatment in our institution and discuss the one-stage surgical correction of Berry syndrome in combination with the literature. Methods From January 2013 to July 2024, a total of 7 children with Berry syndrome were admitted to the Cardiac Surgery Department of Beijing Children’s Hospital. The median age was 3 months (range, 1–36 months). All patients’ IAA morphology were type A. The APW morphology was type IIA in 2, type IIB in 4, and type III in 1 patient. Three different surgical correction techniques were used to repair the APW and AORPA, including intra-aortic patch in 2, RPA angioplasty with aortic cuff in 2, RPA detachment and reimplant in 3 patients. Results Among the 7 patients, one died in the early postoperative period, (1/7, 14.3%). The remaining 6 surviving patients, mechanical ventilation was lasted for 51 to 166 h postoperatively, with an average of (113.3 ± 50.8) hours; the CCU stay was 6 to 23 days, with an average of (11.8 ± 6.5) days. Two cases (2/7, 28.6%) of patients adopted the strategy of delayed sternal closure. The 6 surviving children were followed up for a period ranging from 3 to 132 months, with a median follow-up duration of 36 months. During the follow-up, 2 patients underwent a second operations (2/6, 33.3%). The remaining 4 patients showed no obvious RPA stenosis, descending aorta (DAO) stenosis, aortic valve stenosis or aortic valve regurgitation (AR) during the follow-up period. In the latest follow-up, the average velocity of the RPA of the 4 patients was 1.68 ± 0.36 m/s, and the average pressure gradient was 11.9 ± 4.8 mmHg; the average velocity of the DAO was 2.1 ± 1.7 m/s, and the average pressure gradient was 17.9 ± 2.6 mmHg. All the AR were less than mild. Conclusion Most children can achieve one-stage surgical correction. For children with APW type IIA, the intra-aortic patch method can be attempted, but its therapeutic effect still requires medium to long-term follow-up. The surgical approach of RPA detachment and reimplant can be applied to all types of patients with Berry syndrome, and the medium to long-term follow-up result is favorable. For the treatment of IAA, it is recommended that end-to-side anastomosis be performed between the DAO and the aortic arch, and the anterior wall be augmented by using bovine pericardial tissue patches. For the residual obstruction at the postoperative anastomosis site, balloon dilation angioplasty can be considered. Compression of the left main bronchus can be supported by intratracheal stents. Perspective Statement In the English literature accessed thus far, there are less than 50 cases associated with the surgical treatment of Berry syndrome. In this work, we analyzed the clinical data of 7 patients from January 2013 to July 2024 with Berry syndrome who underwent surgical treatment in our institution and showed one-stage surgical correction can achieved acceptable outcomes. Graphical Abstract

Abstract Background This study aims to develop habitat radiomic models to predict overall survival (OS) for hepatocellular carcinoma (HCC), based on the characterization of the intratumoral heterogeneity reflected in 18F-FDG PET/CT images. Methods A total of 137 HCC patients from two institutions were retrospectively included. First, intratumoral habitats were achieved by a two-step unsupervised clustering process based on k-means clustering. Second, a total of 4032 radiomic features were extracted based on each habitat, including 2016 PET-based and 2016 CT-based radiomic features. Then, after feature selection, the stacking ensemble learning approach which combined six machine learning classifiers as the first-level learners with Cox proportional hazards regression as the second-level learner, was employed to build multiple radiomic models. Finally, the optimal model was selected based on the calculation of the C-index, and a combined model integrating with a clinical model was also constructed to identify the potentially complementary effect. Results Three spatially distinct habitats were identified in the two cohorts. Among a total of 30 stacking ensemble learning models established based on different combinations of 5 types of segmented volumes of interest (VOIs) with 6 types of classifiers, the MLP-Cox-habitat-2 model was selected as the optimal radiomic model with a C-index of 0.702 in the external validation cohort. Furthermore, the combined model integrating the optimal radiomic model with the clinical model achieved an improved C-index of 0.747. Consistently, the combined model outperformed the other models for OS prediction, with a time-dependent AUC of 0.835, 0.828, and 0.800 in the 1-year, 2-year, and 3-year OS, respectively. Conclusion 18F-FDG PET/CT-based habitat radiomics outperformed traditional radiomics in OS prediction for HCC, with a further improved predictive power by integrating with the clinical model. The optimal combined habitat model was potentially promising in guiding individualized treatment for HCC. Trial registration This study was a retrospective study, so it was free from registration.

Abstract The widespread bacterial genus Sulfurimonas is metabolically versatile and occupies a key ecological niche in different habitats, but its interaction with bacteriophages remains unexplored. Here we systematically investigated the genetic diversity, taxonomy and interaction patterns of Sulfurimonas-associated phages based on sequenced microbial genomes and metagenomes. High-confidence phage contigs related to Sulfurimonas were retrieved from various ecosystems, clustered into 61 viral operational taxonomic units across three viral realms, including Duplodnaviria, Monodnaviria and Varidnaviria. Head-tail phages of Caudoviricetes were assigned to 19 genus-level viral clusters, the majority of which were distantly related to known viruses. Notably, diverse double jelly-roll viruses and inoviruses were also linked to Sulfurimonas, representing two commonly overlooked phage groups. Historical and current phage infections were revealed, implying viral impact on the evolution of host adaptive immunity. Additionally, phages carrying auxiliary metabolic genes might benefit hosts by compensating or augmenting sulfur metabolism. This study highlights the diversity and novelty of Sulfurimonas-associated phages with divergent tailless lineages, providing basis for further investigation of phage-host interactions within this genus.

This study aimed to investigate the application of the cup‐on‐cup technique in revision total hip arthroplasty (THA) and report clinical and radiographic outcomes from a series of case follow‐ups. Retrospective analysis of 10 patients who underwent acetabular prosthesis revision with cup‐on‐cup technique. According to the Paprosky classification of acetabular bone defects, there were 2 cases of type II C, 3 cases of type III A, and 5 cases of type III B. The average follow‐up was 54.8 ± 5.1 months, and the Harris score of the hip joint increased from 37.0 ± 9.9 preoperatively to 80.5 ± 3.1 postoperatively at the final follow‐up (p

Abstract Significant strides have been made in understanding El Niño-Southern Oscillation (ENSO) dynamics, yet its long-lead prediction remains challenging, especially for the El Niño events after 2000. Sea surface salinity (SSS) is known to affect ENSO development and intensity by influencing ocean stratification and heat redistribution and therefore, when combined with sea surface temperature (SST) data, can potentially enhance ENSO forecast skill. In this study, we develop a deep learning (DL) model that incorporates a multiscale-pyramid structure and spatiotemporal feature extraction blocks, and the model successfully extends effective ENSO forecast lead time to 24 months for 2000–2021 with reduced effect of the spring predictability barrier (SPB). Interpretable methods are then applied to reveal the time-dependent roles of SST and SSS in ENSO forecast. More specifically, SST is critical for short-medium lead forecasts (6 months). Furthermore, we track global SST and SSS spatiotemporal shifts related to subsequent ENSO development, highlighting the importance of ocean inter-basin and tropics-extratropics interactions. With increasing availability of satellite SSS observations, our findings unveil unprecedented potential for advancing ENSO long-lead forecast skills.

Abstract Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2−4 orders of magnitude to 22 μs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector’s ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.

Abstract Background Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. Method This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. Results One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. Conclusion ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by the overproliferation of synovial fibroblast‐like synoviocytes (FLSs) in the lining, leading to chronic inflammation and progressive joint damage. RA pathogenesis involves lymphocyte infiltration, increased synovial cell proliferation, and impaired cell death. This study investigated the effects of rapamycin on RA‐FLSs and explored the underlying molecular mechanisms. Methods The optimal drug concentration and time for rapamycin administration were determined using a cell counting kit‐8 assay. The concentration of rapamycin varied from 1 to 25 nmol/L. The mRNA expression levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), B cell lymphoma 2 (Bcl‐2), and Bcl‐2‐associated X protein (Bax) were quantified by real‐time polymerase chain reaction. Protein expression (p‐AKT, AKT, p‐mTOR, mTOR, pS6 kinase [S6K], S6K, p‐4E‐binding protein 1 [4EBP1], 4EBP1, Bcl‐2, Bax, caspase 3, caspase 9, cyclin‐dependent kinase 2 [CDK2], and CD1) were detected by Western blotting analysis. Results Rapamycin suppresses RA‐FLS proliferation and induces apoptosis in a dose‐dependent manner. Rapamycin significantly elevated the protein expression of Bax (p

ObjectiveCirculating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of immune homeostasis. Perhaps, there is a unique immune cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of autoimmune diseases. This study focused on the uniqueness of D2T RA lymphocyte subsets and the feasibility of low-dose IL-2 therapy.MethodsParticipants included 1,042 RA patients who were divided into three groups according to the presence or absence of treatment and their response to treatment in the last 6 months—new group, treated group, and D2T group—and 339 healthy controls (HCs). A total of 381 patients—107, 151, and 123 in each of the three experimental groups—received low-dose IL-2 treatment [0.5 million international units (MIU) per day, subcutaneous injection from day 1 to day 5]. The absolute numbers of peripheral blood lymphocyte subsets were detected by flow cytometry (FCM) and serum cytokine levels were detected by flow cytometry bead array (CBA).ResultsThe absolute number of T, CD4+ T, and Treg cells in the D2T RA group was lower than that in the HC, new, and treated RA groups. Compared with the HC and new RA group, the ratio of Th17/Treg cells in the D2T RA group increased. The new, treated, and D2T RA groups had higher cytokine levels than the HC. The number of Treg cells in RA patients was negatively correlated with the disease activity index. Treg cells in the new, treated, and D2T RA groups could be increased by low-dose IL-2 therapy without any side effects.ConclusionsThe number of lymphocytes and subsets in D2T RA patients was reduced, especially Treg cells, resulting in a shift in the balance of effector T cells/Treg cells toward effector T cells, which is ameliorated by low-dose IL-2 without obvious side effects.

Background and objective: Though several clinicopathological features are identified as prognostic indicators, potentially prognostic radiomic models are expected to preoperatively and noninvasively predict survival for HCC. Traditional radiomic models are lacking in a consideration for intratumoral regional heterogeneity. The study aimed to establish and validate the predictive power of multiple habitat radiomic models in predicting prognosis of hepatocellular carcinoma (HCC). Methods: A total of 232 HCC patients were retrospectively included, including a training/validation cohort and two external testing cohorts from 4 centers. For habitat radiomics, intratumoral habitat partitioning based on CT images was first performed by using Otsu thresholding method. Second, a total of 350 habitat radiomic models were constructed to select the optimal model. Then, both ROC curve analyses and Kaplan-Meier survival curve analyses were applied to assess the predictive performances. Ultimately, an immune status profiling was conducted based on bioinformatic analyses and multiplex immunohistochemistry (mIHC) assays to reveal the potential mechanisms. Results: A total of 4 habitats were segmented, and the corresponding habitat radiomic models were constructed based on each habitat and an integration of all the four habitats. Generally, habitat radiomic models outperformed traditional radiomic models in stratifying prognosis for HCC. The habitat radiomic model based on the segmented habitat 4 involving decision tree (DT) screening and random forest (RF) classifier was identified as the optimal model with an AUCmean of 0.806. Distinct resting natural killer (NK) cell infiltrations significantly contributed to the prognosis stratification of HCC by the optimal habitat radiomic model. Conclusions: The habitat radiomic model based on CT images was potentially predictive of overall survival for HCC, with a superiority over the traditional radiomic model. The prognostic power of the habitat radiomic model was partly attributed to the distinct immune status captured in the CT images.

Soil salinization, which is significantly influenced by groundwater storage dynamics, leads to reduced land productivity, loss of arable land, and degradation of vegetation, thereby posing a substantial threat to global food security and ecosystem functions. The western Songnen Plain (WSP) is one of the world’s three largest concentrations of soda saline-alkaline regions. However, the availability of observed data on groundwater storage dynamics in the WSP remains limited, potentially impeding the evaluation of their impacts on soil salinization processes. This study investigated the impact of groundwater storage variability on soil salinization in the WSP, utilizing multi-source satellite data, the Global Land Data Assimilation System hydrological model data, and ground observation data. Our results demonstrated that groundwater storage anomalies (GWSAs) exhibited cyclical fluctuations from 2002 to 2014, followed by a substantial decline of 13.215 cm equivalent water height from 2015 to 2021. GWSAs exhibited a significant positive relationship with the area of medium-salinized soils that comprised over 56 % of the total salinized soil area. Both the area and degree of soil salinization overall decreased in the WSP due to the decline in groundwater storage and the implementation of soil improvement policies. Our results suggest that targeting soil treatment projects on salinized soils that are less affected by groundwater conditions could potentially mitigate soil salinization in the WSP. This study assessed the potential impact of groundwater storage variability on soil salinization, enhancing mechanisms underlying salinization processes and offering valuable data to inform land and water resources management in salinization-prone regions.

PurposeTo evaluate the corneal biomechanical properties of phacoemulsification in the treatment of cataract patients.MethodsPertinent studies were searched in PubMed, EMBASE, Web of Science and clinicaltrials.gov., as of November 05, 2024. The reference lists of related published reviews were included as well. This meta-analysis was performed with Stata Software and Review Manager, we used mean difference (MD) to evaluate the statistical consequence, using I2 statistic to assess the heterogeneity. Subgroup analysis were performed under the occurrences of high heterogeneity. We used eleven items to describe the characteristics of included studies, publication bias was performed with Egger's test. The quality assessment were evaluated with 3 items by Newcastle-Ottawa Scale (NOS) items.ResultsThirteen eligible studies were identified for data synthesis and assessment. According to the result of meta-analysis, the central corneal thickness(CCT) (MD = 10.50, 95% CI: [5.01, 15.98]; PConclusionIncluded data analysis indicated that the values of CCT, CH, CRF and IOPg showed statistical change in cataract patients after phacoemulsification surgeries compared with control groups. There is a correlation between corneal biomechanics and phacoemulsification surgeries.

ABSTRACT Objective Provide an evidence‐based basis for the selection of cardiovascular benefit drugs in Type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD). Methods Conduct a comprehensive search of all relevant literature from PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials.gov from their establishment until December 13, 2023, and select randomized controlled trials (RCTs) that meet the pre‐established inclusion and exclusion criteria. Use the Cochrane bias risk assessment tool to evaluate the quality of the included literature. Use R 4.3.2 software to conduct network meta‐analysis for drug category comparison. Results A total of 24 large‐scale randomized controlled trials (RCTs) were included, including 19 intervention measures, and 172 803 patients participated in the study. The results of the network meta‐analysis show that: GLP1RA (OR 0.89, 95% CI 0.81–0.97) and SGLT2i (OR 0.91, 95% CI 0.83–0.99) can reduce the occurrence of major adverse cardiovascular events (MACE), GLP1RA (OR 0.88, 95% CI 0.79–0.97) and SGLT2i (OR 0.89, 95% CI 0.81–0.99) reduced the risk of cardiovascular death. SGLT2i (OR 0.68, 95% CI 0.62–0.75) reduced the occurrence of hospitalization for heart failure, GLP1RA (OR 0.88, 95% CI 0.81–0.97) and SGLT2i (OR 0.89, 95% CI 0.80–0.97) reduced the occurrence of all‐cause death. Conclusion In the comparison of new hypoglycemic drug classes, GLP1RA and SGLT2i reduced MACE, cardiovascular mortality and all‐cause mortality in T2DM patients with CVD, with no significant difference in efficacy, and DPP4i was noninferior to placebo. Only GLP1RA reduced the risk of nonfatal stroke, and only SGLT2i reduced the risk of HHF.

ABSTRACT The temperature of metal‐based facilities rises significantly under high outdoor solar irradiation, leading to serious safety accidents. The application of active cooling technology poses challenges due to its high energy consumption, especially in complex outdoor environments. Passive cooling devices with high solar reflection and thermal emission can continuously cool objects under sunlight. However, the white or silvery passive cooling devices do not meet the need for aesthetics and specific demands. Here, we present a hierarchical metapaint for outdoor facilities that simultaneously achieve vibrant color and passive cooling ability. The top layer selectively absorbs visible wavelengths to display desired colors, while the underlayer boosts the reflection of near‐to‐short wavelength infrared (NSWIR) light to prevent solar heating. The metapaint‐coated metal is resistant to high and low temperatures, acidic and alkaline environments, and simulated seawater. It also has satisfactory anti‐fouling properties. When compared to metal coated without commercial paint, the hierarchical passive cooling paint (metapaint) coated metal can cool up to 9.7°C and 17.1°C. The metapaint has excellent passive cooling performance, attributed to its broad‐spectrum selective regulation function. Our work offers a simple, inexpensive, and scalable approach to reduce cooling energy usage and promote a low‐carbon lifestyle.

Copper is an essential micronutrient involved in various physiological processes in various cell types. Consequently, dysregulation of copper homeostasis—either excessive or deficient—can lead to pathological changes, such as heart failure (HF). Recently, a new type of copper-dependent cell death known as cuproptosis has drawn increasing attention to the impact of copper dyshomeostasis on HF. Notably, copper dyshomeostasis was associated with the occurrence of HF. Hence, this review aimed to investigate the biological processes involved in copper uptake, transport, excretion, and storage at both the cellular and systemic levels in terms of cuproptosis and HF, along with the underlying mechanisms of action. Additionally, the role of cuproptosis and its related mitochondrial dysfunction in HF pathogenesis was analyzed. Finally, we reviewed the therapeutic potential of current drugs that target copper metabolism for treating HF. Overall, the conclusions of this review revealed the therapeutic potential of copper-based therapies that target cuproptosis for the development of strategies for the treatment of HF.

Abstract Monsoonal precipitation is dominated by intraseasonal variabilities, whose skillful prediction lead time is currently less than 5 days and remains a grand challenge. Here we show that an intrinsic variability in the Indian Ocean, the Central Indian Ocean (CIO) mode, when combined with a machine learning (ML) algorithm, can produce skillful predictions of intraseasonal precipitation over the monsoon region with a lead time of over 15 days, which is close to the theoretical predictability limit. This remarkable skill improvement stems from the fact that the CIO mode is dynamically related to the intraseasonal monsoon rainfall, while the data‐driven ML algorithm suppresses unwanted high‐frequency noise. Using the CIO mode and the ML algorithm, the forecast system hybridizes physical fundamentals and versatility of data‐driven algorithms. The identification of CIO mode and the verification of its significant contribution to intraseasonal predictions advance our understanding of the coupled monsoon system and also underscores the great potential of ML techniques in weather forecasts and climate predictions.

BackgroundOxidative stress has an important role in type 2 diabetes (T2D). Oxidative balance score (OBS) is an emerging assessment of dietary and lifestyle oxidative balance. We aimed to explore the association of OBS with cardiovascular disease (CVD) and all-cause and CVD mortality in the T2D population through NHANES 1999-2018.MethodsOBS integrated 16 dietary components and 4 lifestyle components. T2D was diagnosed according to the American Diabetes Association criteria. Multivariate logistic regression and multivariate Cox proportional hazards regression analyses were used to explore the association of OBS with CVD and mortality in T2D, respectively.Results3801 adult T2D participants were included. In fully adjusted models, OBS, dietary OBS, and lifestyle OBS were all negatively associated with the prevalence of CVD (odds ratios of 0.98, 0.98, and 0.85, respectively). Higher OBS and lifestyle OBS (p for trend 0.016 and

Background PDZ And LIM domain protein 1 (PDLIM1), a protein-coding gene, has been widely reported to exhibit differential expression patterns across various human cancers, including hematological malignancies. This study aimed to investigate PDLIM1 expression pattern and its functional role in diffuse large B-cell lymphoma (DLBCL) both in vitro and in vivo.Methods PDLIM1 expression patterns were reanalyzed using data from the Gene Expression Omnibus, and the results were subsequently validated in patient tissue samples and a panel of four DLBCL cell lines. MicroRNA-3940-5p (miR-3940-5p) was identified as an upstream regulator of PDLIM1. The interaction between PDLIM1 and miR-3940-5p and its effects on DLBCL cellular activities and cancer development were further explored using a DLBCL mouse model.Results Elevated PDLIM1 expression was observed in DLBCL cells and tissues. Reduced cell proliferation and increased DLBCL cell apoptosis were observed following the knockdown of this gene. Furthermore, short hairpin RNA (shRNA)-mediated PDLIM1 knockdown diminished tumorigenesis of DLBCL cells in nude mice. miR-3940-5p was identified as an upstream regulator of PDLIM1. PDLIM1 expression and function were negatively modulated by the upregulation of miR-3940-5p, consequently affecting the malignant phenotype of DLBCL cells.Conclusion These findings suggest that the miR-3940-5p/PDLIM1 axis may play a crucial role in DLBCL pathogenesis and could potentially be exploited for therapeutic interventions.

ABSTRACTMultispectral images make it possible to retrieve water quality parameters over a wide range and long time series by remote sensing. The robustness of traditional supervised machine learning models, which have been widely used, is affected in various regions, and these models are developed by in-situ measurements and limited satellite images. This study combined a spectral transfer learning strategy with a semi-supervised regression model to conduct data augmentation and developed a robust model for two inland lakes in Jilin Province, Northeast China, based on Sentinel-2 Multispectral Instruments images. Specifically, this study integrated an automated module for Balance Distribution Adaptation and a spectral features transfer method, and then applied it to Co-training Regressors for Chlorophyll-a retrievals to achieve the highest accuracy, which solved the selection of parameters and models. The Automated model was developed and achieved the best performance (R2 is 0.91, the root mean square error is 2.62 μg L−1 and the mean absolute percentage error is 22.88%) compared with other models, and showed robustness in various lakes and months. Our results offer a reliable approach to provide an accurate Chlorophyll-a estimation of spatial–temporal variations.

Microbial fermentation is an effective method to enhance the bioavailability of herbs. This study utilized Lactiplantibacillus plantarum LZU-J-Q21 to ferment Cistanche deserticola and evaluated its metabolic properties and biological activity. Results showed that the contents of total acid and flavone, and the clearance rates of DPPH, ABTS and OH− in fermented Cistanche deserticola (FCD) were increased by 142.74 %, 56.45 %, 58.1 %, 62.3 %，51.2 %, compared with non-fermented Cistanche deserticola (NFCD). The metabolic profile of FCD had remarkable changes, especially elevated glucose and adenosine (97.31 % and 59.18 %). Further, FCD increased the weight-bearing swimming time of mice by 88.57 %, reduced fatigue markers BUN, BLA, and MDA (18.47 %, 12.92 %, and 15.16 %), and enhanced liver/muscle glycogen and SOD (28.99 %, 28.57 %, and 14.47 %). The investigation into its anti-fatigue mechanism suggested that FCD enhanced GS protein expression by activating PI3K/AKT/GSK3β signaling. These findings suggest that FCD enhances anti-fatigue effects by modifying its metabolic properties and biological activity.

Abstract The lockbolt structure is essential in railway wagons, and a scientific lockbolt layout can ensure uniform load distribution, thereby preventing failure. However, current engineering lacks layout optimization methods that address multidimensional failure modes. This paper presents a new lockbolt structure layout optimization method based on submodel, parametric models, and a multi-strategy integrated NSGA-III (MSNSGA-III), adhering to the DVS EFB 3435-2 standard. This method simultaneously optimizes the number and spacing of lockbolts to prevent tensile, bearing, shear, and other static failure modes under specified load conditions. The proposed method was applied during the design phase of a container flatcar. Optimization results indicate that, compared to NSGA-III, this method achieves the best IGD and HV values across multiple complex test functions, demonstrating superior performance in solving complex Pareto front optimization problems. Additionally, the optimized lockbolt structure's safety margins increased by a maximum of 59.81%, passing the full vehicle strength test and significantly enhancing resistance to multidimensional failure modes. These results highlight the method's significant practical application value in addressing the optimization of railway wagon lockbolt structures under complex multidimensional failure modes.

Abstract Background With the development of Internet information technology, especially the impact of the sudden outbreak of the novel coronavirus disease 2019 epidemic, along with the call for “classes suspended but learning continues,” a large number of medical educators have learned and experienced online teaching. They have understood the shortcomings of traditional teaching methods. Not only the blended BOPPPS teaching mode combines the advantages of the BOPPPS teaching mode but also the online teaching platform breaks through the limitation of time and space. However, a general consensus on the effectiveness of the blended BOPPPS teaching strategy in China is lacking, and few studies use quantitative synthesis to evaluate the effectiveness of this teaching strategy. Hence, this study aimed to assess the overall effectiveness of online and offline blended BOPPPS teaching strategies in higher medical education in China compared with the lecture-based learning (LBL) teaching model. Methods Studies that blended learning with the BOPPPS model in China from January 2000 to October 2023 were searched in the Chinese and English-language online databases. We analyzed the objective and subjective scores of students and performed subgroup analysis for specialties and online teaching platforms. The data were analyzed using the Stata version 14.0 software. The quality assessment was performed using the Jadad scoring scale. Results Forty-four studies were included in this meta-analysis. Compared with the LBL mode, the blended the BOPPPS teaching mode was more effective in terms of the overall capacity [standardized mean difference (SMD) = 1.193, 95% confidence interval (CI): 0.813–1.572], mastery of medical theory knowledge (SMD = 1.090, 95% CI: 0.730–1.450), and practical skills (SMD = 1.246, 95% CI: 0.799–1.693). The analyzed questionnaire surveys indicated the positive effects of the blended BOPPPS teaching mode on classroom satisfaction, autonomous learning ability, learning interest, teamwork ability, interpersonal skills, ability to analyze and solve problems, group interaction, learning engagement, and learning strategies. Conclusions The study underscored that the blended BOPPPS teaching mode could effectively improve the comprehensive quality of students. The subjective scores also indicated that students generally preferred this novel teaching mode.

Abstract Triglyceride-Glucose Index (TyG index) and HbA1c are metabolic risk factors associated with insulin resistance (IR), which have been confirmed to be independently correlated with the incidence of hypertension. However, there is limited research specifically focusing on the interaction between these two metabolic risk factors in hypertensive populations. Currently, it remains unclear how the metabolic indicators TyG index and HbA1c affect BP control in individuals with hypertension. This study aims to investigate the value and interaction of TyG index and HbA1c in blood pressure (BP) control among hypertensive patients. The results are conducive to enhancing the effectiveness of clinical BP control for individuals with hypertension. This cohort study included 99,336 adults diagnosed with hypertension. Participants were grouped according to the median of TyG index and HbA1c. The main endpoint is inadequate BP control. Multivariable-adjusted risk ratios and multivariable Cox regression analysis were used to represent the relationship between BP control levels and metabolic risk factors. Finally, we evaluated the interaction between TyG index and HbA1c in the population with inadequate BP control. This study confirmed that TyG index and HbA1c, as metabolic risk factors, are independently associated with poor BP control (P

Objective To investigate the physicochemical and biological properties of a new calcium sulfate-based root canal sealer for deciduous teeth containing calcium sulfate hemihydrate, barium sulfate, chlorhexidine acetate, and polyethylene glycol 400 (PEG 400). Methods This study was reviewed and approved by the Ethics Committee. The calcium sulfate hemihydrate and barium sulfate powders with different mass percentages were mixed with liquid PEG 400 at a powder-to-liquid ratio of 3∶1, and chlorhexidine acetate was added to a concentration of 0.2 mg/mL according to the volume of PEG 400. The above materials were mechanically ground at 250 r/min for 24 h to obtain a calcium sulfate-based root canal sealer for deciduous teeth. The sealer was classified into different groups according to mass percentages of components. The mass percentages of components were optimized by performing time, fluidity, and radiopacity experiments, and then the pH, mass loss in vitro, and microscopic morphology of the optimal sealer were evaluated. The antimicrobial properties of the sealer were evaluated by a bacterial-material cocultivation method. The cytocompatibility of the sealer was evaluated by a CCK-8 assay and cytomorphological staining, and its biocompatibility was evaluated by a subcutaneous tissue embedding assay. Results After optimization, mass percentage of calcium sulfate hemihydrate was 80 wt%, and the mass percentage of barium sulfate was 20 wt%. The flowability and radiopacity of the sealer were in accordance with international standards. The pH stabilized between 6-7. On the 7th and 14th days, the pH in the water group was significantly greater than that in the PBS group (PP>0.05). In vitro degradation experiments, the mass loss of the sealer was approximately 15.17% during the preimmersion period, and rate of mass loss decreased after 3 weeks, reaching only approximately 8.33%. X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed that the main component of the sealer after hydration was calcium sulfate dehydrate. In bacterial growth assays and cytological tests, the sealer showed significant inhibition of the growth of E. faecalis (PPP>0.05). Both the sealer group and the control group (Vitapex and zinc oxide eugenol) caused mild inflammatory reactions in tissue sections. Conclusion In this study, a new type of root canal sealer for deciduous teeth was designed based on calcium sulfate, which has good physicochemical properties and strong antibacterial properties and meets biocompatibility requirements. This study provides an idea for the development of a new type of root canal sealer for deciduous teeth.

Abstract Quinoa (Chenopodium quinoa, 2n = 4x = 36), a super pseudocereal crop, has been introduced into China nearly 60 years. Many excellent varieties have been developed through massive selection; however, few are developed through mutagenesis breeding. In this study, the ‘Longli-4’ variety, locally cultivated in Gansu province, Northwest China, was selected for experimentation. The grains of ‘Longli-4’ were treated with ethyl methanesulfonate (EMS) at a concentration of 0.8% for 8 h. Nine plants from independent M2 families were randomly selected to investigate the mutagenesis effect of EMS on the quinoa genome. The results indicated that the single nucleotide polymorphisms (SNPs) induced by EMS were unevenly distributed across all 18 chromosomes, with an average mutation frequency of 91.2 SNPs/Mb, ranging from 4.5 to 203.5 SNPs/Mb. A significant positive correlation between the number of SNPs and chromosome length was identified through linear model analysis. Transitions from G/C to A/T were the most predominated in all variant categories, accounting for 34.4–67.2% of the mutations, and SNPs were significantly enriched in intergenic regions, representing 69.2–75.1% of the total mutations. This study provides empirical support for the application of low concentration EMS treatment in quinoa breeding.

Abstract With the rapid development of imaging technology and comprehensive treatment in modern medicine, the early diagnosis rate of breast cancer is constantly improving, and the prognosis is also improving; As breast cancer patients survive longer, the risk of developing second primary cancers increases. Since both breast and thyroid are Hormone receptor sensitive organs, which are regulated by hypothalamus pituitary target gland endocrine axis, changes in body endocrine status may lead to the occurrence of these two diseases in succession or simultaneously. This study extracted clinical data and survival outcomes of breast cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2019. After matching the case and controls with propensity scores, the selected patients were randomly split into training and test datasets at a ratio of 7:3. Univariate and multivariate COX proportional regression analysis is used to determine independent risk factors for secondary thyroid cancer and construct a column chart prediction model. Age, ethnicity, whether radiotherapy, tumor primary location, N stage, M stage were identified by Cox regression as independent factors affecting secondary thyroid cancer in patients with breast cancer patients, and a risk factor nomogram was established to predict patients’ 3 and 5 year survival probabilities. The AUC values for 3 and 5 years in the training set were 0.713, 0.707, and the c-index was 0.693 (95% CI 0.67144, 0.71456), and the AUC values for 3 and 5 years in the validation set were 0.681, 0.681, and the c-index was 0.673 (95% CI 0.64164, 0.70436), respectively.

This study aimed to assess the efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy in the management of male choledocholithiasis. A retrospective analysis was performed on the clinical data of 100 male patients diagnosed with choledocholithiasis and treated at our hospital between May 2020 and May 2022. The patients were categorized into either an experimental group (n = 50) or a control group (n = 50) based on their respective treatment modalities. The control group underwent laparoscopic cholecystectomy coupled with exploration and stone extraction from the common bile duct, while the experimental group underwent ERCP in conjunction with laparoscopic cholecystectomy. The results showed that the efficacy of these treatment approaches was compared in terms of their impact on choledocholithiasis. The stone clearance rate was significantly higher in the experimental group compared to the control group (p < 0.05), with no significant difference observed in the six-month recurrence rate (p > 0.05). However, the one-year recurrence rate was significantly lower in the experimental group (p < 0.05). Furthermore, the experimental group experienced reduced intraoperative bleeding, shorter hospital stays, and decreased operative duration compared to the control group (p < 0.05). Time to resume oral intake, passage of flatus, recovery of bowel sounds, and mobilization were all significantly shorter for the experimental group (p < 0.05). Notably, there was no significant difference in the incidence of postoperative complications between the two groups (p > 0.05). ERCP combined with laparoscopic cholecystectomy demonstrates efficacy in reducing postoperative stone recurrence, diminishing complications and patient trauma, alleviating pain, and facilitating continuous patient recovery following treatment for choledocholithiasis.

IntroductionDue to the impact of antibody-dependent enhancement and viral variation, effective vaccines or antiviral therapies remain lacking for the dengue virus (DENV). Nucleic acid drugs, particularly Vivo-Morpholinos (MOs), have emerged as a promising avenue for antiviral treatment due to their programmability and precise targeting, as well as their safety and stability.MethodIn this study, we designed and developed 10 morpho-modified (octa-guanidine dendrimer) vivo-MO molecules that target each coding gene of DENV. Subsequently, we assessed the inhibitory impact of vivo-MOs on dengue viral RNA load utilizing qRT-PCR. Furthermore, we examined the inhibitory effect on the live virus through a plaque assay and the TCID50 assay.ResultsWe found that the vivo-3′UTR molecule targeting the 3′ untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3′UTR demonstrated 99% inhibition of dengue virus RNA and the inhibition of up to 98% of the live virus. Additionally, the targeted sequence was conserved among all four DENV serotypes, and treatment with 10 μM of vivo-3′UTR resulted in a reduction of viral titers for all four DENV serotypes by over 99.99%. Additionally, we revealed that pre-treatment with vivo-3′UTR had a notable preventive effect against viral infection.ConclusionThis study screened an effective vivo-MO target drug for the treatment of dengue virus infection, demonstrating low toxicity in mammalian cell lines, and proposed a novel preventive antiviral approach.

BackgroundSurgical intervention is a crucial treatment for hepatic cystic echinococcosis. However, the choice between radical and conservative surgery remains controversial. This study aimed to compare the perioperative outcomes and hospitalization costs between radical and conservative surgery for hepatic cystic echinococcosis.MethodA retrospective cohort study was conducted on patients undergoing surgical treatment at the First People's Hospital of Kashi Prefecture from July 1, 2012, to October 1, 2023. Propensity score-matching analysis was utilized to mitigate patient selection bias between the two surgical groups.ResultOf the 434 patients included, 324 underwent conservative surgery and 110 underwent radical surgery. After propensity score-matching, 182 conservative surgery and 102 radical surgery patients were compared. Radical surgery patients experienced longer operative time, higher intraoperative blood loss, increased blood transfusion, and higher costs compared to conservative surgery patients. However, no differences were observed in short-term outcomes, including overall morbidity, death, bile leak, effusion, pulmonary infection, incision infection, intestinal obstruction, ICU stay, abdominal drainage time, and postoperative hospital stays.ConclusionThis study suggests that radical surgery is associated with greater surgical complexity and higher hospitalization costs, while it doesn't offer a significant short-term advantage. Conservative surgery may be a viable option in resource-limited settings or for patients unsuitable for complex procedures. Further research with long-term follow-up is needed to determine the optimal approach.

This study focused on examining the protection of QiShenYiQi dripping pills (QSYQ) against myocardial infarction (MI) and investigating its potential mechanisms. Ultra high performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to analyze potential active compounds of QSYQ. The targets of these compounds were predicted using an integrated in silico method and cross-referenced with relevant databases to identify associated pathways. Experimental validation was then conducted to confirm the accuracy of the systems pharmacology findings. In the end, network analysis combined with UHPLC screened 13 potential active compounds and obtained 99 targets for the intersection of potential active compounds and diseases. The enrichment analysis results indicated that the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway might be the mechanism of action of QSYQ in the treatment of MI. Experimental verification demonstrated that QSYQ could alleviate oxidative stress, promote vasodilation, and activate proteins related to the mitochondrial ATP-sensitive potassium channel (KATP) and nitric oxide (NO)-cGMP-PKG signaling pathway. This study provides insights into both the pathogenic mechanisms underlying MI and the molecular mechanisms through which QSYQ may confer protection. Given the role of PKG in regulating myocardial stiffness, it emerges as a promising therapeutic target for myocardial remodeling. We propose that the NO-cGMP-PKG and mitochondrial KATP pathways may serve as candidate therapeutic targets for the development of new interventions for MI.

Abstract Photodetectors based on 2D hetero‐bilayers can overcome the bandgap limitations of individual 2D monolayers and operate at relatively long wavelengths. However, ultra‐low light absorptions within hetero‐bilayers result in extremely weak photoresponsivity. Here, an infrared photodetector based on the MoS2/MoTe2 type‐II hetero‐bilayer is demonstrated to reach a photoresponsivity of 0.55 A W−1 at 1550 nm, well beyond energy band cut‐offs of monolayer MoS2 and MoTe2, primarily resulted from the photogating effect. Raman and photoluminescence (PL) spectroscopy reveal strong interlayer couplings in the hetero‐bilayer, and a broad PL peak around 1550 nm is observed that is ascribed to interlayer transitions of carriers. The photodetector showcases a broadband detection capability from 1100 to 1700 nm, with a peak at 1550 nm corresponding to the interlayer absorption. Electrical characterization of the hetero‐bilayer‐based field‐effect transistor and kelvin probe force microscopy reveal efficient interlayer hole transfer. The highly responsive MoS2/MoTe2 infrared photodetector offers a large photo‐gain of ≈103 and a time constant of 130 ms. The research illuminates how interlayer transitions affect 2D hetero‐bilayer‐based photodetectors and advances the utilization of layered semiconductor heterostructures.

The purpose of this study was to investigate the protective effect and underlying mechanism of orexin A on cerebral ischemia-reperfusion injury, specifically through vasodilation mediated by the hypoxia inducible factor-1α (HIF-1α)-Endothelin-1(ET-1)/endothelial nitric oxide synthase (eNOS) pathway. A model of middle cerebral artery occlusion was established in both wild-type SD rats with exogenous orexin A intervention and in orexin A transgenic rats. Neurological deficit scores and cerebral infarction areas were assessed, and ischemic cortical blood flow was monitored. Gene and protein expression levels of HIF-1α, HIF-2α, ET-1, and three types of NOS were detected using real-time RT-qPCR and Western blot analysis, respectively. Additionally, nitric oxide (NO) levels in the cortex were analyzed through biochemical detection methods. Orexin A demonstrated a protective effect by reducing cerebral infarction and improving neurological deficits, which was achieved by increasing cortical blood flow during reperfusion. This protective mechanism was associated with upregulated HIF-1α expression, downregulated ET-1 expression, upregulated eNOS expression, and increased NO production. This study demonstrates the protective effect of orexin A on cerebral ischemia-reperfusion injury, achieved by regulating the release of vasomotor substances to enhance cortical blood flow during reperfusion. These findings suggest that orexin A may represent a potential therapeutic strategy for ischemic stroke.

Background: For antiretroviral therapy (ART), drug combinations have been freely provided to people living with human immunodeficiency virus (PLWH) for treatment of acquired immunodeficiency syndrome (AIDS)in China. We have systematically analyzed the treatment results in Huzhou, Zhejiang Province. Methods: Total 724 patients with HIV antibody positive from May 2005 to March 2023 at the age of 40.4±15.4 (15-82) years were treated with free provided drug combinations, including lamivudine (3TC), efavirenz (EFV) and tenofovir (TDF), or drugs at patient's own expense, includingbictegravir (BIC), emtricitabine (FTC) and tenofovir alafenamide (TAF). CD4+ T-cell count and viral load (VL) were detected before and after HAART treatment. Results: Before and after HAART treatment, CD4+ T-cell count and viral load (VL) were measured. CD4+ T-cell count in 724 PLWH was from 269.2±178.9 to 453.8±243.3 cells/µl (p=0.0001), with 627(86.60%) cases increasing (221.0±204.6 cells/µl), 63(8.70%) decreasing (-96.0±84.1 cells/µl), 54(7.46%) cases no change. At the end of the treatment, 251(34.67%) cases were with CD4+ T-cell count>500.Viral load (VL)in 243 PLWHwas 14,474.4±62769.4 vs. 1,100.3±8513.1 copies/ml (p=0.0011), and with 181(74.49%) cases decreasing (-18,365.3±71,761.1 copies/ml), 14(5.76%) increasing (5,302.3±11,766.8 copies/ml), and 48 (19.75%) no change. Twenty-six patients died during the treatment period. There were no significant differences between results using free provided and paid drug combinations. Conclusion: The free provided drug combinations increase CD4+ T-cell count and decrease viral load in PLWH, but about one-fourth of patients are considered as treatment failure. The improvement is needed for the HAART treatment.

IntroductionBladder cancer (BCa) is a common malignancy in the urinary tract. It has high recurrence rates and often requires microscopic examination, which presents significant challenges in clinical treatment. Previous research has shown that circular TAF4B (circTAF4B) is significantly upregulated in BCa and is associated with a poor prognosis. However, the specific targets and molecular mechanisms by which circTAF4B functions in BCa are still not well - understood.MethodsIn this study, an RNA pull - down assay and mass spectrometry were utilized to identify MFN2 as a binding protein of circTAF4B. Additionally, siRNA was used to silence MFN2 to observe the amplification of the inhibitory effects of circTAF4B overexpression on cell growth and migration in BCa cells. Moreover, circTAF4B shRNA lentiviral particles were employed to study their impact on BCa progression by examining the regulation of p27 and the blocking of AKT signaling.ResultsIt was found that MFN2 is a binding protein of circTAF4B. Silencing MFN2 with siRNA enhanced the inhibitory effects of circTAF4B overexpression on cell growth and migration in BCa cells. Also, circTAF4B shRNA lentiviral particles inhibited BCa progression by upregulating p27 and blocking AKT signaling.DiscussionIn conclusion, the physical binding of circTAF4B to MFN2 is a crucial process in the tumorigenesis and progression of BCa. Targeting circTAF4B or its complexes may have potential as a therapeutic strategy for BCa diagnosis and treatment.

IntroductionIn patients with rheumatoid arthritis (RA), the increased risk of concomitant type 2 diabetes mellitus (T2D) is an important contributor to increased mortality and decreased quality of life; however, the mechanisms and pathogenetic factors remain unknown. MethodsIn this study, we aimed to assess the risk factors for T2D in patients with RA. We recruited 206 healthy controls and 488 patients with RA, 160 of whom had comorbid T2D. General clinical information, disease characteristics, and circulating lymphocyte levels detected using modified flow cytometry were collected from all participants. Logistic regression models adjusted for confounders were fitted to estimate the risk factors of T2D in patients with RA.ResultsThe incidence of RA in patients with T2D was 15.6%. Patients with RA and T2D had a longer disease duration, higher BMI, and a higher incidence of hypertension and a family history of diabetes than those with RA but no T2D. The absolute numbers of T helper 2 cell (Th2) and Regulatory T cells (Treg) decreased in patients with RA and T2D, which led to an increase in the ratios of Th1/Th2 and Th17/Treg cells. Multivariate logistic regression analysis showed that a family history of diabetes, a higher incidence of hypertension, higher neutrophil-lymphocyte ratio (NLR) levels, lower platelet-lymphocyte ratio (PLR) levels, and fewer circulating Th2 and Treg cells were associated with an increased risk of T2D in patients with RA.DiscussionThe levels of peripheral lymphocytes, especially Th2 and Treg cells, are closely related to the occurrence of T2D in patients with RA; however, the influence of body mass index (BMI), family history of diabetes, and systemic inflammation should not be ignored.

Gastric cancer (GC) is a common malignant tumour with high incidence and mortality rates worldwide. Despite current treatment modalities, including surgical resection and chemotherapy, challenges such as postoperative recurrence, metastasis and drug resistance persist. Therefore, investigating the feasibility and mechanism of traditional Chinese medicine in treating gastric cancer is crucial for discovering new anti-gastric cancer drugs or adjuvant therapies. Pachymic acid (PA) is a natural triterpenoid found in the traditional Chinese medicinal herb Poria cocos (PC) (Schw. Wolf). Recent studies have reported its inhibitory effects on various cancer cells, including liver, cervical, breast and gastric cancer. Our in vitro and in vivo experiments confirmed that PA inhibits the proliferation, migration and invasion of gastric cancer cells. The treatment of gastric cancer cells with various death inhibitors revealed that PA may suppress gastric cancer progression by inducing ferroptosis. Malondialdehyde, Fe2+, reactive oxygen species and glutathione assays were performed to validate the effects of PA on ferroptosis in gastric cancer. High-throughput sequencing combined with analysis of the TCGA database identified PDGFRB as a potential downstream target of PA. In vivo experiments indicated that the PDGFRB overexpression could counteract the antitumour effects of PA, while ferroptosis induced by the PI3K/Akt signalling pathway may play a key role in this process. This study provides initial evidence that PA, through its interaction with PDGFRB, alters the PI3K/Akt signalling pathway, leading to ferroptosis in gastric cancer cells, thus manifesting its antitumour properties. This discovery holds promise for the development of novel therapeutic strategies for gastric cancer patients.

BackgroundRheumatoid arthritis (RA) is an autoimmune disease with various subtypes. Among these, seronegative rheumatoid arthritis (SnRA), distinguished by its distinctive seronegative antibody phenotype, presents clinical diagnosis and treatment challenges. This study aims to juxtapose the immunological features of SnRA with seropositive rheumatoid arthritis (SpRA) to investigate potential mechanisms contributing to differences in antibody production.MethodsThis study included 120 patients diagnosed with RA and 78 patients diagnosed with psoriatic arthritis (PsA), comprising 41 cases of SnRA and 79 cases of SpRA. Clinical, serological, and immune data were collected from all participants to systematically identify and confirm the most pivotal immunological distinctions between SnRA and SpRA.Results(1) SpRA demonstrates more pronounced T-helper 17 cells (Th17)/Regulatory T cells (Treg) dysregulation, vital immunological differences from SnRA. (2) SpRA exhibits higher inflammatory cytokine levels than SnRA and PsA. (3) Lymphocyte subset ratios and cytokine overall distribution in SnRA close to PsA. (4) Interleukin-4 (IL-4) emerges as the central immunological disparity marker between SnRA and SpRA.ConclusionTh17/Treg imbalance is one of the vital immunological disparities between SnRA and SpRA. Interestingly, PsA and SnRA display similar peripheral blood immunological profiles, providing immunological evidence for these two diseases’ clinical and pathological similarities. Furthermore, IL-4 emerges as the central immunological disparity marker between SnRA and SpRA, suggesting its potential role as a triggering mechanism for differential antibody production.