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Abstract The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBDXBB.1.5-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBDXBB.1.5-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBDXBB.1.5-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (TRM) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBDXBB.1.5-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBDXBB.1.5-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBDXBB.1.5-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBDXBB.1.5-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

Abstract Fluorouracil-based chemotherapy responses in colorectal cancer (CRC) patients vary widely, highlighting the role of pharmacogenomics in developing better predictive models. We analyzed 379 CRC patients receiving fluorouracil-based chemotherapy, collecting data on fluorouracil metabolism-related SNPs (TYMS, MTHFR, DPYD, RRM1), blood inflammatory markers, and clinical status. Six machine learning models—K-nearest neighbors, support vector machine, gradient boosting decision trees (GBDT), eXtreme Gradient Boosting (XGBoost), LightGBM, and random forest—were compared against multivariate logistic regression and a deep learning model (i.e., multilayer perceptron, MLP). Feature importance analysis highlighted seven predictors: histological grade, N and M staging, monocyte count, platelet-to-lymphocyte ratio, MTHFR rs1801131, and RRM1 rs11030918. In a five-fold cross-validation, XGBoost and GBDT exhibited superior performance, with Area Under Curve (AUC) of 0.88 ± 0.02. XGBoost excelled in identifying favorable prognosis (recall = 0.939). GBDT demonstrated balance in recognizing both categories, with a recall for favorable prognosis of 0.908 and a precision for unfavorable prognosis of 0.863. MLP had a similar AUC (0.87) with high precision for favorable prognosis (recall = 0.946). In external validation, XGBoost model achieved an accuracy of 0.79. An online prognostic tool based on XGBoost was developed, integrating metabolism-related SNPs and inflammatory markers, enhancing CRC treatment precision and supporting tailored chemotherapy.

Abstract The dynamic crack propagation trajectories play a crucial role in enhancing our understanding of spatial mechanisms involved in crack expansion. However, visualization of internal cracks under complex crack conditions has always been a challenge. Biological networks have been honed by many cycles of evolutionary selection pressure and are likely to yield reasonable solutions to such combinatorial optimization problems. This study applied the slime mould algorithm to improve the accuracy of internal crack localization in rocks and employed Minimum spanning tree and Gaussian mixture model to construct the crack propagation trajectories. By introducing the concept of bond length, the evolution characteristics of crack levels were effectively characterized. Research results showed that this approach effectively preserves essential crack localization information while mitigating the influence of interfering parameters, providing crack characterization results that exhibit high consistency with actual fracture patterns. The curves of cumulative bond length and relative bond length over time conform to the trend of a Growth/Sigmoidal curve. The strength of the bond was correlated with the temporal process of crack propagation. This result could be helpful for analyzing crack trajectories and predicting rock stability.

Abstract We investigated the Strong Cosmic Censorship (SCC) conjecture in Einstein–Power–Maxwell–de Sitter (EPMdS) black holes by analyzing the quasinormal modes (QNMs) of a massless neutral scalar field perturbation. Using the pseudospectral method, we calculated the QNM frequencies across various cosmological constants and nonlinear electromagnetic parameters. Our results show that for black holes far from extremality, the lowest QNM frequency $$-\text {Im} (\omega )/\kappa _-$$ - Im ( ω ) / κ - remains below 1/2. However, as the black holes approach extremality, the lowest mode’s $$-\text {Im} (\omega )/\kappa _-$$ - Im ( ω ) / κ - consistently exceeds 1/2, leading to a violation of SCC. Moreover, with a fixed cosmological constant, as the nonlinearity parameter $$\alpha $$ α increases, the interval of SCC violation under the charge extremality ratio narrows. Considering that $$k = 1/2 + 1/\alpha $$ k = 1 / 2 + 1 / α is inversely proportional to $$\alpha $$ α , our results indicate that increasing the order k of the non-linear electromagnetic field can effectively mitigate SCC violations.

Introduction: Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. Objectives: We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. Methods: Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. Results: SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. Conclusions: CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR.

Use of nanomaterials (NMs) to improve plant abiotic stress tolerance (AST) is a hot topic in NM-enabled agriculture. Previous studies mainly focused on the physiological and biochemical responses of plants treated with NMs under abiotic stress. To use NMs for improving plant AST, it is necessary to understand how they act on this tolerance at the omics and epigenetics levels. In this review, we summarized the knowledge of NM-improved abiotic stress tolerance in relation to omics (such as metabolic, transcriptomic, proteomic, and microRNA), DNA methylation, and histone modifications. Overall, NMs can improve plant abiotic stress tolerance through the modulation at omics and epigenetics levels.

Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Pseudorabies virus (PRV) can establish lifelong latent infection in peripheral nervous ganglion, and persistent infections in peripheral blood lymphocytes. Establishing an infection in the lymphocytes does not only enable the PRV to escape host immune surveillance but pass through the placental barrier, leading to fetal death and abortion. Due to the pathogenicity of the PRV, it poses a huge challenge in its prevention and control. The PRV escapes host immunity through downregulation of swine leukocyte antigen class I (SLA I) molecules on infected cells. However, data on the molecular mechanisms of the SLA I suppression remains scant. Here, in order to verify the effect of candidate proteins PRV pUL44 and pUS6 on PRV immune escape related molecules SLA I and peptide loading complex (PLC), we detected the expression of SLA I and PLC components after expressing PRV pUL44 and pUS6. The effects of pUS6 and pUL44 on SLA I and PLC were analyzed by qRT-PCR and Western blot at mRNA and protein level, respectively. Cells expressing pUS6 or pUL44 genes showed a significantly suppressed expression of surface and total SLA I molecules. In addition, unlike UL44, the US6 gene was shown to downregulate the transporter associated with antigen processing 1 (TAP1), TAP2 and Tapasin molecules. The results show that PRV pUS6 may participate in virus immune escape by directly regulating the SLA I, TAP dimer and Tapasin molecules, thus blocking the transportation of TAP-bound peptides to the ER to bind SLA I molecules. We provide a theoretical basis on the mechanism of TAP mediated immune escape by the PRV.

Abstract Background In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial. Results Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process. Conclusions Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

Chlorophorus fainanensis Pic, 1918 is redescribed. Four species, C. coniperda Holzschuh, 1992, C. diversicolor Holzschuh, 2016, C. orbatus Holzschuh, 1991 and C. pinguis Holzschuh, 1992 are newly reported from China. A new synonymy, Chlorophorus arciferus (Chevrolat, 1863) = Chlorophorus semisinuatus Pic, 1949, syn. nov. is proposed.

A novel Qingke Baijiu was produced by the process of light-aroma Baijiu combined with high-temperature stacking process and using highland barley of Tibet as material. Three kinds of Qingke Baijiu samples were evaluated by quantitative descriptive analysis, and analyzed by liquid-liquid extraction combined with gas chromatography-mass spectrometry and gas chromatography-olfactometry-mass spectrometry and analyzed by partial least squares regression analysis to clarify the aroma characteristic of the novel Qingke Baijiu and to investigate the influence of different manufacturing process. A total of 139 volatile compounds and 57 aroma compounds were detected in three samples, which included 11 aroma active compounds with odor active value (OAV) greater than 1. The total concentration of volatile compounds was 1.4 times higher after secondary fermentation. The sorghum and Zao aromas increased in the samples after secondary fermentation, where ethyl caprylate, ethyl caproate, ethyl isovalerate, and guaiacol were the corresponding key differential compounds. The sorghum and Zao aromas decreased after high-temperature stacking process, while floral aroma increased. Compared with the samples without high-temperature stacking process, the OAV of isoamyl acetate, guaiacol and 4-methylguaiacol increased, while the OAV of ethyl butyrate, ethyl caproate, and ethyl caprylate declined. After high-temperature stacking process, the concentration of isoamyl acetate increased, which lead to stronger floral aroma, and the concentration of butyric acid, ethyl caproate, ethyl caprylate, and ethyl decanoate declined, which lead to weaker sorghum aroma.

The primary cause of the decrease in thermal conductivity of conventional thermal conductive magnesium alloys is electron scattering brought on by solute atoms. However, the impact of phase interface on thermal conductivity of magnesium alloys is usually disregarded. This study has developed a Mg-Si-Zn-Cu alloy with high thermal conductivity that is distinguished by having a very low solute atom content and a significant number of phase interfaces. The thermal conductivity of the Mg-1.38Si-0.5Zn-0.5Cu alloy raises from its untreated value of 133.2 W/(m·K) to 142.2 W/(m·K), which is 91% of the thermal conductivity of pure Mg. This is accomplished by subjecting the alloy to both 0.8wt% Ce modification and T6 heat treatment. The morphology of eutectic Mg2Si phase is changed by Ce modification and heat treatment, and as a result, the scattering of electrons at the Mg2Si/Mg interface is reduced, resulting in increase of the alloy's thermal conductivity.

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Abstract RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions.

Abstract Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

Traditional Chinese villages, as rural settlements shaped over extensive historical evolution in agrarian societies, have lacked a systematic method for quantitatively analysing and understanding the historical spatial forms. This study takes a morphological research perspective, using Lohong Village, Su’er Village, and Shangyue Village in Guangdong Province as case studies of typical Cantonese traditional villages. It focuses on three key spatial texture elements: roads, plots, and architecture, employing parametric modelling techniques to investigate their combination patterns and quantitative characteristics. The findings indicate that: (1) Parametric analysis techniques can comprehensively, quantitatively, and accurately reveal the patterns of village spatial texture; (2) Comparing optimized parametric simulation results with original villages shows high similarity in spatial texture, demonstrating the method’s high fidelity and practical value; (3) The study explores a research approach suitable for the computer era – “data collection – parametric feature extraction and optimization – simulation and data calibration” – to study the spatial texture of traditional villages. Furthermore, it establishes a parametric-based platform for rural planning and construction management, providing a digital design pathway and management basis to preserve and inherit the historical village aesthetics.

Abstract This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.

Abstract Background The incidence of chronic diseases is on the rise worldwide, with a high mortality rate in China, posing a serious threat to the health-related quality of life (HRQoL) of middle-aged and older adults. This study explores the association between chronic diseases and the HRQoL of middle-aged and older adults, as well as the role of physical activity (PA) and degree of digitization in this relationship. Methods The data used in this study was obtained from the 2018 China Health and Retirement Longitudinal Study (CHARLS), which included 13,620 middle-aged and older Chinese adults (≥ 45 years). The study utilized correlation analysis, and bootstrapping to investigate the mediating role of PA and the moderating influence of the degree of digitization. Data analysis was conducted using SPSS 26.0. Results The study findings indicate that the severity of chronic disease has a significant negative predictive effect on HRQoL (PCS, physical component summary; MCS, mental component summary) (PCS: β = -2.515, p

Abstract So far, a variety of metabolite components of kiwifruit have been elucidated. However, the identification and analysis of flavonoids in different tissues of kiwifruit are rarely carried out. In this study, we performed transcriptome and metabolome analyses of roots (Gkf_R), stems (Gkf_T), leaves (Gkf_L), and fruits (Gkf_F) to provide insights into the differential accumulation and regulation mechanisms of flavonoids in kiwifruit. Results showed that a total of 301 flavonoids were identified, in four tissues with different accumulation trends, and a large proportion of flavonoids had high accumulation in Gkf_L and Gkf_R. A total of 84 genes have been identified involved in the flavonoid biosynthesis pathway, and the expression levels of five LAR, two DFR, and one HCT were significantly correlated with the accumulation of 16 flavonoids and co-localized in the flavonoid biosynthesis pathway. In addition, a total of 2362 transcription factor genes were identified, mainly MYBs, bHLHs, ERFs, bZIPs and WRKYs, among which the expression level of bHLH74, RAP2.3L/4L/10L, MYB1R1, and WRKY33 were significantly correlated with 25, 56, 43, and 24 kinds of flavonoids. Our research will enrich the metabolomic data and provide useful information for the directed genetic improvement and application in the pharmaceutical industry of kiwifruit.

Abstract Background Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates. Methods A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals. Results The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO. Conclusion Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

Abstract Optical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.

Abstract Emerging evidence highlights cellular senescence’s pivotal role in chronic kidney disease (CKD). Proximal tubule epithelial cells (PTECs) and fibroblasts are major players in CKD and serve as cellular sources of senescence. The generation of a conditionally immortalized human kidney cell model would allow to better understand the specific mechanisms and factors associated with cellular senescence in a controlled setting, devoid of potential confounding factors such as age and comorbidities. In addition, the availability of human kidney cell lines for preclinical research is sparse and most cell lines do not reflect their in vivo counterparts due to their altered behavior as immortalized cancer-like cells. In this study, PTECs and fibroblasts from human kidneys were isolated and transduced with doxycycline-inducible simian virus 40 large T antigen (SV40LT) vector. By comparing their gene expression with single-cell RNA sequencing data from human kidneys, the newly produced human kidney cell lines demonstrated significant resemblances to their in vivo counterparts. As predicted, PTECs showed functional activity and fibroblasts responded to injury with fibrosis. Withdrawal of the immortalizing factor doxycycline led to p21+ cell-cycle arrest and the key hallmarks of senescence. The obtained senescence gene set largely overlapped between both cell lines and with the previously published SenMayo set of senescence-associated genes. Furthermore, crosstalk experiments showed that senescent PTECs can cause a profibrotic response in fibroblasts by paracrine actions. In 76 human kidney sections, the number of p21+ cells correlated with the degree of fibrosis, age and reduced glomerular filtration, validating the role of senescence in CKD. In conclusion, we provide a novel cellular ex vivo model to study kidney senescence which can serve as a platform for large scale compounds testing.

Abstract Background Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. Case presentation This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. Conclusions These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Abstract Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

ObjectiveTo evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer. MethodsSubjects were selected from a population attending the Inner Mongolia Medical University Hospital. Each subject underwent a combined multi-target fecal FIT-DNA test (experimental group), a serum tumor marker test and enteroscopy (control group). The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals. ResultsThe data of 115 individuals were analyzed. Serum tumor markers test had a sensitivity of 63.2% (43/68) and a specificity of 74.5% (35/47). The enteroscopy had a sensitivity of 97.1% (66/68) and a specificity of 80.7% (38/47); the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7% (61/68) and a specificity of 87.2% (41/47). ConclusionThe sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection. Although its sensitivity is lower than enteroscopy, its operation is simpler and can be tested at home.

Plantago major (Plantaginaceae) is a medicinal plant in Chinese folk culture, known for its famous medicinal components such as plantagomain. In this study, we conducted genome sequencing of P. major using Illumina sequencing technology. The assembled complete chloroplast genome had a length of 165,044 bp, comprising a large single-copy regions (82,963 bp), a small single-copy regions (4,633 bp), and a pair of inverted repeat regions (38,724 bp). A total of 140 genes were detected, including 94 CDS, 38 tRNA, and 8 rRNA. Phylogenetic analysis revealed a close genetic relationship between P. major and P. rigida. These findings provide valuable data for a comprehensive understanding of the biological characteristics of P. major.

To explore the quality evaluation indicators of walnut and pecan varieties cultured in Yunnan, the contents of 12 nutritional indicators which included in mineral elements, protein, crude fat, and vitamin C of 27 walnut varieties were determined. 12 indicators were comprehensively explored by correlation analysis, principal component analysis and cluster analysis to reveal variation and comprehensive quality of walnut resources in Yunnan Province. Results showed that the variation of the content of 12 indicators was relatively rich, the variation coefficient ranged from 5% to 83%, among which the variation coefficient of vitamin C was the largest and the variation coefficient of crude fat was the smallest. The order of the average contents of 9 mineral elements was K>P>Mg>Ca>Mn>Na>Fe>Zn>Cu. The average contents of protein, fat and vitamin C were 15.62%, 68.63% and 4.66 mg/100 g, respectively. As demonstrated by the results of correlation analysis on 12 indicators, there was a significant positive correlation between protein and P, Fe, Mg, Ca, and Cu. The principal component analysis was used to comprehensively evaluate, showed that the comprehensive quality of walnut varieties 'Xiangcha' 'Yongping' 'Wanshu' and 'Xiaoyuanguo' were the best and the pecan variety 'Kaduo' was the better. The clustering analysis results showed that it can be divided into two major categories, namely the group rich in mineral elements and the group with high fat content. Subsequently, by combining with cluster analysis, K, Fe, Mg, Ca, Cu, protein and fat were determined as the critical indicators to evaluate the quality of walnut and pecan varieties cultured in Yunnan. Pecan varieties were suitable for extracting oil, and 22 main walnut varieties were suitable for direct consumption or the development of functional beverages rich in mineral elements and protein. The study clarified the critical indicators for evaluating the quality of Yunnan walnut and explored its quality characteristics, providing a scientific classification method, and laying a theoretical basis for the construction of the Yunnan walnut quality evaluation system.

Abstract Objective The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. Methods A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5–10 days after the first evaluation. Results The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p 0.05). The Cronbach’s α of the CNS-BFSC was 0.972. Conclusion The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018–1/2019 and 12/2021–1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P

【Objective】 Non-pressurized mesh filters are often installed in front of pumps to filter sediments and debris. In this paper, we study the influence of different irrigation water sources and backwash device parameters on hydraulic performance of a new network filter. 【Method】 The water flow rate in the experiment ranged from 120 to 160 m3/h, and the sediment concentration in the water varied from 0.2 to 0.8 g/L. The backwash varied from 1 to 20 m3/h, and the velocity gradient in the filter box changed from 1 to 4 r/min. A multi factor dispersion analysis method was used to analyze the experimental results. 【Result】 ① The initial sediment concentration had minimal impact on hydraulic performance of the mesh filter, contributing only 0.010 8 to the overall effect. However, the influence of water flow duration on the initial sediment concentration was significant, exceeding 159%. ② The fourth model provided the best fit for the overall regression analysis, with a residual value of 0.804 4, significantly higher than other models; its coefficient of determination R2 was 0.986 1. ③ the optimal performance was achieved when flow rate was 120.198 m3/h, velocity was 1.112 r/min, and self-cleaning flow rate was 19.934 m3/h. The associated a minimum energy loss was 16.024 kPa. 【Conclusion】 The model we proposed can accurately predict the impact of operation conditions and sediment concentration in the water on the performance of the non-pressurized mesh filters. Selecting optimal operation conditions can minimize the energy loss across the filter.

Abstract Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

Abstract Background Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR). Methods To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran’s Q-test and the MR Egger intercept test. Results The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209–2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044–1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062–2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039–1.425, P = 0.015). Conclusions Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.

As a benzoylurea insecticide, diflubenzuron (DFB) has been widely used in the prevention and control of diseases and insect pests in vegetables, fruits, grain cultivation, and other fields in recent years. In addition, because of its low acute toxicity, excellent biological activity, and specific action mechanism, DFB has been widely used in aquaculture to kill bacteria and lice. With its large-scale production and widespread use, its partial residue remains in environmental media, such as water, soil, and the atmosphere, and causes direct or indirect chronic toxicity to aquatic organisms. The residual DFB enters the human body along the food chain and poses a threat to human health when it reaches a certain concentration through chronic exposure and long-term accumulation. At present, research on DFB insecticides has been limited to the usage and dosage, residual metabolism, and its toxicological effects on the environment. There have been no reports, to our knowledge, on the effect of DFB on gene expression in carp liver in China. The purpose of this study was to explore the differential expression of genes in carp liver under DFB stress.In this study, carp (Cyprinus carpio) was selected as the research subject, and three exposure experiments for 15 days under 0.1 and 1.0 mg/L medicated bath concentrations were carried out in parallel for each concentration. High-throughput sequencing of the liver was performed using the Illumina NovaSeq 6000. Differentially expressed genes (DEGs) were screened by Padj < 0.05 and |log2FoldChange| ≥1, and bioinformatics analysis, such as Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, were performed. The transcriptome analysis results showed that 2 406 and 2 688 DEGs changed significantly at 0.1 and 1.0 mg/L exposure concentrations, respectively, and 821 DEGs were co-expressed between the two groups. GO analysis results showed that DEGs in the DFB exposure group were enriched in biological processes, cell compositions, and molecular functions. KEGG enrichment analysis showed that DEGs in the low DFB concentration exposure group were significantly enriched in metabolic pathways, such as biodegradation and metabolism of xenobiotics, lipid metabolism, carbohydrate metabolism, amino acid metabolism, signal molecules and interactions, endocrine system, and immune system. In addition to the above metabolic pathways, DEGs in the high DFB concentration exposure group were significantly enriched in metabolic pathways, such as folding, classification and degradation, transport, and catabolism.Studies have shown that DFB exposure causes the biodegradation and metabolism of xenobiotics, lipid metabolism, carbohydrate metabolism, and amino acid metabolism, and generates endoplasmic reticulum stress, inflammatory response, and immune toxicity. In summary, the results of this study provide basic data and a theoretical basis for further research on the molecular mechanism of DFB stress in carp.

Abstract Objective To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). Methods Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. Results Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p

Abstract Background Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. β-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of β-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization. Methods The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of β-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of β-elemene regulating M1/M2-like polarization in vitro. Results In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, β-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. β-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, β-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia. Conclusions These results indicated that β-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that β-elemene might serve as a promising drug for alleviating ischemic stroke injury.

ABSTRACT Background The objective of this study was to investigate the expression levels and biological significance of CKS2 in Burkitt cell lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL). Additionally, the potential synergistic anti‐tumor effects of CKS2 knockdown in combination with etoposide in BL and DLBCL were explored for the first time. Methods Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of CKS2 in BL and DLBCL. Specific shRNA sequences were designed to target CKS2 for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis. Results First, the study examined the increased transcriptional and protein levels of CKS2 in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated CKS2 expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that CKS2 functions were primarily linked to protein kinase regulatory activity, G1/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of CKS2 gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, CKS2‐shRNA induced G0/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of CKS2‐shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells. Conclusions Our findings suggest that CKS2 may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining CKS2‐shRNA and etoposide agents in the treatment of BL and DLBCL.

PurposeThe impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantitatively assess the effects of genetic polymorphisms on dabigatran esters in healthy Chinese subjects employed a population pharmacokinetic (PopPK) approach.MethodsIn total, 1,926 pharmacokinetic (PK) samples from 123 healthy individuals who were given 150 mg of dabigatran orally during a fasting state or postprandially were analyzed using the PopPK model. A two-compartment model with first-order absorption was found to adequately describe the PK data.ResultsThe results showed that covariates food intake and ABCB1 SNP rs4148738 were shown to have statistically significant impacts. Specifically, in postprandial administration increased lag time (ALAG) and clearance (CL) by 2.65% and 0.51%, respectively, and decreased absorption rate constant (KA) by 0.24%. Additionally, in subjects with CT genotype ABCB1 (rs4148738), the central ventricular volume of distribution (V2) was increased by 0.38%.ConclusionIn summary, the PopPK model developed in this study was robust and effectively characterized the pharmacokinetics of dabigatran in healthy Chinese adults, demonstrating that both food and ABCB1 genetic variation significantly influence the absorption and plasma concentration levels of dabigatran.

IntroductionSpinal cord injury (SCI) is a severe central nervous system disorder that results in significant sensory, motor, and autonomic dysfunctions. Current surgical techniques and high-dose hormone therapies have not achieved satisfactory clinical outcomes, highlighting the need for innovative therapeutic strategies.MethodsIn this study, we developed a Dual-Phase Silk Fibroin Methacryloyl (SilMA) hydrogel scaffold (DPSH) that incorporates PLGA microspheres encapsulating neurotrophin-3 (NT-3) and angiotensin (1-7) (Ang-(1–7)). The DPSH is designed for temporally controlled release of therapeutic agents to reduce inflammation during the acute phase of SCI and to promote neuronal differentiation and axonal regeneration in later stages.ResultsComprehensive characterization of the DPSH revealed a highly porous architecture, suitable mechanical properties for spinal cord tissue, and stability unaffected by the incorporation of microspheres and drugs. In vitro studies demonstrated that Ang-(1–7) significantly induced M2 microglia polarization by 1.8-fold (p < 0.0001), effectively reducing inflammation. Additionally, NT-3 enhanced neural stem cell differentiation into neurons by 3.6-fold (p < 0.0001). In vivo experiments showed that the DPSH group exhibited significantly higher Basso Mouse Scale (BMS) scores (p < 0.0001), enhanced motor function, reduced astrocyte scarring by 54% (p < 0.05), and improved neuronal survival and regeneration.DiscussionThese findings underscore the therapeutic potential of the DPSH scaffold for SCI repair, presenting a novel strategy to enhance neural recovery through a combination of immunomodulation and neuroprotection.

IntroductionThe purpose of this study was to explore the associations between ultra-processed foods (UPF), unprocessed or minimally processed foods (UMFs) with the quality of life (QoL) in Chinese adolescents.MethodsThe study included a baseline survey in 2021 (T1) and a follow-up survey in 2022 (T2), with a total of 3,206 participants, including 1,510 males (Age ± SE: 13.62 ± 1.69) and 1,696 females (Age ± SE: 14.09 ± 1.85). QoL was measured using the Quality of Life Scale for Children and Adolescents. All adolescents were asked to recall the foods they had eaten in the past week, which was classified using the NOVA system.ResultsInstant noodles, sugary drinks, and fried foods had a negative impact on adolescents’ QoL. Snacks or desserts only had a negative impact on the girls’ QoL. However, processed meats had a positive impact on the QoL of all adolescents. Fast food was beneficial for girls’ QoL. Fruits had a positive impact on the QoL of all adolescents. Green leafy vegetables, red and orange vegetables, fish, shrimp, or other seafood had a positive impact on the QoL of girls. Fresh poultry, pork, beef, and other meats had a positive impact on boys’ QoL. Soy products were detrimental to girls’ QoL. Tubers had a negative impact on boys’ QoL. Potatoes had a negative effect on the all adolescents’ QoL.DiscussionThis study further expands the understanding of the relationship between UPF, UMFs, and QoL. It provides new insights and evidence for improving the QoL of adolescents.

ObjectiveThe purpose of this study was to explore the key pathways leading to low quality of life in type 2 diabetes patients by means of network analysis, so as to provide the possibility of effective interventions.MethodsThe study involved 1,011 adult type 2 diabetes patients from a tertiary hospital in Harbin. Data was collected through questionnaires, and network analysis was performed using R software to assess the centrality and predictability of each node.Results“Depression” and “Submission” (weight = 0.26), “Depression” and “Physiological field” (weight = -0.16), exhibit the strongest associations. Overall, “Depression” has the highest weight in the association with diabetes symptom, regarding betweenness, “Depression” and “Submission” exhibit the highest scores, Furthermore, the analysis of closeness centrality reveals that “Depression” and “Submission” share the highest level of proximity, it suggests that they have the shortest distances to other network factors in our research network.ConclusionDepression and Submission are likely to be key factors affecting the quality of life of people with diabetes. Providing psychological support and scientific coping strategies for diabetes patients may be an effective way to help them live a better life.

BackgroundThis study aims to explore the effects of physical activity on adolescents' social skills and antisocial behavior, as well as gender and only child status differences among Chinese adolescents.MethodsWe used longitudinal data, collecting baseline data for 2021–2022 and follow-up in 2022–2023. A total of 3,206 students were enrolled, including 1,510 males (Age ± SE: 13.62 ± 1.69) and 1,696 females (Age ± SE: 14.09 ± 1.85), 1,339 only children (Age ± SE: 13.76 ± 1.95), and 1,867 non-only children (Age ± SE: 13.95 ± 1.66). The fixed effects model was used to identify the effects of different types of physical activity on adolescent social behavior and the heterogeneity analysis.Results(1) We found that skipping rope (β = 2.284, t = 5.76), walking (β = 3.495, t = 9.53), cycling (β = 1.271, t = 3.21), jogging (β = 2.614, t = 5.92), and badminton (β = 1.409, t = 2.96) had a positive impact on adolescents' social skills. Tag games (β = −1.615, t = −3.83), swimming (β = −2.862, t = −4.42), dancing (β = −1.11, t = −2.29), and skiing (β = −2.771, t = −3.27) had a negative impact on adolescents' social skills. Skipping rope (β = −1.596, t = −5.86), walking (β = −1.814, t = −7.44), cycling (β = −1.066, t = −4.07), and jogging (β = −1.617, t = −5.30) tended to reduce adolescents' antisocial behavior. Tag games (β = 1.685, t = 5.54), swimming (β = 0.947, t = 2.06), ice skating (β = 1.772, t = 2.71), and skiing (β = 1.468, t = 2.31) tended to increase adolescents' antisocial behavior. In addition, we found that these effects differ by gender and only child status. (2) Boys had significantly higher participation rates in activities. Only children had higher participation rates in skipping rope, baseball or softball, and volleyball, but non-only children had higher participation rates in walking, cycling, jogging, other aerobic exercises, and badminton. (3) Girls had higher social skills, but boys and only children had significantly higher rates of antisocial behavior.ConclusionOur results provide a novel understanding that can inform interventions and improvements in social behavior among Chinese adolescents. Stakeholders such as educators, policymakers, and health professionals can develop more tailored and effective strategies to promote positive social development among adolescents.

BackgroundPathologic myopia (PM) associated with myopic maculopathy (MM) is a significant cause of visual impairment, especially in East Asia, where its prevalence has surged. Early detection and accurate classification of myopia-related fundus lesions are critical for managing PM. Traditional clinical analysis of fundus images is time-consuming and dependent on specialist expertise, driving the need for automated, accurate diagnostic tools.MethodsThis study developed a deep learning-based system for classifying five types of MM using color fundus photographs. Five architectures—ResNet50, EfficientNet-B0, Vision Transformer (ViT), Contrastive Language-Image Pre-Training (CLIP), and RETFound—were utilized. An ensemble learning approach with weighted voting was employed to enhance model performance. The models were trained on a dataset of 2,159 annotated images from Shenzhen Eye Hospital, with performance evaluated using accuracy, sensitivity, specificity, F1-Score, Cohen’s Kappa, and area under the receiver operating characteristic curve (AUC).ResultsThe ensemble model achieved superior performance across all metrics, with an accuracy of 95.4% (95% CI: 93.0–97.0%), sensitivity of 95.4% (95% CI: 86.8–97.5%), specificity of 98.9% (95% CI: 97.1–99.5%), F1-Score of 95.3% (95% CI: 93.2–97.2%), Kappa value of 0.976 (95% CI: 0.957–0.989), and AUC of 0.995 (95% CI: 0.992–0.998). The voting ensemble method demonstrated robustness and high generalization ability in classifying complex lesions, outperforming individual models.ConclusionThe ensemble deep learning system significantly enhances the accuracy and reliability of MM classification. This system holds potential for assisting ophthalmologists in early detection and precise diagnosis, thereby improving patient outcomes. Future work could focus on expanding the dataset, incorporating image quality assessment, and optimizing the ensemble algorithm for better efficiency and broader applicability.

General anesthesia (GA) is an indispensable procedure necessary for safely and compassionately administering a significant number of surgical procedures and invasive diagnostic tests. However, the undesired stress response associated with GA causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons), is discovered to play a role in regulating sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVHCRH neurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVHCRH neurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.

Medicine food homology is a special existence that combines the therapeutic effects of medicine and the nutritional value of food, making it possible for people to obtain health through daily diet. In this review, not only the concept, origin, and development of medicine food homology were introduced, but also the basic information of 102 medicine food homology substances authoritatively released by the Chinese Ministry of Health were summarized in detail and classified according to different methods. Moreover, the major pharmacological activities and underlying mechanisms of these 102 substances were concluded, and several creative ideas were proposed for the future development of new medicine food homology substances in the future. Collectively, this review provided a scientific basis and theoretical reference for the further exploration and utilization of new medicine food homology substances. Overall, the study of medicine food homology possesses a broad development prospect and great application value.

China's status as the world's largest energy consumer highlights its pivotal role in global energy consumption and the urgency of enhancing its energy efficiency and renewable energy development. This study evaluates the influence of environmental regulations on green economic growth in China, with a focus on renewable energy and energy efficiency, from 2000 to 2023 across 30 provinces. Using the Metafrontier-Global-SBM super-efficient DEA model, the research measures green economic development through the lens of energy efficiency. An enhanced fuzzy comprehensive assessment gauges the stringency of environmental regulations. To explore non-linear impacts, regional spillover, and feedback effects, a spatial econometric model was applied. The results reveal a U-shaped non-linear relationship between environmental regulations and green economic growth, with significant spatial feedback and regional spillover effects. Environmental regulations are also shown to have a substantial positive influence on the development of renewable energy, a critical driver of green economic growth. Policy implications suggest that strengthening environmental regulations could accelerate renewable energy adoption and foster sustainable economic growth across regions in China.

Abstract Sepsis is responsible for approximately 5.3 million deaths globally each year. Here, we constructed hierarchical chitin microspheres loaded with MOF‐919 (Ch/metal–organic frameworks [MOFs]) for the rapid and efficient removal of lipopolysaccharide (LPS) in complex blood environments. Furthermore, abundant active sites on MOF‐919(Sc) also enable a record‐high adsorption capacity of 9.56 mg/g in biomass‐based adsorbents due to the coordination interactions between endotoxin and MOF‐919(Sc). The LPS level of sepsis rabbits was less than 2 EU/mL (clearance rate >95%) after 90‐min hemoperfusion, showing no adverse effect on the rabbit organs. Additionally, compared to the commonly used LPS scrubber Toraymyxin (polymethyl methacrylate), the chitin adsorbent is significantly more cost‐effective and environmentally friendly. The preparation strategy for hierarchical porous microspheres offers notable advantages in designability, recyclability, and renewability, providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.

Abstract This research delves into the effects of 2D layers on the functionality of 3D perovskite using lock‐in amplifier‐based in situ surface photovoltage (SPV) and its phase spectroscopy, with an emphasis on elucidating the connection between the tuning of dipole moments and the photocurrent hysteresis. Conventionally, the SPV of a perovskite/hole transport layer is observed to diminish as positive bias escalates. However, this trend is reversed in the case of 3D perovskite samples, where an augmentation in SPV is noted under positive bias. Notably, 3D/2D perovskite structures initially show a decrease, then an increase in SPV as bias intensifies, a phenomenon more pronounced with larger dipole moments in 2D. However, there is no linear relationship between the dipole moment and the hysteresis factor. Furthermore, using in situ light‐chopping‐frequency‐modulated SPV and Kelvin Probe Force Microscopy, it is revealed that the dipole fields of 2D layers can hinder ion migration. This leads to efficient hole transfer and minimal photocurrent hysteresis in 3D/2D perovskites, providing strong evidence for the underlying cause of hysteresis. Additionally, these findings suggest intricate interplays among the external electric field, interface dipole moments, and surface photovoltaics, offering significant insights into perovskite optoelectronics.