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Objective and methods In this study, the hydrochemical method and self-organized neural network (SOM-KM) coupling method were employed to identify recharge sources and reveal the water-rich mechanism in the karst groundwater-rich area of the Changxiao karst water system in Jinan City. The contribution ratio of karst groundwater recharge sources in the karst groundwater-rich area was quantitatively calculated using the end-element mixed model. The enrichment mechanism of karst groundwater is explored by combining with topography, geological structure, stratigraphic lithology, and catchment conditions. Results The results showed that the karst groundwater in the catchment drainage area had similar water chemistry to that in the southern recharge area, the karst groundwater in the lateral runoff area, and the Yellow River, indicating a close hydraulic connection. This implies that the karst groundwater in the catchment drainage area is recharged by three sources: The southern mountain area, the karst groundwater in the lateral runoff area, and the Yellow River. The contribution ratios of the three components are 75.09%, 21.02%, and 3.89%, respectively. Carbonate rocks are widely distributed, and fissured karst is well developed in the accumulation and discharge areas, especially in the Maji-Xiaoli-Guide area. Moreover, there are abundant karst groundwater recharge sources in this area. During the runoff process of karst groundwater from southeast to northwest, it is impeded by sandstone and mudstone in the north. As a result, it accumulates in the contact zone between soluble rock and insoluble rock, thus forming impeded-type karst groundwater-rich structures. Conclusion Revealing the enrichment mechanism of karst groundwater in the Changxiao karst water system can provide scientific support for accurate calculations of recoverable resources and the protection of the springs in Jinan.

Abstract Cation separation under extreme pH is crucial for lithium recovery from spent batteries, but conventional polyamide membranes suffer from pH-induced hydrolysis. Preparation of high performance nanofiltration membranes with excellent pH-resistance remains a challenge. Here we synthesize a high performance nanofiltration membrane (1,4,7,10-Tetraazacyclododecane (TAD)−1,3,5-Tris(bromomethyl)benzene (TBMB) thin film composite membranes (TFCMs)) with excellent pH-stability through interfacial quaternization reaction between TAD and TBMB. Due to the high stability of “C-N” bonds in TAD-TBMB TFCMs, its separation performance is stable even after 70 days immersion in concentrated acid (3 M H2SO4, HNO3, or HCl) and base (3 M NaOH), which is at least 15 times more stable than benchmark commercial membranes. The membrane shows an overall separation performance (11.3 L m−2 h−1 bar−1 (LMHB), RCo2+: 97% in 2 M H2SO4) due to the size sieving and the intensified charge repulsion, outperforming many of the state-of-the-art membranes. Finally, the TAD-TBMB TFCM remains stable during 30-days continuous nanofiltration of 2 M H2SO4 and leachate (2 M H2SO4, ions: 6.2 g L−1) from spent batteries.

Abstract A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).

Abstract The heat shock transcription factor (HSF) family is one of the most widely studied transcription factor families in plants; HSFs can participate in the response to various stressors, such as heat stress, high salt, and drought stress. Based on garlic transcriptome data, we screened and identified 22 garlic HSFs. The HSF proteins of garlic and Arabidopsis can be divided into three (A, B, C) subfamilies. The phylogenetic relationship, chromosome localization, sequence characteristics, conserved motifs, and promoter analysis of the HSF family were analyzed through bioinformatics methods. RT-qPCR analysis showed that the nine selected genes had different degrees of response to heat stress. In addition, we isolated and identified a class B HSF gene, AsHSFB1, from garlic variety ‘Xusuan No.6’. Subsequently, the AsHSFB1 gene was overexpressed in Arabidopsis thaliana. Under heat stress, the germination rate and growth of wild-type plants were better than that of transgenic plants. Moreover, after heat treatment, the contents of peroxidase, catalase, and chlorophyll a and b of transgenic plants were lower, but the contents of malondialdehyde (MDA) and leaf conductivity were higher. Nitroblue tetrazolium (NBT) staining showed that the stained area of transgenic plant leaves was larger than that of the wild type. Further studies showed that AsHSFB1 overexpression inhibited the expression of related reverse resistance genes. These results indicate that AsHSFB1 might play a negative regulatory role in garlic resistance under high stress. Altogether, these findings provide valuable data for revealing the function of HSF genes and lay a foundation for the subsequent selection of heat-resistant garlic varieties.

Abstract Objective To explore the clinical efficacy of monolayer suture combined with a hem-o-lok clip during partial nephrectomy among patients with renal cell carcinoma (RCC). Methods Eighty patients with RCC underwent laparoscopic partial nephrectomy from January to October 2021. They were assigned into a control group and an intervention group, each with 40 cases using random number table. The control group received double-layer sutures on the wound, while the intervention group had single-layer sutures with a hem-o-lok clip for hemostasis. The study compared operative indexes and postoperative recovery of the two groups. Results Intraoperative bleeding and warm ischemia time in the intervention group were significantly shorter than that in the control group. There were no significant differences in operation time, drainage volume on the first day after operation, and hospital stay between the two groups. Before operation, there were no significant differences in serum creatinine and blood urea nitrogen between the two groups. However, 24 h post-operation, both groups experienced a significant increase in these levels, with the intervention group showing lower levels than the control group. Changes in glomerular filtration rate were significantly lower in the intervention group than the control group. Complication rates were similar, with 7.5% in the research group and 10.0% in the control group. Conclusion Monolayer suture combined with a hem-o-lok clip can shorten the time of warm ischemia, reduce intraoperative bleeding and the loss of normal renal parenchyma in patients undergoing laparoscopic partial nephrectomy. More studies with larger sample size are needed to confirm the results.

Objectives: The guidelines recommend fractional flow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative flow ratio (QFR) is a novel coronary angiography (CAG)-based fractional flow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. Methods: This observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis ≥50%) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR ≤0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis ≥50% (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. Results: After propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 ± 0.7 vs 1.6 ± 0.5 [P

Abstract Background To clarify the fat attenuation index (FAI) change trend of peri-saphenous vein graft (SVG) and determine the association between FAI and graft disease progression based on CCTA images. Methods Patients with venous coronary artery bypass grafts (CABGs) were consecutively enrolled in this retrospective study. In study 1, 72 patients who had undergone 1, 3, and 5 years of CCTA examinations without graft occlusion were recruited, and generalized estimation equation was used to analyze the peri-SVG FAI change trend over time. In study 2, 42 patients with graft disease progression and 84 patients as controls were propensity score-matched. Generalized linear mixed model and continuous net reclassification improvement (NRI) were used for assessing the associations with graft disease progression. Multivariable Cox regression analysis was used for assessing risk factors predicting cardiac events. Results In study 1, both the FAI of proximal right coronary artery and SVG decreased over time. In study 2, the 1-year CTA-derived FAI of grafts and graft anastomosis were independent indicators of graft disease progression at the 3-year CCTA follow-up (graft: odds ratio [OR] = 1.106; 95% confidence interval [CI] = 1.030–1.188, P = 0.006; graft anastomosis: OR = 1.170, 95% CI = 1.091–1.254, P

Abstract Background Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics. Methods We enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method. Results Twenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients. Conclusions Patients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse.

Abstract Background Lung cancer remains a leading cause of cancer-related mortality worldwide. Autotransplantation has emerged as a potential surgical intervention in select cases, with the aim of achieving curative outcomes. This case report describes a novel approach combining lung autotransplantation with postoperative chemotherapy and immunotherapy, delineating the patient's journey over a period of three years. Case presentation We report on a 37-year-old patient with stage IIIA non-small cell lung cancer (NSCLC) who underwent lung autotransplantation. Despite the complexity of the procedure, the patient had a favorable postoperative course. Adjuvant therapy included a PD-1 inhibitor and a standard chemotherapy regimen. The patient’s follow-up involved regular clinical assessment, imaging, and functional status evaluation, demonstrating a remarkable disease-free survival at the three-year mark postoperatively. Conclusion This case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer.

Abstract Covalent organic frameworks are a type of crystalline porous materials that linked through covalent bond, and they have numerous potential applications in adsorption, separation, catalysis, and more. However, there are rarely relevant reported on photochromism. Fortunately, a hydrazone-linked DBTB-DETH-COF is rapidly generated through ultrasound method. The DBTB-DETH-COF is found to exhibit reversible photochromism (at least 50 cycles) from yellow to olive in the presence of light and air, and subsequently back to the original color upon heating. In addition, the structure of DBTB-DETH-COF remains unchanged after 15 days of light illumination. Furthermore, the reason of photochromic process is discussed by electron paramagnetic resonance, X-ray photoelectron spectroscopy, electrochemistry characterizations and transient absorption measurements. The reversible photochromic DBTB-DETH-COF can be used as anti-counterfeiting ink and optical switch in the presence of air. This work expands a stable organic photochromic material and broadens the applications of COFs.

Some core designs integrate high-enriched fuel and moderator materials to enhance neutron utilization. This combination results in a broad spectrum within the system, posing challenges in resonance calculation. This paper introduces a general framework to realize resonance self-shielding treatment in broad-spectrum fuel lattice problems. The framework consists of three components. First, a new energy group structure is devised to support resonance calculation in the entire energy range and capture spectral transition and thermalization effects during eigenvalue calculation. Second, the subgroup method based on narrow approximation is selected as a universal method to perform resonance calculation. Finally, transport equations for each fissionable region are solved for neutron flux to collapse the fission spectrum. The proposed method is verified against fast, intermediate, and thermal spectrum pin cell problems and an assembly problem featuring a fast-thermal coupled spectrum. Numerical results affirm the accuracy of the proposed method in handling these scenarios, with eigenvalue errors below 154 pcm for pin cell problems and 106 pcm for the assembly problem. The verification results revealed that the proposed method enables accurate resonance self-shielding treatment for broad-spectrum problems.

Abstract Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

Remote sensing images often need to be merged into a larger mosaic image to support analysis on large areas in many applications. However, the performance of the mosaic imagery may be severely restricted if there are many areas with cloud coverage or if these images used for merging have a long-time span. Therefore, this paper proposes a method of image selection for full coverage image (i.e. a mosaic image with no cloud-contaminated pixels) generation. Specifically, a novel High-Frequency-Aware (HFA)-Net based on Swin-Transformer for region quality grading is presented to provide a data basis for image selection. Spatiotemporal constraints are presented to optimize the image selection. In the temporal dimension, the shortest-time-span constraint shortens the time span of the selected images, obviously improving the timeliness of the image selection results (i.e. with a shorter time span). In the spatial dimension, a spatial continuity constraint is proposed to select data with better quality and larger area, thus improving the radiometric continuity of the results. Experiments on the GF-1 images indicate that the proposed method reduces the averages by 76.1% and 38.7% in terms of the shortest time span compared to the Improved Coverage-oriented Retrieval algorithm (MICR) and Retrieval Method based on Grid Compensation (RMGC) methods, respectively. Moreover, the proposed method also reduces the residual cloud amount by an average of 91.2%, 89.8%, and 83.4% when compared to the MICR, RMGC, and Pixel-based Time-series Synthesis Method (PTSM) methods, respectively.

Abstract Background Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy. Methods We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs. Results Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs. Conclusion We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies.

Abstract A novel approach is proposed to probe the nature of the double charm tetraquark through the prompt production asymmetry between $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + in pp collisions. When comparing two theoretical pictures, i.e. the compact tetraquark and hadronic molecular pictures, we find that the former one exhibits a significantly larger production asymmetry, enabling the unambiguous determination of the tetraquark’s internal structure. Additionally, distinctive differences in the transverse momentum and rapidity distributions of $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + cross sections emerge, particularly at $$p_\textrm{T}\approx 2~\textrm{GeV}$$ p T ≈ 2 GeV and $$y\approx \pm 6$$ y ≈ ± 6 at a center-of-mass energy of 14 $$~\textrm{TeV}$$ TeV . The insignificant asymmetry in hadronic molecular picture is because that hadronic molecules are produced in hadronic phase, where the phase space of their constituents needs to be taken into account rigorously. Our work can be extended to the exploration of other double heavy tetraquark candidates, offering a versatile approach to advance our understanding of exotic hadrons.

Abstract Background Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Methods Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital’s cohort as well as TCGA-KIRC cohort. Results VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. Conclusions In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.

Periprosthetic femoral fractures (PPFFs) following total hip arthroplasty (THA) present a significant clinical challenge due to their increasing incidence with an aging population and evolving surgical practices. Historically, classifications were primarily based on anatomical fracture location, the stability of the implant, and bone quality surrounding the implant. We critically analyzed 25 classification systems, highlighting the emergence and adaptations of key systems such as the Vancouver classification system (VCS) and the Unified classification system (UCS), which are lauded for their simplicity and effectiveness yet require further refinement. VCS, developed in 1995, categorizes fractures based on the site, implant stability, and bone quality, and remains widely used due to its robust applicability across different clinical settings. Introduced in 2014, UCS expands the VCS to encompass all periprosthetic fractures with additional fracture types, aiming for a universal application. Despite their widespread adoption, these systems exhibit shortcomings, including the incomplete inclusion of all PPFF types and the imprecise assessment of implant stability and surrounding bone loss. These gaps can result in misclassification and suboptimal treatment outcomes. This paper suggests the necessity for ongoing improvements in classification systems to include emerging fracture types and refined diagnostic criteria, ensuring that they remain relevant to contemporary orthopedic practices and continue to facilitate the precise tailoring of treatment to patient‐specific circumstances. This comprehensive historical review serves as a foundation for future innovations in classification systems, ultimately aiming to standardize PPFF treatment and improve patient prognosis.

An improved weighted expectile average estimator for the regression coefficient has been obtained based on the covariate balancing propensity score (CBPS), when the responses of linear models are missing at random. The asymptotic normality of the proposed method has been proved, and the estimation effect of the method is further illustrated by numerical simulation.

Abstract Background Laccase (LAC) gene family plays a pivotal role in plant lignin biosynthesis and adaptation to various stresses. Limited research has been conducted on laccase genes in common beans. Results 29 LAC gene family members were identified within the common bean genome, distributed unevenly in 9 chromosomes. These members were divided into 6 distinct subclades by phylogenetic analysis. Further phylogenetic analyses and synteny analyses indicated that considerable gene duplication and loss presented throughout the evolution of the laccase gene family. Purified selection was shown to be the major evolutionary force through Ka / Ks. Transcriptional changes of PvLAC genes under low temperature and salt stress were observed, emphasizing the regulatory function of these genes in such conditions. Regulation by abscisic acid and gibberellins appears to be the case for PvLAC3, PvLAC4, PvLAC7, PvLAC13, PvLAC14, PvLAC18, PvLAC23, and PvLAC26, as indicated by hormone induction experiments. Additionally, the regulation of PvLAC3, PvLAC4, PvLAC7, and PvLAC14 in response to nicosulfuron and low-temperature stress were identified by virus-induced gene silence, which demonstrated inhibition on growth and development in common beans. Conclusions The research provides valuable genetic resources for improving the resistance of common beans to abiotic stresses and enhance the understanding of the functional roles of the LAC gene family.

Background/Aims The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Methods Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. Results FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). Conclusions FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Abstract With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, ‘Xusuan No. 6’ was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Abstract Anion exchange membrane (AEM) water electrolysis employing non-precious metal electrocatalysts is a promising strategy for achieving sustainable hydrogen production. However, it still suffers from many challenges, including sluggish alkaline hydrogen evolution reaction (HER) kinetics, insufficient activity and limited lifetime of non-precious metal electrocatalysts for ampere-level-current-density alkaline HER. Here, we report an efficient alkaline HER strategy at industrial-level current density wherein a flexible WS2 superstructure is designed to serve as the cathode catalyst for AEM water electrolysis. The superstructure features bond-free van der Waals interaction among the low Young’s modulus nanosheets to ensure excellent mechanical flexibility, as well as a stepped edge defect structure of nanosheets to realize high catalytic activity and a favorable reaction interface micro-environment. The unique flexible WS2 superstructure can effectively withstand the impact of high-density gas-liquid exchanges and facilitate mass transfer, endowing excellent long-term durability under industrial-scale current density. An AEM electrolyser containing this catalyst at the cathode exhibits a cell voltage of 1.70 V to deliver a constant catalytic current density of 1 A cm−2 over 1000 h with a negligible decay rate of 9.67 μV h−1.

Summary: Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and Gi1 protein as well as FFAR2 in complex with butyrate and Gi1 at 3.2 Å and 3.3 Å resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family.

Potassium (K) deficiency in plants can lead to metabolic disorders and growth retardation. Currently, nearly 50% of the arable land in China is experiencing a K resource deficit, significantly hindering the development of the apple industry. Resveratrol (Res), a phytoalexin, has been extensively reported to enhance plant resistance against various abiotic stresses. However, there have been no reports on the response of Res to K+ deficiency stress in apples. This study aims to investigate the effect of exogenous Res on the K+ deficiency tolerance of Malus hupehensis. The results demonstrated that applying 50 μM of exogenous Res could enhance the tolerance of M. hupehensis to K+ deficiency stress. Compared to non-Res treatments, external application of Res alleviated leaf chlorosis and improved root growth in apple seedlings. Additionally, it increased antioxidant enzyme activity, thereby reducing the production of reactive oxygen species induced by K+ deficiency stress. Res also regulated proline and soluble sugar content to maintain osmotic balance. Moreover, Res helped maintain the balance of mineral element contents in apple seedlings and the normal K+: Na+ ratio by enhancing the influx of K+. Furthermore, exogenous Res regulated the expression of related kinase genes, promoting Ca2+ signal transduction in response to K+ deficiency stress and inducing the expression of K+ transport genes to enhance K+ absorption, thus supporting normal plant growth. In conclusion, this study provides a theoretical basis for the application of exogenous Res to alleviate K+ deficiency stress in apples.

BackgroundIntrinsic capacity (IC), as a comprehensive measure of an individual’s functional ability, has gained prominence in the framework for healthy aging introduced by the World Health Organization (WHO). As internet usage continues to integrate into daily life, it is imperative to scrutinize the association between internet use and IC to effectively promote healthy aging among the middle-aged and older population. ObjectiveThis study aimed to investigate whether daily internet use in middle-aged and older adults delays or accelerates the decline in IC. MethodsParticipants included in the China Health and Retirement Longitudinal Study (CHARLS) comprised individuals aged ≥45 years residing in China. We analyzed 4 years of CHARLS data from the first wave (May 2011-March 2012) to the third wave (July 2015-January 2016). Data from the first and third waves were used for longitudinal studies. Self-reported data encompassed internet use, frequency of use, and demographic baseline characteristics. In addition, the IC evaluation involved physical examination and blood test data. Initially, linear regression was used to assess the relationship between daily internet use and IC, followed by regression splines to explore potential nonlinear associations. Subgroup and sensitivity analyses were used to investigate the heterogeneity of IC in specific conditions and the robustness of our results. Mediation effect analysis was conducted to identify the factors that mediate the relationship between daily internet use and IC, focusing on social participation, physical activity, and health status. ResultsAmong the 12,826 participants included in the longitudinal analyses, 12,305 (95.9%) did not use the internet, while 521 (4.1%) reported daily internet use with a mean age of 52.62 (SD 7.67) years. After adjusting for demographic variables, socioeconomic factors, lifestyle behaviors, and health conditions and examining the impact of daily internet use and frequency on changes in IC, our findings indicated important associations. Specifically, daily internet use is significantly linked to a slower decline in IC over time (marginal effect 1.58, 95% CI 1.03-2.12; P

Maize (Zea mays L.) fertilizer nitrogen (N) recovery efficiency (FNRE) shows regional differences in China, and is more strongly affected by soil properties than by climate. However, how soil factors regulate maize FNRE is poorly understood. Herein, 15N tracer pot experiments combined with absolute microbial quantification sequencing were conducted using eight soils covering the main maize cropping systems from northern to southern China. The aim was to elucidate which soil factors affect maize FNRE and identify their optimal range for maximizing FNRE while minimizing N loss. Our results show that soil pH, soil organic matter (SOM), and clay and sand contents were the key factors affecting maize biomass and FNRE across the eight tested soils. Maize biomass and FNRE had parabolic relationships with soil pH, SOM, clay, and sand contents, whereas N loss displayed the opposite trend. The highest maize biomass and FNRE and lowest fertilizer N loss were in the soils with pH of 6.50–6.62, SOM level of 35.25–46.90 g kg−1, clay content of 41.12 %–44.42 %, and sand content of 17.71 %–23.41 %. Under these soil conditions, maize growth and soil N retention capabilities exhibited a high degree of coordination. Bacterial communities differed significantly among the soils, sharing the same soil drivers as maize biomass and FNRE. The abundance of N cycling genes (nasA, narI, narJ, nrfA, and nrfB) involved in dissimilatory nitrate reduction to ammonium (DNRA) was positively correlated with FNRE and negatively correlated with fertilizer N loss, suggesting that DNRA may contribute to soil N retention and enhance FNRE by affecting substrates for nitrification and denitrification. Our study demonstrates that soil pH, SOM, and texture are three key factors driving FNRE variation in maize cropping systems across China, and high microbial-driven DNRA may account for maximum maize FNRE. These findings highlight the importance of tailored FNRE enhancement strategies based on soil characteristics.

The glycolytic enzyme cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GAPC3) is involved in multiple biological processes in plants, including transcriptional regulation, and material metabolism. However, the relationship between OsGAPC3 and the quality traits of rice is poorly understood. Here we identify OsGAPC3 mutations that enhance the protein content and grain nutritional quality of rice by regulating the OsAAP6 gene expression. The number and volume of type-II protein bodies in the endosperm of the OsGAPC3 mutants, and GPC increase significantly. We report significant increases in chalkiness area and degree, and decreases for starch content, gel consistency, and taste value. Results of proteomic detection and analysis reveal that OsGAPC3 affects the major storage substances (proteins and starch) metabolism in rice, and the accumulation of proteins and starch in the endosperm. Additionally, the OsGAPC3 mutation significantly decreases the rice-seedling salt tolerance. Therefore, OsGAPC3 affects multiple quality traits of rice, participates in regulating rice-seedling salt-stress response. These data can be used to design better-quality and stronger salt-resistant rice varieties.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Global warming has increased the risk of meteorological drought and associated hazards. Based on daily data from 35 meteorological stations in the Songhua River Basin (SRB) collected from 1960 to 2019, this study applied the standardised precipitation evapotranspiration index (SPEI) and used the ensemble empirical mode decomposition (EEMD) method and Pettitt's mutation test to perform a partitioned segmentation analysis of the multi-temporal and spatial variations in the meteorological droughts affecting the basin in terms of frequency and intensity, and discussed the relationship between the atmospheric circulation index and meteorological drought. The results showed that the overall meteorological drought trends shifted from a drought to a humid trend from 1960 to 2019. The drought in the basin had periods of 3, 6.7, 15, and 30 years, with mutation points in 1968, 1980, 1997, and 2012. The drought trend in Regions I and IV of the entire basin was enhanced, while that in Regions II, III, and V was weakened. Drought in the basin was strongly influenced by the Arctic Oscillation (AO) and Southern Oscillation Index (SOI). HIGHLIGHTS The SRB shifted from a drought trend to a wet trend from 1960 to 2019.; High-frequency and high-intensity drought areas are mainly distributed in Regions I and IV.; Drought in the basin is greatly influenced by AO and SOI.;

Abstract A facile and environmentally friendly ion exchange-assisted surface passivation (IASP) strategy is presented for synthesizing red emitting Mn4+-activated fluoride phosphors. A substantial, pristine Mn4+-free shell layer, applied as a coating to Mn4+ doped potassium fluorosilicate K2SiF6:Mn4+ (KSFM) phosphors, enhances both water resistance and luminescence efficiency. The stability test of fluoride in water at ambient temperature and boiling water demonstrates that IASP-treated KSFM phosphors are highly water resistant. Furthermore, both the negative thermal temperature (NTQ) fitting results and the photoluminescence (PL) decay confirm that the IASP process effectively passivates surface defects, leading to enhanced luminescence performance. The maximum internal quantum yield (QYi) of the IASP-KSFM phosphor is 94.24%. A white LED realized a high color rendering index (CRI) of 93.09 and luminous efficiency (LE) of 149.48 lm/W. This work presented a novel technique for the development of stable fluoride phosphors and has the potential to increase the use of KSFM phosphors in plant supplementary lighting systems and white light-emitting diodes.

Abstract Background To date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method. Methods Fourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up. Results Segment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P

The purpose of this paper is to evaluate the effect of different exercise therapy on patients with chronic neck pain. By searching PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data and other databases, we screened the literatures that met the inclusion criteria until June 2022. RCT bias risk assessment tool recommended in Cochrane manual was used to evaluate the literature quality, and Stata16.0 software was used for mesh meta-analysis. A total of 76 studies, 12 exercise therapies and 5219 participants were included. In terms of pain, Pilates [MD ​= ​−2.71,95%CI (−3.87, −1.55), P ​= ​0.000] had the most significant effect. Second training for the stability of [MD ​= ​-2.39, 95 ​% CI (−3.14, −1.64), P ​= ​0.000) and VR [MD ​= ​−2.35, 95 ​% CI (−3.6, −1.11), P ​= ​0.000). In terms of functional indexes, respiratory training [MD ​= ​−16.31,95%CI (−28.52, −4.1), P ​= ​0.009] had the most significant effect. Secondly for muscle energy technology [MD ​= ​−7.47, 95 ​% CI (−12.37, −2.58), P ​= ​0.003) and aerobic training [MD ​= ​−7.36, 95 ​% CI (−12.56, −2.16), P ​= ​0.006]. Current evidence shows that Pilates, stability training and virtual reality training are the most effective in pain intervention, muscle energy technology and comprehensive exercise training are outstanding in helping functional recovery, suggesting that appropriate exercise therapy should be implemented according to the symptoms of patients to achieve the best treatment effect.

Study region: The South-to-North Water Diversion Eastern Route Project section from the Nansihu-Dongpinghu pumping station cluster.Study focus: An integrated framework for prediction and sensitivity analysis of water levels in front of pumping stations is proposed to obtain more accurate predictive surrogate models and to simplify surrogate model inputs. The results show that among the three different water transport models, the Firefly-Support Vector Machine model has a smaller mean absolute error (0.85). The Firefly-Support Vector Machine model is more suitable for water level prediction than other models. The water level in front of the target pumping station and the t-ahead flow were the most sensitive parameters, and the longer the foresight period, the higher the importance.New hydrological insight for the region: Three water transportation modes are proposed according to the characteristics of regional hydrological connectivity in the long-distance water transportation system. This enables the water level prediction surrogate model to adapt to the complex connectivity of pumping stations and lakes in the region, improving the accuracy of water level prediction. Subsequently, the parameter sensitivity of the water level prediction surrogate model for each water transport mode was also tested.

Abstract The management of dysfunctional intestinal epithelium by promoting mucosal healing and modulating the gut microbiota represents a novel therapeutic strategy for inflammatory bowel disease (IBD). As a convenient and well‐tolerated method of drug delivery, intrarectal administration may represent a viable alternative to oral administration for the treatment of IBD. Here, a biomimetic supramolecular assembly of hyaluronic acid (HA) and β‐cyclodextrin (HA‐β‐CD) for the delivery of the C domain peptide of insulin‐like growth factor‐1 (IGF‐1C), which gradually releases IGF‐1C, is developed. It is identified that the supramolecular assembly of HA‐β‐CD enhances the stability and prolongs the release of IGF‐1C. Furthermore, this biomimetic supramolecular assembly potently inhibits the inflammatory response, thereby restoring intestinal barrier integrity. Following HA‐β‐CD‐IGF‐1C administration, 16S rDNA sequencing reveals a significant increase in the abundance of the probiotic Akkermansia, suggesting enhanced intestinal microbiome homeostasis. In conclusion, the findings demonstrate the promise of the HA‐based mimicking peptide delivery platform as a therapeutic approach for IBD. This biomimetic supramolecular assembly effectively ameliorates intestinal barrier function and intestinal microbiome homeostasis, suggesting its potential for treating IBD.

BackgroundThe approval of eslicarbazepine acetate (ESL) by the Food and Drug Administration (FDA) in 2013 marked an advancement in the treatment of adult patients with partial-onset seizures. However, there still remains a paucity of real-world studies regarding the adverse events (AEs) associated with this compound. The principal aim of the present study was to scrutinize ESL-related AEs by leveraging data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsBy extracting all available data since the FDA approval of ESL (2013Q4-2024Q1), disproportionality analysis was performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithms. AE signals that simultaneously met the requirements of all four algorithms were identified as significant positive signals. Demographic information, time of onset and gender-specific signal detection were also examined. In addition, a special screening process for designated medical events (DME) was implemented to focus on the evaluation and comparison of safety signals within DME and System Organ Classification (SOC) level, as well as SMQ (Standardised MedDRA Queries) level. Stratified analysis by logistic regression is employed to examine the variations across different gender (male and female) and age groups (65 years old).ResultsA total of 5,719 AE reports and 1,907 reported cases were obtained. ESL related AEs were identified in relation to 27 SOCs, among which the significant positive SOCs were nervous system disorders, injury poisoning and procedural complications, etc. There were 86 severely disproportional preferred terms that complied with the four algorithms. Most AEs occurred within the first month after treatment. According to the 86 valuable positive signals with DME screening results, 3 signals of dermatitis exfoliative, stevens-johnson syndrome, drug reaction with eosinophilia and systemic symptoms were consistent with PT signals on the DME-list, with the 3 PTs focusing on skin and subcutaneous tissue disorders and hypersensitivity. Males are more commonly affected by seizures than females. Seizures, hyponatremia, and confusional states were more frequently observed in the elderly population, while aggression, irritability, DRESS (drug reaction with eosinophilia and systemic symptoms), and abnormal behavior were found to be more common in the pediatric population. Both the children and elderly groups exhibited a higher proportion of agitation than the adult group.ConclusionOur research enhances the safety and tolerability profile of ESL, but the clinical use of ESL should be noticed and avoided in relation to AEs since it raises the risk of dermatitis exfoliative, stevens-johnson syndrome. Particular attention should be paid to DRESS in children and hyponatremia in the elderly.

Abstract A stable and highly active core‐shell heterostructure electrocatalyst is essential for catalyzing oxygen evolution reaction (OER). Here, a dual‐trimetallic core‐shell heterostructure OER electrocatalyst that consists of a NiFeWS2 inner core and an amorphous NiFeW(OH)z outer shell is designed and synthesized using in situ electrochemical tuning. The electrochemical measurements of different as‐synthesized catalysts with a similar mass loading suggest that the core‐shell Ni0.66Fe0.17W0.17S2@amorphous NiFeW(OH)z nanosheets exhibit the highest overall performance compared with that of other bimetallic reference catalysts for the OER. Additionally, the nanosheet arrays were in situ grown on hydrophilic‐treated carbon paper to fabricate an integrated three‐dimensional electrode that affords a current density of 10 mA cm−2 at a small overpotential of 182 mV and a low Tafel slope of 35 mV decade−1 in basic media. The Faradaic efficiency of core‐shell Ni0.66Fe0.17W0.17S2@amorphous NiFeW(OH)z is as high as 99.5% for OER. The scanning electron microscope, transmission electron microscope, and X‐ray photoelectron spectroscopy analyses confirm that this electrode has excellent stability in morphology and elementary composition after long‐term electrochemical measurements. Importantly, density functional theory calculations further indicate that the core‐shell heterojunction increased the conductivity of the catalyst, optimized the adsorption energy of the OER intermediates, and improved the OER activity. This study provides a universal strategy for designing more active core‐shell structure electrocatalysts based on the rule of coordinated regulation between electronic transport and active sites.

Background: The real-world clinical impact of mNGS on BALF in the respiratory intensive care unit (RICU) is not yet fully understood. Methods: We investigated the clinical impact of mNGS on BALF samples obtained from 92 patients admitted to the RICU over a 2-year period. We utilized both mNGS and culture methods to evaluate the effectiveness of mNGS in diagnosing pulmonary infections. The clinical impact of mNGS were evaluated by the clinician committees. Results: Among the 92 diagnosed patients, 78 cases (84.7 %) were determined to have infectious diseases caused by pathogenic microorganisms, and the bacterial infections constituted the most prevalent diagnostic category. For mixed infection, the most common type was the Pneumocystis jironecii and cytomegalovirus co-infection. The mNGS results had a positive impact on the clinical management of 43 cases (46.7 %). Moreover, 19 cases (44.2 %) of positive clinical impacts were solely based on new diagnoses made possible by mNGS results. These new diagnoses were particularly helpful for identifying rare pathogens, which could not be detected by conventional diagnostic methods. Conclusions: The BALF mNGS has a positive real-world impact in RICU. Clinician committee play a critical role in ensuring the appropriate use of mNGS.

Abstract Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell‐derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO‐generating proteolipid nanovesicles (PLV‐NO) are designed that recapitulate the cell‐mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO‐generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV‐NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet‐based PLV‐NO (pPLV‐NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)‐based PLV‐NO (ePLV‐NO) exhibits suppression of thrombosis when modified onto a locally transplanted small‐diameter vascular graft (SDVG). The versatile design of PLV‐NO may enable a promising therapeutic option for various vascular injury‐evoked cardiovascular diseases.

Background: To investigate the search for an Iliac-Talar Grafts on the iliac bone that is morphologically matched to a multiplanar injury lesion of the talus; while utilizing a bone-harvesting guide to ensure precise positioning of the Iliac-Talar Grafts. Methods: A total of twenty-two cases with both talar CT data and iliac CT data were collected from January 2019 to June 2023. One case each of talar deformity injury and bone disease were excluded, resulting in a selection of 20 cases. The medial and lateral target repair areas of the talus were formulated, and virtual surgery was performed by using digital orthopedic technology to locate an iliac-talar restoration on the iliac bone that matched the morphology of the multiplanar injury lesion of the talus. 3D chromatographic deviation analysis was used to assess the accuracy of Iliac-Talar Grafts in terms of morphometric matching and positioning, while personalized iliac bone extraction guides were designed to ensure accurate positioning of the Iliac-Talar Grafts. Results: The best fitting point for repairing the medial talar lesion is determined to be medial to the anterior iliac crest, specifically 2.935 ± 0.365 cm posterior to the anterior superior iliac spine, and 2.550 ± 0.559 cm anterior to the valgus-iliac crest point (VICP). Similarly, for the repair of the lateral talar lesion, the ideal position is found to be lateral to the posterior iliac crest, approximately 2.695 ± 0.640 cm posterior to the valgus-iliac crest point (VICP). Utilizing bone extraction guides enables precise positioning for iliac bone extraction. Conclusion: This study utilizes virtual surgery, 3D chromatographic deviation analysis, and guide plate techniques in digital orthopedics to precisely locate the Iliac-Talar Graft on the iliac bone, matching the morphology of the talar lesion; it provides a new solution for cutting the iliac bone implant that matches the the multifaceted talar lesion to be repaired.

Objectives Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. Results A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training ( P < 0.0001), testing ( P = 0.016), and total ( P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. Conclusion The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.

BackgroundFerroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators.Methods and resultsThe expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA.ConclusionThe ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

BackgroundTo investigate the relationship between the Scottish inflammatory prognostic score (SIPS), treatment-related adverse events (TRAEs), and prognostication in patients with neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESCC).MethodsA retrospective investigation was carried out on 208 ESCC patients treated with NICT. The relationships between the SIPS, TRAEs, and prognosis [disease-free survival (DFS) and overall survival (OS)] were analyzed.ResultsThe patients, comprising 62 (29.8%) cases of SIPS0, 103 (49.5%) cases of SIPS1, and 43 (20.7%) cases of SIPS2, were categorized into three groups based on SIPS. Among patients with SIPS2, the oldest age (P=0.006), lowest BMI (P=0.001), longest tumor length (P=0.001), most advanced ypT stage (P=0.014), and ypN stage (P

To investigate the parameter characteristics of permanent magnet synchronous motor (PMSM) speed sensorless vector control system and capture the noise matrices quickly and accurately in the speed estimation process of the extended Kalman filter for PMSM, The recursive least square method with forgetting factor is proposed to determine the actual parameters of the system, and then a new variable-scale chaotic particle swarm optimization (VCPSO) algorithm is put forward to accurately obtain the system noise matrix and the measurement noise matrix. The simulation results show that noise matrix optimization of extended Kalman filter by employing VCPSO algorithm under actual motor parameters is better than those employing standard PSO or chaotic PSO algorithms with faster speed and higher accuracy.