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Four new wood-inhabiting fungi viz. Phanerochaete castanea, P. citrinoalba, P. citrinorhizomorpha, and P. wuyiensis spp. nov. – are proposed based on a combination of morphological features and molecular evidence. Phanerochaete castanea is characterized by soft coriaceous basidiomata detachable from the substrate, becoming reddish brown in KOH, subulate cystidia with an obtuse apex. Phanerochaete citrinoalba is characterized by the coriaceous basidiomata with smooth, cracking hymenial surface, sterile margins with yellowish to whitish rhizomorphs, a monomitic hyphal system, generative hyphae mostly with simple septa and occasionally with clamp connections at basal hyphae. Phanerochaete citrinorhizomorpha is characterized by soft coriaceous basidiomata with a salmon to peach hymenial surface, a sterile margin with yellowish rhizomorphs, simple septate generative hyphae, and clavate to subfusiform or subulate cystidia with an obtuse apex. Phanerochaete wuyiensis is characterized by membranaceous basidiomata with smooth or locally tuberculate hymenial surface and the whitish rhizomorphs, generative hyphae with both simple septa and clamp connections at basal hyphae, cystidia projecting above hymenium. DNA sequences of the ITS and LSU markers of the studied samples were generated, and phylogenetic analyses were performed with Maximum Likelihood and Bayesian Inference methods. The phylogenetic tree inferred from the concatenated ITS+nLSU dataset highlighted the placement of the four new species in the genus Phanerochaete (Phanerochaetaceae, Polyporales). Phylogenetically related and morphologically similar species to these four new species are discussed. Furthermore, an identification key to accepted species of Phanerochaete in China is given.

Abstract Background Studies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets. Methods Premature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort. Feces samples were collected on postnatal days 1, 3, and 5. Premature infants were divided into normal, mild IVH, and severe IVH groups based on cranial ultrasound. 16S rRNA amplicon sequencing technology was used to determine the fecal microbiota, and the results were analyzed. Results Thirty-eight premature infants were enrolled. There was a significant difference in alpha and beta diversity among the three groups. The relative abundance of E. coli and A. muciniphila was different among the three groups. Further random forest analysis indicated that S. lutetiensis, L. mirabilis, and N. macacae can effectively distinguish premature infants with IVH. Finally, the phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) functional gene analysis predicted significant differences in energy metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and membrane transport between normal and severe IVH groups. Conclusions The gut microbiota in the early postnatal period of premature infants is closely associated with the IVH status. As age increases, the differences in gut microbiota of premature infants with different degrees of IVH continue to increase, and the trend of changes with severity of IVH becomes more and more obvious. E. coli, A. muciniphila, S. lutetiensis, L. mirabilis, N. macacae, G. haemolysans, and S. oralis can effectively distinguish between IVH infants and normal premature infants. The results indicate that gut microbiota is expected to provide effective therapeutic targets for the diagnosis and treatment of IVH.

Abstract Objectives Hepatocyte nuclear factor 4α (HNF4α) is a key regulator of hepatocyte function and has a strong therapeutic effect on hepatocellular carcinoma (HCC) by inducing the differentiation of hepatoma cell into hepatocytes. Our previous study showed that Tribbles homolog 3 (TRIB3) directly interacts with and promotes the degradation of HNF4α in non-alcoholic fatty liver disease (NAFLD). Disrupting the TRIB3–HNF4α interaction by a cell-permeating peptide, called P-T3H2, stabilized HNF4α protein. This study aimed to assess the anti-tumor impact of P-T3H2 in HCC. Methods The expression of TRIB3 and HNF4α was evaluated using western blot and immunohistochemistry (IHC). Hepatic functions and cellular senescence of HCC cells were evaluated through periodic acid-Schiff (PAS) staining, acetylated low-density lipoprotein (ac-LDL) uptake and senescence-associated β-galactosidase (SA-β-gal) activity staining, respectively. RNA-Seq analysis was performed to identify differentially expressed genes in Huh7 cells treated with P-T3H2. The impact of P-T3H2 on HCC malignancy was assessed in vitro and in vivo. Results TRIB3 exhibited a negative correlation with HNF4α in both human and mouse HCC tissues. The administration of P-T3H2 significantly inhibited the malignancy of HCC cells. Additionally, P-T3H2 stabilized HNF4α protein and facilitated the restoration of hepatic functions and the cellular senescence in HCC cells. RNA-Seq analysis demonstrated that P-T3H2 enhanced the transcriptional activity of HNF4α in HCC. Furthermore, P-T3H2 effectively suppressed the carcinogenesis and progression of HCC in mice. Conclusion P-T3H2 suppressed HCC progression through the stabilization of HNF4α protein and may be a promising therapeutic candidate for clinical application in the treatment of HCC.

Abstract Purpose (1) To determine the clinical outcomes following revision arthroscopy for patients with hip synovial chondromatosis (SC), and (2) to compare the clinical outcomes between patients undergoing revision hip arthroscopy and primary hip arthroscopy. Methods Patients undergoing hip arthroscopy between December 2014 and January 2021 was reviewed. Patients treated for SC and confirmed by postoperative pathology were included. Exclusion criteria were age less than 18 years old, hip osteoarthritis (Tönnis grade > 1), history of autoimmune disease, avascular necrosis, and Legg–Calve–Perthes disease. Patients undergoing revision surgery were included in the revision group, while those undergoing primary surgery were matched in a 1:4 ratio and included in the primary group. Preoperative and postoperative patient-reported outcome (PRO) scores including Visual Analog pain Scale (VAS), modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and international Hip Outcome Tool, 12-component form (iHOT-12) were collected and compared. The PROs and percentage of achieving minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) of mHHS, iHOT-12, and NAHS were compared between the two groups. Results A total of 12 patients were included in the revision group, while 48 patients were included in the primary group. No significant difference was found in baseline characteristics (all with P > .05). No significant difference was found in the arthroscopic findings and procedures (all with P > .05). Both groups presented significant improvement of postoperative PROs compared to the preoperative PROs (all with P .05). Postoperatively, the revision group presented inferior VAS (P = .007), mHHS (P = .007), iHOT-12 (P = .004), and NAHS (P = .028), as well as lower rate of achieving MCID of NAHS (P = .038), and PASS of mHHS (P = .003) compared to the primary group. Conclusion Patients undergoing revision arthroscopy for hip SC presented favorable clinical outcomes at minimum of 2-year follow-up, although the postoperative PROs, rate of achieving MCID, and PASS were lower compared to patients undergoing primary arthroscopy. Level of Evidence: III.

Abstract The transient receptor potential melastatin (TRPM) channel family has been previously implicated in various diseases, including those related to temperature sensing, cardiovascular health, and neurodegeneration. Nowadays, increasing evidence indicates that TRPM family members also play significant roles in various types of cancers, exhibiting both pro- and anti-tumorigenic functions. They are involved in tumor cell proliferation, survival, invasion, and metastasis, serving as potential diagnostic and prognostic biomarkers for cancer. This paper begins by describing the structure and physiological functions of the TRPM family members. It then outlines their roles in several common malignancies, including pancreatic, prostate, colorectal, breast, brain cancer, and melanoma. Subsequently, we focused on investigating the specific mechanisms by which TRPM family members are involved in tumorigenesis and development from both the tumor microenvironment (TME) and intracellular signaling. TRPM channels not only transmit signals from the TME to regulate tumor cell functions, but also mediate extracellular matrix remodeling, which is conducive to the malignant transformation of tumor cells. Importantly, TRPM channels depend on the regulation of the inflow of various ions in cells, and participate in key signaling pathways involved in tumor progression, such as Wnt/β-catenin, MAPK, PI3K/AKT, p53, and autophagy. Finally, we summarize the current strategies and challenges of targeting TRPM channels in tumor treatment, and discuss the feasibility of combining targeted TRPM channel drugs with cancer immunotherapy.

Abstract The virtual power plant integrating the flexible resources in the distribution network can provide additional adjustment capacity for the auxiliary services of distribution network. However, the actual internal situation of distribution network including insufficient adjustable capacity of energy storage, unreasonable power allocation, and voltage overrun leads to the difficulties in optimization scheduling. Therefore, this paper proposes a power allocation optimization strategy of distributed electricity‐H2 virtual power plants (EHVPPs) with aggregated flexible resources. Specifically, a distributed EHVPP division method based on the granular K‐medoids clustering algorithm is proposed to realize the independent autonomy and coordinated interaction between EHVPPs, and in order to quantify the operation and regulation capacity of distributed EHVPPs, an aggregation approach of regulating feasible domains of flexibility resources based on the improved zonotope approximations is developed. Moreover, a power allocation strategy based on the flexibility weight factor is proposed to handle the calculated minimum deviation between the total active output of PV and the dispatching power command, realizing the self‐consistency of distributed EHVPPs. Comparative studies have demonstrated the superior performance of the proposed methodology in economic merits and self‐consistency efficiency.

Objective Thoracic spinal stenosis (TSS) surgeries necessitate a substantial amount of allogeneic blood resources. However, the efficacy of preoperative autologous blood donation (PABD) in TSS surgery has not been clearly evaluated. Therefore, we aimed to evaluate the efficacy of PABD for TSS surgery. Methods This study is a retrospective study. Totally 397 patients who underwent TSS surgeries at our institution from January 2019 to June 2023 were included. Propensity score matching (PSM) was used to make the PABD and Non‐PABD groups comparable at baseline. Regarding outcome measures, the incidence and amount of allogeneic blood transfusion, changes in postoperative hemoglobin and hematocrit levels, occurrence of postoperative complications, medical costs, drainage time, length of hospital stay, and postoperative neurological function were analyzed. The outcomes were compared between the matched PABD (n = 79) and Non‐PABD (n = 79) groups. Univariate analysis methods were used for statistical analysis, including independent samples t‐test, Wilcoxon rank‐sum test, and chi‐square test. Results The incidence of allogeneic blood transfusion (8.9% vs. 25.3%, p = 0.006) and volume of intraoperative red blood cell (RBC) transfusion (10.12 ± 54.52 vs. 122.78 ± 275.00 mL, p

Intramuscular fat (IMF) content influences various meat quality traits, including tenderness, flavor, juiciness and nutritional value. This study aimed to investigate the effects of dietary inositol supplementation on meat quality, metabolic profiles, and gut microbiota composition of finishing pigs. A total of 144 finishing pigs (initial body weight 70.41 ± 0.78 kg) were randomly divided into control, 0.075%, 0.15%, and 0.3% inositol groups. The data showed that inositol increased backfat thickness at the 6th to 7th rib and 10th rib, IMF content, and improved tenderness (P ≤ 0.05, n = 8). Paralleling an increase in fat deposition, 0.3% inositol also increased the protein level of PPARγ in the subcutaneous fat (P ≤ 0.05) and longissimus thoracis (LT) muscle (P = 0.062). Inositol elevated the content of amino acids in LT muscle and enhanced amino acid metabolism of finishing pigs, including lysine degradation, tyrosine metabolism, and arginine and proline metabolism. The 16S ribosomal RNA (rRNA) sequencing showed that 0.3% inositol supplementation altered the profiles of microbes in the colon, particularly decreasing the abundance of Firmicutes (P

Left ventricular-arterial coupling (VAC) is essential for understanding both cardiovascular physiology and pathophysiology. Traditionally assessed through invasive techniques, recent advancements have introduced noninvasive methods that employ imaging modalities and physiological parameters to evaluate ventricular pressure, volume, and arterial load characteristics. This review examines commonly used noninvasive VAC assessment methods, including echocardiographic single-beat method, myocardial work, wave intensity, the ratio of pulse wave velocity to global longitudinal strain, and imaging-based pressure-volume loops. These methodologies have demonstrated potential in clinical applications, such as evaluating cardiac function, personalizing treatment plans, monitoring therapeutic effects, and assessing prognosis. The incorporation of advanced imaging and computational techniques is anticipated to further enhance the accuracy and clinical relevance of VAC assessment in the management of cardiovascular diseases.

ABSTRACT. Background:. T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear. Methods:. Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study. Results:. The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions:. Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Abstract Hepatocellular carcinoma metastasis occurs mainly in the portal vein and lymph node metastasis, and is the main cause of patient death. However, the cellular origins and driving mechanisms of hepatocellular carcinoma metastasis have not been elucidated. In this study, we found that different tumor metastasis samples originated from different branches of the primary tumor subclone. A large number of sequence data confirmed the correlation between tumor metastasis index and metastasis and prognosis. Patients with a high index generally had a poor prognosis and abnormal metabolic function. Finally, we recommended a candidate therapy for each metastatic direction. This study explains the cellular origin and underlying mechanisms of hepatocellular carcinoma metastasis at the single-cell level and identifies drugs for its targeted therapy. It also provides a new research idea for the study of hepatocellular carcinoma metastasis and early identification of cancer metastasis from cellular resolution.

Abstract Human adenoviruses (HAdVs) are highly contagious and have significant clinical implications in the pediatric population. In the present study, we employed a combination of long-read sequencing and short-read sequencing to accurately reconstruct 32 genomes of HAdVs. The phylogenetic analyses based on the whole genome and genes revealed distinct sub-clusters within HAdV-B and -E. For HAdV-C, the phylogenetic trees constructed from hexon, fiber, and E3 gene sequences consistently matched the whole-genome phylogeny, reflecting the high sequence diversity in these regions. Notably, in regions with high sequence diversity, we observed a higher number of recombination breakpoints and lower GC content. Additionally, the E4 gene region of HAdV-C exhibited a Ka/Ks ratio > 1, indicating that positive selection may be driving the fixation of advantageous mutations. These genetic characterization analyses are crucial for enhancing future surveillance of HAdVs, facilitating a more strategic and proactive approach to monitoring their evolution, diversity, and epidemiological trends.

Abstract Quantum sensors based on solid-state defects, in particular nitrogen-vacancy (NV) centers in diamond, enable precise measurement of magnetic fields, temperature, rotation, and electric fields. Cavity quantum electrodynamic (cQED) readout, in which an NV ensemble is hybridized with a microwave mode, can overcome limitations in optical spin detection and has resulted in leading magnetic sensitivities at the pT-level. This approach, however, remains far from the intrinsic spin-projection noise limit due to thermal Johnson-Nyquist noise and spin saturation effects. Here we tackle these challenges by combining recently demonstrated spin refrigeration techniques with comprehensive nonlinear modeling of the cQED sensor operation. We demonstrate that the optically-polarized NV ensemble simultaneously provides magnetic sensitivity and acts as a heat sink for the deleterious thermal microwave noise background, even when actively probed by a microwave field. Optimizing the NV-cQED system, we demonstrate a broadband sensitivity of 576 ± 6 fT/ $$\sqrt{{{{\rm{Hz}}}}}$$ Hz around 15 kHz in ambient conditions. We then discuss the implications of this approach for the design of future magnetometers, including near-projection-limited devices approaching 3 fT/ $$\sqrt{{{{\rm{Hz}}}}}$$ Hz sensitivity enabled by spin refrigeration.

Abstract Background The development and egg-laying performance of hens are precisely regulated by hormones secreted by the pituitary. In this study, we performed comprehensive transcriptome sequencing of pituitary from Hy-Line Brown hens at 15, 20, 30 and 68 W of age. Through association analysis, we identified key genes and ceRNA regulatory networks related to pituitary development and egg production. Results Based on the comprehensive transcriptome data, we identified 470 differentially expressed lncRNAs (DE-lncRNAs), 38 differentially expressed miRNAs (DE-miRNAs), and 2,449 differentially expressed mRNAs (DE-mRNAs). Time-series analysis pinpointed genes and signaling pathways that significantly influence pituitary hormone secretion at various stages. At 15 W, the high expression of GHRHR, NPY1R, and TSHR in the pituitary supports growth. At 20 and 30 W, elevated GNRHR expression sustains continuous egg production. In the late laying period, the expression of PRL may lead to a decline in egg production. Additionally, association analysis enabled the construction of a ceRNA regulatory network involving non-coding RNAs that regulate the development and reproduction of hens. Conclusion This study elucidated the comprehensive transcriptome expression profiles of the pituitary gland during the development and egg-laying processes in Hy-Line Brown hens and constructed the associated molecular regulatory networks. These findings lay the foundation for investigating the mechanisms by which non-coding RNAs regulate pituitary hormone secretion.

Abstract Background: Exposure to high altitude increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Nomogram is a graphical regression model, but there are no reports on using nomogram to predict myocardial ischemia under high altitude exposure. Our goal was to establish prediction models based on pre-high-altitude physical exposure examination data and identify key risk factors. Methods: We prospectively enrolled a total of 2,855 healthy individuals who underwent physical examination at the 920th Hospital of Joint Logistics Support Force and were scheduled to undergo high-altitude (3000–3500 m) training within six months. These participants were randomly divided into a training cohort (75%) and a validation cohort (25%). In the training set, single-factor analysis of variance and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were used to select variables, and two nomograms were established based on clinical features (CF) and clinical features + blood tests (CF + BT), respectively. The performance of the nomograms was evaluated using the area under the receiver operating characteristic curve (ROC), the concordance index (C-index), and calibration curves. Results: The C-index for the prediction models CF and CF + BT were 0.652 and 0.804, respectively. In the training cohort, the AUC for prediction models CF and CF + BT were 0.61 and 0.80, respectively. In the validation cohort, the AUC for prediction models CF and CF + BT were 0.61 and 0.81, respectively. Conclusion: We have successfully established two nomogram models to predict myocardial ischemia under high-altitude exposure and identified some risk factors.

Abstract Background The associations between authoritarian personality and subjective well-being remains understudied, especially in China. In addition, as Chinese individuals and Chinese organizations generally attach importance to authority, exploring the matching effect of individual authoritarian personality and organizational culture (OC) can provide information for career selection, talent recruitment and university enrollment. The present study aimed to test associations between authoritarian personality traits (right-wing authoritarian, RWA; social dominance orientation, SDO) and subjective well-being (SWB; including positive affect, PA; negative affect, NA; and life satisfaction, LS) at the general and component-specific levels and the possible moderating role of OC (military or nonmilitary universities) on the associations in Chinese culture for the first time. Methods A total of 6,580 Chinese students from military and nonmilitary universities were surveyed using the Right Wing Authoritarianism Scale, Social Dominance Orientation Scale, Campbell Index of Well-being, Patient Health Questionnaire, and Satisfaction with Life Scale. Results A higher score on RWA, but lower on SDO, correlated with greater SWB at both the general level and the component-specific levels. The links of RWA/SDO and positive factors (PA/LS) of SWB as well as latent SWB were moderated by the OC (being in military or nonmilitary universities). Specifically, these correlations were stronger for military than for civilian students. Further, although the moderating roles of OC existed in all three subgroups (sex, age, and socioeconomic status [SES] level), the negative link between OC and latent SWB existed in the male, younger, and high-SES individuals, while this link was not significant in female, older, and low-SES ones. Conclusions The present study extends the findings of the moderating roles of organizational culture on the positive RWA–SWB relationship and the negative SDO–SWB relationship in oriental cultural contexts.

Abstract Background This study aims to investigate a novel instrument OM-100 with low-frequency magnetic fields (LFMFs) for its potential applicability in the treatment of liver cancer. Methods Liver cancer cell lines (HepG2 and Huh7) and normal liver cell line THLE-2 were exposed to OM-100 at LFMFs of 0, 10, 25, 50, and 100 kHz for 2 h in the morning, noon, and evening, respectively. The effects of LFMF on cell viability, apoptosis, migration, and invasion capabilities were examined. Additionally, impacts of LFMF on ROS production was assessed. In vivo studies were conducted to examine the safety profile of OM-100 and its effects on tumor growth. Results In vitro, OM-100 reduced the viability of liver cancer cells, increased cell apoptosis, and inhibited cell migration and invasion abilities in a frequency-dependent manner (P

Abstract Fibronectin type III domain-containing (FNDC) proteins play critical roles in cellular homeostasis and cardiac injury, and our recent findings define FNDC5 as a promising cardioprotectant against doxorubicin- and aging-related cardiac injury. FNDC4 displays a high homology with FNDC5; however, its role and mechanism in cardiac ischemia/reperfusion (I/R) injury remain elusive. Here, we show that cardiac and plasma FNDC4 levels are elevated during I/R injury in a hypoxia-inducible factor 1α (HIF1α)-dependent manner. Cardiac-specific FNDC4 overexpression facilitates, while cardiac-specific FNDC4 knockdown inhibits cardiomyocyte survival and angiogenesis in I/R-stressed hearts of male mice through regulating the proteasomal degradation of HIF1α. Interestingly, FNDC4 does not directly stimulate angiogenesis of endothelial cells, but increases the expression and secretion of fibroblast growth factor 1 from cardiomyocytes to enhance angiogenesis in a paracrine manner. Moreover, therapeutic administration of recombinant FNDC4 protein is sufficient to alleviate cardiac I/R injury in male mice, without resulting in significant side effects. In this work, we reveal that FNDC4 alleviates cardiac I/R injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis, and define FNDC4 as a promising predictive and therapeutic target of cardiac I/R injury.

Abstract Molecular dynamics (MD) is an indispensable atomistic-scale computational tool widely-used in various disciplines. In the past decades, nearly all ab initio MD and machine-learning MD have been based on the general-purpose central/graphics processing units (CPU/GPU), which are well-known to suffer from their intrinsic “memory wall” and “power wall” bottlenecks. Consequently, nowadays MD calculations with ab initio accuracy are extremely time-consuming and power-consuming, imposing serious restrictions on the MD simulation size and duration. To solve this problem, here we propose a special-purpose MD processing unit (MDPU), which could reduce MD time and power consumption by about 103 times (109 times) compared to state-of-the-art machine-learning MD (ab initio MD) based on CPU/GPU, while keeping ab initio accuracy. With significantly-enhanced performance, the proposed MDPU may pave a way for the accurate atomistic-scale analysis of large-size and/or long-duration problems which were impossible/impractical to compute before.

Abstract Background Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited. Methods Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies. Results All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases. Conclusions By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study. Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions: The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

This study examines the hot deformation behavior of Mo-14Re alloy at various true strains (15%, 35%, 65%) and strain rates (0.01 s−1, 10 s−1) at a temperature of 1400K. The findings indicate that dynamic recovery (DRV) and dynamic recrystallization (DRX) occur concomitantly as strain increases at a low strain rate of 0.01 s−1, with DRV being the predominant softening mechanism. At a strain of 65%, DRX emerges as the primary softening process. Conversely, under high strain rates of 10 s−1, DRX is inhibited, and the Mo-14Re alloy experiences work hardening due to an increase in dislocation density. Microscopic analysis shows that the high-density dislocations facilitate the continued nucleation and growth of recrystallized grains at low strain rates. At high strain rates, tangled dislocations hinder dislocation motion and recrystallization. Regarding texture evolution, stronger {100}//CD and weaker {111}//CD fiber texture is observed at low strain rates of 0.01 s−1, while stronger {111}//CD and weaker {100}//CD fiber texture forms at high strain rates of 10 s−1, with enhanced texture intensity. Mechanistic analysis confirms the activation of the {110}, {112}, and {123} dislocation slip systems at elevated temperatures, with the {123} system being the most dominant.

Equipment clusters are gradually emerging as a key way to improve the efficiency of underwater tasks. Traditional availability dependability capacity(ADC) models make it difficult to evaluate the collaborative ability of an underwater heterogeneous platform composed of multi-type equipment. The reliability, endurance, and communication performance indicators with time variables were selected, and a comprehensive model of the tree structure was established, which could quantify the collaborative factors numerically and objectively reflect the changes in collaborative ability during the platform task process. Based on this, the capability matrix was continuously processed, and the equipment individual was taken as a subsystem. Environmental impact factors were introduced to reflect the influence of the surrounding environment on the equipment performance. An improved ADC model was established for system effectiveness evaluation. By taking the underwater heterogeneous platform composed of autonomous undersea vehicles and communication nodes as an example, the equipment capability and platform effectiveness within the task cycle were evaluated. The research results indicate that this method can be well combined with multiple collaborative factors for effectiveness evaluation, which is feasible and effective and can provide a reference for the effectiveness evaluation of collaborative operation tasks of multi-type equipment.

Abstract Aim This study aims to investigate the current status of work engagement among ophthalmic specialized nurses in China and explore the multifaceted factors influencing work engagement from the physical, psychological, and social perspectives. Methods This study adopts a cross-sectional survey design, distributed electronic questionnaires through WeChat software, and 261 valid questionnaires were received from ophthalmic specialized nurses. The survey includes demographic information about ophthalmic specialized nurses, as well as work engagement, sleep quality and social support. A generalized linear model was used to investigate the factors influencing the work engagement of ophthalmic specialized nurses. Results The overall work engagement score among ophthalmic specialized nurses in our study was 143.70 ± 13.66. Multivariate analysis showed that participation in teaching, professional title, sleep quality and perceived social support were the influencing factors of work engagement of ophthalmic specialized nurses. Discussion The results showed that ophthalmic specialized nurses with the title of “senior nurse”, participating in teaching had higher work engagement. According to the Two-Factor Theory, incentive factors can stimulate the work enthusiasm of specialized nurses. The worse the sleep quality of ophthalmic specialized nurses, the lower the work engagement. It is suggested that nursing managers should pay attention to the sleep problems of specialized nurses and reduce work burnout. The nurses who perceived higher levels of social support exhibited higher work engagement. Because social support can mitigate nurses’ work burnout and work-related stress. Conclusion Ophthalmic specialized nurses in China demonstrate a relatively high level of work engagement. Those with the title of senior nurse, involvement in teaching, better sleep quality, and higher perceived social support exhibit higher work engagement.

Abstract Background In facial plastic surgery, patients with nasal deformity are often treated by rib cartilage transplantation. In recent years, cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material. In this study, we prepared an injectable nasal filler material containing poly‐L‐lactic acid (PLLA) porous microspheres (PMs), hyaluronic acid (HA) and adipose‐derived mesenchymal stem cells (ADMSCs). Methods We seeded ADMSCs into as‐prepared PLLA PMs using our newly invented centrifugation perfusion technique. Then, HA was mixed with ADMSC‐incorporated PLLA PMs to form a hydrophilic and injectable cell delivery system (ADMSC‐incorporated PMH). Results We evaluated the biocompatibility of PMH in vitro and in vivo. PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs. In vivo experiments, we observed that PMH has good biocompatibility and cartilage regeneration ability. Conclusion In this study, a injectable cell delivery system was successfully constructed. We believe that PMH has potential application in cartilage tissue engineering, especially in nasal cartilage regeneration.

Abstract Background Previous research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN). Methods A total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR–Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison. Results Among the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174–1.718, p

Abstract Background Anemone shikokiana (Makino) Makino is a perennial herb of the genus Anemone in the family Ranunculaceae. Endemic to the Shandong Peninsula in China and Shikoku Island in Japan, it is a rare and endangered plant with a narrow, disjunct distribution. It is threatened with extinction and is in urgent need of conservation. Evaluating the genetic diversity of species, revealing the population genetic structure and gene flow, and inferring the population history are of great importance for species conservation, especially for rare and endangered plants. Results In our study, 73 samples from eight wild populations in China were sequenced by Super-GBS, yielding a total of 40.59 G clean reads and 52,231 SNPs. Based on the obtained SNP data set, we evaluated the population genetic diversity, genetic structure, and gene flow of A. shikokiana. A low level of genetic diversity was found (He = 0.1925, Ho = 0.1422). The neighbor-joining (NJ) tree, principal component analysis and ADMIXTURE analysis suggested that these 73 A. shikokiana could be considered as two groups. Pairwise genetic differentiation coefficients (Fst) indicated that genetic differentiation was lower between adjacent populations and higher between geographically separated populations. The gene flow between Kunyu Mountain and Lao Mountain was very low. However, neither of the two regions showed evidence of Isolation by Distance. Conclusions Here, we revealed the population genetic structure and gene flow of A. shikokiana from the Shandong Peninsula, China. This research provides valuable genetic resources for A. shikokiana and contributes to the scientific and effective conservation of the species.

Abstract Cell motility increases the fitness of bacterial cells. Previous research focused on the transcriptional regulator CdsR, which represses cellular autolysis and promotes spore formation in Bacillus thuringiensis. However, the targets of CdsR are mostly unknown. Here, we reported a new function of CdsR in regulating cell motility. Mutation of cdsR results in increase of cell mobility, and a number of related genes were upregulated compared to wild type HD73. Thus, we investigated the transcription of the fla/che gene cluster, which involves in cell mobility and comprises eight operons/genes, including motAB1, cheY-yrhK, lamB-cheR, yaaR-fliG2, cheV-mogR, hag1, hag2, and yjbJ-flgG. Additionally, the motAB2 operon was discovered, which consists of homologs genes motA2 and motB2 that are like motA1 and motB1. Through promoter-lacZ fusion assays and EMSA experiments, it was discovered that CdsR directly regulates the motAB1, cheY-yrhK, lamB-cheR, yaaR-fliG2, cheV-mogR, hag1, hag2, yjbJ-flgG, and motAB2 operons by binding to their promoter regions. Importantly, it was confirmed that CdsR is a metalloregulator and the binding to promoter can be inhibited by Cu (II) ions. This research enhances our understanding of the regulation of cell mobility in B. thuringiensis.

The steel industry is considered an important basic sector of the national economy, and its high energy consumption and carbon emissions make it a major contributor to climate change, especially in China. The majority of crude steel in China is produced via the energy- and carbon-intensive blast furnace–basic oxygen furnace (BF–BOF) route, which greatly relies on coking coal. In recent years, China’s steel sector has made significant progress in energy conservation and emission reduction, driven by decarbonization policies and regulations. However, due to the huge output of crude steel, the steel sector still produces 15% of the total national CO2 emissions. The direct reduced iron (DRI) plus scrap–electric arc furnace (EAF) process is currently considered a good alternative to the conventional route as a means of reducing CO2 emissions and the steel industry’s reliance on iron ore and coking coal, since the gas-based DRI plus scrap–EAF route is expected to be more promising than the coal-based one. Unfortunately, almost no DRI is produced in China, seriously restricting the development of the EAF route. Here, we highlight the challenges and pathways of the future development of DRI, with a focus on China. In the short term, replacing natural gas with coke oven gas (COG) and byproduct gas from the integrated refining and chemical sector is a more economically feasible and cleaner way to develop a gas-based route in China. As the energy revolution proceeds, using fossil fuels in combination with carbon capture, utilization, and storage (CCUS) and hydrogen will be a good alternative due to the relatively low cost. In the long term, DRI is expected to be produced using 100% hydrogen from renewable energy. Both the development of deep processing technologies and the invention of a novel binder are required to prepare high-quality pellets for direct reduction (DR), and further research on the one-step gas-based process is necessary.

According to the complex differential accumulation history of deep marine oil and gas in superposition basins, the Lower Paleozoic petroleum system in Tahe Oilfield of Tarim Basin is selected as a typical case, and the process of hydrocarbon generation and expulsion, migration and accumulation, adjustment and transformation of deep oil and gas is restored by means of reservoine-forming dynamics simulation. The thermal evolution history of the Lower Cambrian source rocks in Tahe Oilfield reflects the obvious differences in hydrocarbon generation and expulsion process and intensity in different tectonic zones, which is the main reason controlling the differences in deep oil and gas phases. The complex transport system composed of strike-slip fault and unconformity, etc. controlled early migration and accumulation and late adjustment of deep oil and gas, while the Middle Cambrian gypsum-salt rock in inner carbonate platform prevented vertical migration and accumulation of deep oil and gas, resulting in an obvious “fault-controlled” feature of deep oil and gas, in which the low potential area superimposed by the NE-strike-slip fault zone and deep oil and gas migration was conducive to accumulation, and it is mainly beaded along the strike-slip fault zone in the northeast direction. The dynamic simulation of reservoir formation reveals that the spatio-temporal configuration of “source-fault-fracture-gypsum-preservation” controls the differential accumulation of deep oil and gas in Tahe Oilfield. The Ordovician has experienced the accumulation history of multiple periods of charging, vertical migration and accumulation, and lateral adjustment and transformation, and deep oil and gas have always been in the dynamic equilibrium of migration, accumulation and escape. The statistics of residual oil and gas show that the deep stratum of Tahe Oilfield still has exploration and development potential in the Ordovician Yingshan Formation and Penglaiba Formation, and the Middle and Upper Cambrian ultra-deep stratum has a certain oil and gas resource prospect. This study provides a reference for the dynamic quantitative evaluation of deep oil and gas in the Tarim Basin, and also provides a reference for the study of reservoir formation and evolution in carbonate reservoir of paleo-craton basin.

Abstract The high non-radiative energy loss is a bottleneck issue that impedes the improvement of organic solar cells. The formation of triplet exciton is thought to be the main source of the large non-radiative energy loss. Decreasing the rate of back charge transfer is considered as an effective approach to alleviate the relaxation of the charge-transfer state and the triplet exciton generation. Herein, we develops an efficient ternary system based on D18:N3-BO:F-BTA3 by regulating the charge-transfer state disorder and the rate of back charge transfer of the blend. With the addition of F-BTA3, a well-defined morphology with a more condensed molecular packing is obtained. Moreover, a reduced charge-transfer state disorder is demonstrated in the ternary blend, which decreases the rate of back charge transfer as well as the triplet exciton formation, and therefore hinders the non-radiative recombination pathways. Consequently, D18:N3-BO:F-BTA3-based device produces a low non-radiative energy loss of 0.183 eV and a record-high efficiency of 20.25%. This work not only points towards the significant role of the charge-transfer state disorder on the suppression of triplet exciton formation and the non-radiative energy loss, but also provides a valuable insight for enhancing the performance of OSCs.

Abstract Leaf Area Index (LAI) is a critical parameter in terrestrial ecosystems, with high spatial resolution data being extensively utilized in various research studies. However, LAI data under future scenarios are typically only available at 1° or coarser spatial resolutions. In this study, we generated a dataset of 0.05° LAI (F0.05D-LAI) from 1983–2100 in a high spatial resolution using the LAI Downscaling Network (LAIDN) model driven by inputs including air temperature, relative humidity, precipitation, and topography data. The dataset spans the historical period (1983–2014) and future scenarios (2015–2100, including SSP-126, SSP-245, SSP-370, and SSP-585) with a monthly interval. It achieves high accuracy (R² = 0.887, RMSE = 0.340) and captures fine spatial details across various climate zones and terrain types, indicating a slightly greening trend under future scenarios. F0.05D-LAI is the first high-resolution LAI dataset and reveals the potential vegetation variation under future scenarios in China, which benefits vegetation studies and model development in earth and environmental sciences across present and future periods.

Abstract Background Mutation of MMACHC gene causes cobalamin C disease (cblC), an inherited metabolic disorder, which presents as combined methylmalonic aciduria (MMA-uria) and hyperhomocysteinaemia in clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported. This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists. Case presentation Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical presentation. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealing elevated serum and urine homocysteine, renal biopsy showing TMA and tubular injury, along with genetic testing showing heterogeneous compound mutations in MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them got improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered. Conclusions The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease. Clinical Trial Number Not applicable.

Abstract Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Abstract Background Bilateral duplicated kidney and ureter is a rare condition in urology, and it is even rarer for patients to have multiple stones simultaneously. We delineate the diagnostic and therapeutic trajectory of a patient presenting with bilateral duplex kidneys and ureters, characterized by the presence of multiple stones. Notably, the left kidney is a complete duplication, whereas the right kidney exhibits an incomplete duplication. Case presentation A 47-year-old male patient was diagnosed with bilateral duplex kidney and ureter combined with multiple stones. Ureteral flexible lithotripsy and percutaneous nephrolithotomy were performed successively in our hospital. On the postoperative five day, he was discharged from the hospital without apparent discomfort.The double J tube was pulled out one month later, and no stone recurrence was found after 3 months of follow-up. Conclusions Bilateral duplicated renal ureteral malformations combined with multiple stones are very rare. Stones can be removed by ureteroscopic lithotripsy or percutaneous nephrolithotripsy and sometimes multiple procedures are required, which should be chosen according to the patient’s relevant condition.

Abstract Objective To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2‐related epilepsy. Methods A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next‐generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations. Results We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5–S6 segments and the C‐terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video‐electro‐encephalography, three cases with self‐limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2‐DEE. At the final follow‐up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2‐DEE had mild to severe developmental backwardness. Significance Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2‐related epilepsy. The gene mutation sites are mostly located in S5–S6 segments and the C‐terminal region, and the former is usually associated with KCNQ2‐DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2‐DEE. Some cases with KCNQ2‐related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2‐DEE. Plain Language Summary This article reports 23 cases of children with KCNQ2‐related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2‐related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2‐related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.

Abstract Understanding how landscape structure and riparian vegetation impact bee diversity is important for maintaining pollination service in urban areas. We explored spatial and temporal variation of bee communities across land use types in a riparian zone of a mountainous megacity in 2018 and 2022, examined whether riparian vegetation functions as corridors that maintain gene flow of bee populations, and mapped pollination supply at the landscape scale. Pielou index was higher in 2018 than in 2022, while no significant differences in abundance, Shannon and richness index were observed. The abundance of bees and the Shannon index were significantly and positively correlated with the abundance of flowers on grassland and forested land, respectively, while both were negatively correlated with the area of the building. The genetic differentiation of the bee communities in the riparian zone was lower than those outside, indicating the function of the riparian vegetation corridor. The pollination supply varied significantly between regions, with medium to high degree of pollination supply distributed primarily in residual habitats and the surrounding urban green spaces, while low degree in the remaining areas. Our results stress the importance of maintaining the continuity of vegetation in riparian zones and increasing flower abundance, especially native plant species, for the conservation of bees in urban areas. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Exacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes. Methods We included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed. Results This extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources. Conclusions The results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients.

Abstract Background Loneliness is a risk factor for numerous negative life outcomes and diseases among older adults. Physical exercise can reduce social isolation among older adults and improve their health status. This study focused on the relationships among physical exercise, perceived social support, resilience and loneliness to provide theoretical support for physical exercise interventions to address loneliness in older adults. Methods This study used a structural equation model and bootstrap method to test a serial mediation model of physical exercise and loneliness and the role of perceived social support and resilience. In this descriptive and cross-sectional study, a questionnaire survey was conducted on 516 older adults from 5 January 2024 to 20 January 2024. The data were collected using the physical activity rating scale (PARS-3), UCLA loneliness Scale-8 (ULS-8), perceived social support scale (PSSS) and Connor-Davidson Resilience Scale (CD-RISC). Results The results showed that physical exercise among older adults had a direct negative relationship with loneliness (Effect = -0.049, 95% CI: -0.072 to -0.027). In addition, perceived social support and resilience mediated the relationship between physical exercise and loneliness both independent and serially, with the independent mediation effect of perceived social support being − 0.041 (95% CI: -0.056 to -0.028), the independent mediation effect of resilience being − 0.018 (95% CI: -0.026 to -0.011), and the serial mediation effect of perceived social support and resilience being − 0.009 (95% CI: -0.015 to -0.005). The total indirect effect of the three mediation paths was 58.47%. Conclusions (1) In this study, physical exercise and loneliness in older adults were negatively correlated. Perceived social support and resilience play mediating roles in the relationship between physical exercise and loneliness. (2) This study suggests that participation in group events or team sports is valuable for alleviating loneliness caused by a lack of social interaction.

Abstract Background N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional mechanism, plays a pivotal role in RNA modification and tumor progression. However, the molecular mechanism by which ac4C modification mediates tumor immunosuppression remains elusive in triple-negative breast cancer (TNBC). Methods NAT10 expression was analyzed in TNBC samples in the level of mRNA and protein, and compared with the corresponding normal tissues. ac4C modification levels also measured in the TNBC samples. The effects of NAT10 on immune microenvironment and tumor metabolism were investigated. NAT10-mediated ac4C and its downstream regulatory mechanisms were determined in vitro and in vivo. The combination therapy of targeting NAT10 in TNBC was further explored. Results The results revealed that the loss of NAT10 inhibited TNBC development and promoted T cell activation. Mechanistically, NAT10 upregulated JunB expression by increasing ac4C modification levels on its mRNA. Moreover, JunB further up-regulated LDHA expression and facilitated glycolysis. By deeply digging, remodelin, a NAT10 inhibitor, elevated the surface expression of CTLA-4 on T cells. The combination of remodelin and CTLA-4 mAb can further activate T cells and inhibite tumor progression. Conclusion Taken together, our study demonstrated that the NAT10-ac4C-JunB-LDHA pathway increases glycolysis levels and creates an immunosuppressive tumor microenvironment (TME). Consequently, targeting this pathway may assist in the identification of novel therapeutic strategies to improve the efficacy of cancer immunotherapy.

Abstract The world is facing a global nutrition crisis, as evidenced by the rising incidence of metabolic disorders such as obesity, insulin resistance and chronic inflammation. Skeletal muscle is the largest tissue in humans and plays an important role in movement and host metabolism. Muscle fibre formation occurs mainly during the embryonic stage. Therefore, maternal lifestyle, especially nutrition and exercise during pregnancy, has a critical influence on foetal skeletal muscle development and the subsequent metabolic health of the offspring. In this review, the influence of maternal obesity, malnutrition and micronutrient intake on foetal skeletal muscle development is systematically summarized. We also aim to describe how maternal exercise shapes foetal muscle development and metabolic health in the offspring. The role of maternal gut microbiota and its metabolites on foetal muscle development is further discussed, although this field is still in its ‘infancy’. This review will provide new insights to reduce the global crisis of metabolic disorders and highlight current gaps to promote further research.

Despite significant advances in targeted therapies and immunotherapies, non-small cell lung cancer (NSCLC) continues to present a global health challenge, with a modest five-year survival rate of 28 %, largely due to the emergence of treatment-resistant and metastatic tumors. In response, we synthesized a novel bioactive compound, ethyl 6-chlorocoumarin-3-carboxylyl L-theanine (TClC), which significantly inhibited NSCLC growth, epithelial mesenchymal transition (EMT), migration, and invasion in vitro and tumor growth and metastasis in vivo without inducing toxicity. TClC disrupts autocrine loops that promote tumor progression, particularly in stem-like CD133-positive NSCLC (CD133+ LC) cells, which are pivotal in tumor metastasis. Through targeted molecular assays, we identified direct binding targets of TClC, including Akt, NF-κB, β-catenin, EZH2, and PD-L1. This interaction not only suppresses the expression of oncogenic factors and cancer stem cell markers but also downregulates the expression of a multidrug resistance transporter, underscoring the compound's polypharmacological potential. These results position TClC as a promising candidate for NSCLC treatment, signaling a new era in the development of cancer therapies that directly target multiple critical cancer pathways.

The T4 heat treatment process is essential for hot-press sintered aluminum matrix composites. This study investigates the evolution mechanism of novel T4 (TiC + B4C)/6061Al composites by combining vacuum hot-press sintering with various T4 heat treatments. Results show that due to the addition of B4C, in-situ SiC and diffusion of B appeared in T4 (TiC + B4C)/6061Al composites. Severe grain boundary segregation of Mg occurred in T4 6061Al, while grain boundary segregation of Mg is noticeably reduced in T4 (TiC + B4C)/6061Al composites. Unlike the ductile fracture and intergranular fracture observed in T4 6061Al, fracture in T4 (TiC + B4C)/6061Al composites predominantly occurs through ductile fracture of the aluminum matrix and cleavage fracture of particles. During T4 heat treatment, the addition of TiC and B4C not only refined the grain size of 6061Al but also promoted the occurrence of static recrystallization of 6061Al. With the increase of solution temperature, the recrystallization volume fraction of the aluminum matrix in T4 (TiC + B4C)/6061Al composites first increased and then decreased slightly, the hardness and strength of T4 (TiC + B4C)/6061Al composites increased gradually, the plasticity first increased and then decreased. An optimal balance between strength and plasticity in T4 (TiC + B4C)/6061Al composites can be achieved at the solution temperature of 530 °C.

Change detection has become a crucial topic in the field of remote sensing deep learning due to its extensive application in earth observation. However, real remote sensing images often contain multiple land cover classes with significant intraclass variability and interclass similarity, limiting the performance of change detection in complex scenarios. To address this, we leverage the capabilities of vision foundation models by applying the segment anything model (SAM) to remote sensing change detection, and we name this method dual encoder–decoder SAM (DED-SAM). Specifically, we construct a DED framework, utilizing a small-scale change detection model in both branches to generate mixed prompts including image features, mask prompts, and box prompts. The SAM 2 model is used for fine-grained recognition of dual-temporal images, generating accurate, and stable feature boundaries, which are then used as constraints to generate the final change mask. To validate the effectiveness of DED-SAM across various application scenarios, we conduct quantitative experiments on three public datasets: Levir-CD, SYSU-CD, and CDD, testing its detection capabilities under single change categories, multiple change categories, and seasonal pseudochange interference. The results show that the proposed DED-SAM achieved state-of-the-art F1 scores and IoUs on these three datasets: LEVIR-CD (92.00%, 85.11%), SYSU-CD (84.15%, 72.01%), and CDD (97.72%, 95.47%).

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

Galvanic corrosion behavior of AZ91D alloy / 45 steel couple in 3.5 wt.% NaCl solution under 0, 0.2 and 0.4 T magnetic field were studied by microstructure observation, immersion test and electrochemical measurement. The mixed potential theory was used to estimate the galvanic current density and the mixed potential of the galvanic corrosion between AZ91D alloy and 45 steel. The results indicated that magnetic field could accelerate the corrosion of AZ91D alloy, and impede the corrosion process of 45 steel. The effect of magnetic field on corrosion sensibility and corrosion rate of these two alloys increased as the intensity rising. The galvanic corrosion rate of the couple was accelerated by magnetic field. With the magnetic field intensity rising, the galvanic corrosion sensibility and corrosion rate of the couple increased. The effects of magnetic field on the galvanic corrosion performance of the couple and the corrosion behavior of AZ91D alloy and 45 steel were due to the appearance of field gradient force and magnetohydrodynamic (MHD) force. The mixed potential theory has a certain accuracy to estimate the Ecouple and icouple values in this work.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Abstract Deep learning-based MRI reconstruction models have achieved superior performance these days. Most recently, diffusion models have shown remarkable performance in image generation, in-painting, super-resolution, image editing and more. As a generalized diffusion model, cold diffusion further broadens the scope and considers models built around arbitrary image transformations such as blurring, down-sampling, etc. In this paper, we propose a k-space cold diffusion model that performs image degradation and restoration in k-space without the need for Gaussian noise. We provide comparisons with multiple deep learning-based MRI reconstruction models and perform tests on a well-known large open-source MRI dataset. Our results show that this novel way of performing degradation can generate high-quality reconstruction images for accelerated MRI.