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The process of creative problem-solving (CPS) commonly demands that individuals consciously or unconsciously integrate creative ideas from a vast array of diverse information. Using a masked priming paradigm and the Chinese remote associates test (RAT), this study provides innovative behavioral evidence for the integration of multiple unconscious stimuli during CPS. In Experiment 1, three masked Chinese characters were simultaneously presented in the RAT, the first and third characters could be combined to form an answer. Two Chinese two-character words were presented in parallel, each containing the answer in Experiment 2, and required the complete word information to be split and subsequently re-integrated in a more complex manner than in Experiment 1. Interestingly, in both the experiments, multiple unconsciously processed stimuli generated a priming effect on creative performance. Specifically, a positive priming effect was observed in response to the difficult RATs, whereas a negative priming effect was observed in response to the easy RATs. Overall, our study verified that semantic integration between different unconsciously perceived stimuli can occur, which provides insights into the mechanisms underlying unconscious priming effects and contributes to a better understanding of how creative cognitive processing is influenced by multiple types of unconscious information.

Abstract Purpose Although photothermal therapy (PTT) can induce antitumour immunity, the mechanisms underlying its effects in pancreatic cancer (PC) require further exploration. In this study, the mechanism of action of PTT and its connection to pyroptosis as well as the therapeutic potential of PTT alone and in combination with STING agonists, were investigated. In addition, a biomarker of PC was found to stratify patients who are suitable for PTT. Experimental design We explored whether PTT can induce pyroptosis in vitro and evaluated the therapeutic efficacy and antitumour immunity-inducing ability of PTT combined with STING agonist (c-di-GMP) as immune adjuvant in vivo in PC. We also evaluated gasdermin D (GSDMD) expression in tumour tissues and investigated drug sensitivity in patient-derived organoids (PDOs) with differential GSDMD expression. Results Our study demonstrated that local PTT induces pyroptosis via the caspase-1/GSDMD pathway and elicits antitumour immunity. PTT combined with a STING agonist exhibits better therapeutic efficacy than PTT alone while limiting distant tumour metastasis, and enhances the immune response by promoting dendritic cell maturation, increasing the frequency of tumour infiltrating T cells, and converting macrophages from the M2 to the M1 phenotype. In addition, we found that GSDMD is highly expressed in tumour tissues and that overexpression of GSDMD in PC might suggest increased resistance to chemotherapy and the potential benefits of local therapy. We further confirmed that PDOs with higher GSDMD expression are less sensitive to a chemotherapeutic agent (5-Fluorouracil) than PDOs with lower GSDMD expression, making GSDMD a new biomarker for identifying patients who may benefit from PTT. Conclusions In this work, c-di-GMP was used as an immune adjuvant for PTT to treat PC for the first time, and the results provide clues for the development of novel combination immunotherapies that simultaneously suppress primary tumours and distant metastases. GSDMD has great potential as a new biomarker for the selection of individualized treatment modalities.

Abstract Background The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a potential biomarker for chronic disease outcomes. Cognitive impairment is a major contributor to mortality in older adults. However, the combined effect of NHR and cognitive function on all-cause mortality remains unclear. This study aims to investigate the joint impact of NHR and cognitive impairment on all-cause mortality in this population. Methods We analyzed participants in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Participants were grouped according to NHR levels, DSST scores, and the combined NHR and DSST. Weighted Cox regression models assessed the association between NHR, cognitive impairment, and all-cause mortality. Weighted Kaplan-Meier curves estimated survival probabilities. Results The study involved 1,486 participants (weighted sample was 54,078,084) aged 60 years and older, of whom 81.76% (n = 1,180) survived and 18.24% (n = 306) died by the end of follow-up. The median follow-up time was 78 months (IQR: 68–94). Weighted multivariable Cox regression revealed that high NHR (HR = 1.82, 95% CI: 1.21–2.74; P = 0.004), cognitive impairment (HR = 1.87, 95% CI: 1.25–2.79; P = 0.002), and the combination of high NHR and cognitive impairment (HR = 2.98, 95% CI: 1.45–6.14; P = 0.003) were independently associated with higher all-cause mortality, after full adjustment in model 3. Kaplan-Meier curves revealed significant survival differences, with the highest survival rate in the NHR Low & Normal cognition and the lowest in the NHR High & Cognitive impairment (P

Abstract Cancer-associated fibroblasts (CAFs) are highly heterogeneous cells and important components of the breast tumor microenvironment (TME). However, their role and clinical value in ER-positive breast cancer have not been fully clarified. Our study aims to comprehensively characterize the heterogeneity, potential biological functions, and molecular mechanisms of CAFs in ER-positive breast cancer within the tumor microenvironment using multi-omics data, to provide new strategies for the diagnosis and treatment of ER-positive breast cancer patients. In this study, we found that COL1A2(+) MMP1(+) and COL1A2(+) MMP1(-) CAFs were associated with unfavorable prognosis. The dynamic evolution and cell-cell communications of CAFs were analyzed, revealing that COL1A2(+) MMP1(+/-) CAFs show extensive crosstalk with tumor-associated macrophages (TAMs), contributing to an immunosuppressive TME. Moreover, the somatic mutation of TP53 may be a potential indicator for evaluating the infiltration of COL1A2(+) MMP1(+/-) CAFs. Finally, an MRI-based radiomic model was constructed to estimate the abundance of these CAFs. In conclusion, our findings provide a theoretical basis for targeting CAFs and offer a noninvasive approach to evaluate the infiltration level of COL1A2(+) MMP1(+/-) CAFs.

Abstract Introduction This study aimed to examine the interactions between abortion stigma and depressive symptoms among women who underwent termination of pregnancy for fetal anomalies over time. Methods This study is a longitudinal, observational study with two measurement points. A total of 241 women with fetal anomalies filled out the Individual Level Abortion Stigma Scale and the Edinburgh Postnatal Depression Scale before and after terminating pregnancy. Cross-lagged panel analysis was conducted to analyze the interactions between abortion stigma and depressive symptoms over time. Results The level of abortion stigma before terminating pregnancy positively influenced depressive symptoms after terminating pregnancy (β = 0.12, P

Metamaterials with active tunability of electromagnetic response have attracted much attention due to their flexibility and applicability in a wide range of optoelectronic applications. In this study, a mid-infrared (MIR) H-shaped metamaterial absorber (HMA) with high tunability is proposed. The structure of HMA is composed of one longitudinal and two transverse metal bars, forming an H-shaped resonator. By varying structural parameters, the HMA achieves perfect triple-band absorption. The resonant intensities of first and second resonances can be modulated linearly at the wavelength of 5.3 μm, while the resonant intensity of third resonance can be kept as stable at the wavelength of 7.3 μm. By moving the transverse metal bar, the maximum tuning range of resonance is 290 nm. Due to the non-rotationally symmetric configuration of HMA, it exhibits polarization-dependence characteristic. HMA exhibits the switchable function from triple-resonance to double-resonance. These results prove that the proposed HMA can be used for applications in gas sensing, polarization controlling, and IR filtering fields.

Abstract Background Mango is an economically important fruit tree in many regions of the world, but is highly susceptible to mango leaf spot disease, caused by Alternaria species. How to manage this disease has been a challenge and therefore understanding the regulation of host molecular components in response to pathogen infection is necessary. In this study, we conducted a comprehensive proteomic analysis of mango leaves upon inoculation with the leaf spot pathogen A. alternata. Results Determination of enzyme activity revealed a significant accumulation of cell-wall degrading enzymes cellulase and β-Glucosidase in pathogen inoculated mango leaves. A total of 472 differentially expressed proteins (DEPs) were detected in the proteome data with significant up-regulation of GO terms associated with response to fungus infection. The significantly downregulated proteins during pathogen invasion and colonization were involved in the photosynthesis, phenylpropanoid, flavonoid biosynthesis, and phenylalanine metabolism pathway. The significantly upregulated proteins belonged to tyrosine metabolism and MAPK signalling pathway, signifying their crucial role in host resistance to leaf spot pathogen. Conclusion Our finding provide useful data on differential expression of proteins for designing novel management strategies to specifically target mango host defense components to achieve the best control of leaf spot disease in mango.

Abstract Peptidoglycan recognition proteins (PGLYRPs) are implicated in the control of the intestinal microbiota; however, molecular requirements for peptidoglycan (PGN) binding and receptor signaling mechanisms remain poorly understood. Here we show that PGLYRP1 is a receptor for the disaccharide motif of lysine N-acetylglucosamine N-acetylmuramic tripeptide (GMTriP-K). PGLYRP1 is required for innate immune activation by GMTriP-K but not muramyl dipeptide (MDP). In macrophages, intracellular PGLYRP1 complexes with NOD2 and GEF-H1, both of which are required for GMTriP-K-regulated gene expression. PGLYRP1 localizes to the endoplasmic reticulum and interacts at the Golgi with NOD2 upon GMTriP-K stimulation. PGLYRP1 and dependent gene expression signatures are induced in both mouse intestinal inflammation and human ulcerative colitis. Importantly, PGLYRP1 activation by GMTriP-K can result in the protection of mice from TNBS-induced colitis. Mammalian PGLYRPs can function as intracellular pattern recognition receptors for the control of host defense responses in the intestine.

Intelligent health management is a crucial countermeasure to solving public health problems. By utilizing high-quality medical resources from a Third-Grade First Class Hospital, this study is able to solve prominent health problems in China, and it also creates medical knowledge bases and model bases. By taking advantage of intelligent additional features including self-testing health, risk estimation, health education, assessment, intelligent consultation, comprehensive intervention, and contracted doctor services, 40 statutory infectious diseases are monitored and warned early, and 260 common diseases are managed intelligently. The insured population can access health assessment, intelligent consultation, comprehensive intervention, and contracted doctor services through this research platform. The service management process is completed by these functions, which include health assessments, health classification management, personalized health plans, and health intervention to improve health status, decrease disease incidence rates, and improve health levels.

Abstract Background Insulin resistance, represented by increased triglyceride-glucose (TyG) index levels, shows interplay with visceral obesity and together promotes cardiovascular diseases and mortality. However, significant controversies exist regarding whether modified TyG indices, such as TyG-BMI, TyG-WC, and TyG-WHtR, outperform the TyG index in predicting cardiovascular outcomes. We aimed to explore whether there was a synergistic effect of a body shape index (ABSI), a better parameter reflecting visceral obesity, and the TyG index on cardiovascular mortality. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 of 17,329 individuals. The associations of the TyG index and ABSI with cardiovascular mortality were investigated via Cox regression analysis and restricted cubic splines. Receiver operating characteristic (ROC) curve analysis was performed to compare the predictive value. Mediation analysis was used to explore the potential mediator. Results A total of 673 (3.9%) cardiovascular deaths occurred during a median follow-up of 8.92 years. Individuals with high TyG and high ABSI (TyG > 9.04 and ABSI > 0.085) were at the highest cardiovascular mortality risk both in individuals with (HR = 1.714, 95% CI 1.123–2.616) and without diabetes (HR = 1.402, 95% CI 1.003–1.960), suggesting a synergistic effect. Next, we multiplied these two indicators and established TyG-ABSI. It showed a J-shaped relationship and a positive linear relationship with cardiovascular mortality in individuals with and without diabetes, respectively. Arterial stiffness, represented by estimated pulse wave velocity, partially mediated the effect of TyG-ABSI on cardiovascular mortality, with a mediation proportion of 42.7%. The predictive value of TyG-ABSI was greater than that of the TyG index, TyG-BMI, TyG-WC, and TyG-WHtR (Harrell’s C-index: 0.710 vs 0.623 vs 0.539 vs 0.612 vs 0.622, all p

Abstract This study aimed to evaluate the effectiveness of a new combined treatment approach using arthrocentesis, hyaluronic acid (HA) injection, mandibular manipulation (MM), and the Twin-Block appliance (TBA) for managing acute anterior disc displacement without reduction (ADDwoR). A retrospective cross-sectional study was designed. Thirty-seven patients (38 joints) diagnosed with acute ADDwoR were treated with arthrocentesis plus HA combined with MM and TBA in turn from January 2022 to December 2023. The maximum mouth opening (MMO), visual analogue scale (VAS) pain score, condyle/disc position were measured and comparatively analyzed at baseline and one week, three and six months post-treatment. Analysis of variance, Dunnett’s T3 analysis, and paired samples t-tests were conducted for statistical analyses setting the threshold for statistical significance at P

AIM: To investigate the effect of skullcapflavone II (SCF-II) on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta (TGF-β) in human corneal epithelial cells (HCECs), as well as to identify the signaling pathways that may be involved. METHODS: HCECs were cultured in vitro. At a SCF-II (5, 10 µmol/L) dose, cell viability was analysed with a cell counting kit-8 (CCK-8) assay, and cell migration was monitored with wound healing and Transwell migration assays. There were 4 groups: SCF-II, TGF-β, SCF-II+TGF-β and Control. Western blotting and immunofluorescence were performed to show the expression of EMT markers and the translocation of nuclear factor kappa-B (NF-κB) into the nucleus in the 4 groups. RESULTS: Treatment with SCF-II decreased HCEC viability in a dose-dependent manner. A concentration below 10 µmol/L did not present obvious cell toxicity, and survival rates were more than 70% at 48h. Treatment with SCF-II (5 and 10 µmol/L) significantly impeded migration in wound healing and Transwell migration assays (P

Abstract Background To evaluate the clinical diagnostic value of third-generation dual-source CT for pulmonary embolism, focusing on the optimization of dual-source CT scanning with dynamic reconstruction in acute pulmonary embolism (PE) and various imaging manifestations. Methods Eighty-two patients with pulmonary embolism were enrolled and randomly divided into standard CT angiography (SCTA) and dynamic CT angiography (DCTA). DCTA patients were divided into dynamic CT angiography arterial phase (DCTAa), time phase Angiography reconstruction (TMIP-CTA), and 4D noise reduction TMIP-CTA according to the image reconstruction. The region of interest was selected in the region of the pulmonary trunk and its branches, respectively. The vessel CT value and image background noise (IN) of each subgroup were also determined, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Simultaneously two radiologists performed a subjective evaluation of the quality of the picture images. Results The DCTA group had a lower contrast dose than the SCAT group, but the vessel CT value, IN, CNR, and SNR were significantly higher in the DCTA group compared with the SCTA group. CT of the vascular lumen was generally higher in all subgroups of DCTA than in SCTA, with the highest in the TMIP-CIA group. IN was significantly higher in both the DCTAa and TMIP-CTA groups than in the SCTA group. SNR and CNR were elevated in TMIP-CTA and 4D noise reduction TMIP-CTA compared to the SCTA group. In addition, the subjective image quality scores of the DCTA group were significantly higher than those of SCTA, and the 4D noise reduction TMIP-CTA had the most. However, the ED of the SCTA group was lower than that of the DCTA group. Conclusion 4D noise reduction TMIP-CTA based on DCTA reconstruction significantly improves the quality of pulmonary artery CTPA images and increases the clinical diagnostic rate, with potential for clinical dissemination.

Abstract Background Functional constipation (FC) significantly impacts children’s health. This study investigates the prevalence and microbiota characteristics of FC in children aged 0–4 years in Zunyi area. Methods From October to December 2023, 2039 children aged 0–4 years in Zunyi were selected using stratified sampling and cross-sectional survey methods. A questionnaire based on Rome IV diagnostic criteria was used. Twenty-nine children with FC were randomly selected as the functional constipation group (FCG), and 26 healthy children, matched for age, sex, and area, were selected as the control group (CG). Results A total of 2051 questionnaires were collected, with 2039 valid responses. Among them, 151 children had FC, resulting in a prevalence rate of 7.4%. The prevalence rates in boys and girls were 6.6% and 8.5%, respectively, with no significant gender difference (P > 0.05). Alpha diversity analysis revealed higher richness and diversity of intestinal flora in the FCG compared to the CG. At the phylum level, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes were dominant in both groups. The FCG showed a higher relative abundance of Firmicutes, Actinobacteria, and Proteobacteria compared to the CG (P

Abstract Background Mitochondrial dysfunction and neuronal damage are major sign of cytopathology in Huntington’s disease (HD), a neurodegenerative disease. Ubiquitin specific peptidase 11 (USP11) is a deubiquitinating enzyme involved in various physiological processes through regulating protein degradation. However, its specific role in HD is unclear. Methods To interfere with USP11 expression, adeno-associated viruses 2 containing USP11-specific shRNA were injected into the bilateral striatum of 12-week-old R6/1 and WT mice. In vitro, the inducible PC12 cell model of HD was used in which the expression of an N-terminal truncation of huntingtin, with either wild type (Q23) or expanded polyglutamine (Q74) can be induced by the doxycycline. USP11 was knocked down to study its role in HD. The protein expression patterns in Q74 cells were quantified by label-free proteomics to further explore the target protein of USP11. Detecting the association between USP11 and Phosphatase and Tensin Homolog (PTEN) through Co-IP. Results Herein, USP11 was found to be upregulated in the striatum of R6/1 mice (an HD model with gradual development of symptoms) in an age-dependent manner. The spontaneous HD was alleviated by silencing USP11, as evidenced by improved locomotor activity and spatial memory, attenuated striatal atrophy in R6/1 mice, reduced accumulation of mutant huntingtin protein, and restored mitochondrial function in vitro and in vivo. The results of label-free proteomics revealed a significant change in the protein expression profile. Through functional enrichment, we focused on PTEN, known as a negative regulator of the AKT pathway. We demonstrated that USP11 downregulation promoted ubiquitination modification of PTEN and activated the AKT pathway, and PTEN overexpression reversed the effects of USP11 knockdown. Conclusions Collectively, USP11 knockdown protects R6/1 mouse neurons from oxidative stress by alleviating mitochondrial dysfunction, thereby preventing the HD progression. This is achieved by inhibiting PTEN expression, which in turn activates the AKT pathway. This study suggests that USP11-PTEN-AKT signaling pathway may be a new attractive therapeutic target for HD.

Abstract Ferroptosis and autophagy are two main forms of regulated cell death (RCD). Ferroptosis is a newly identified RCD driven by iron accumulation and lipid peroxidation. Autophagy is a self-degradation system through membrane rearrangement. Autophagy regulates the metabolic balance between synthesis, degradation and reutilization of cellular substances to maintain intracellular homeostasis. Numerous studies have demonstrated that both ferroptosis and autophagy play important roles in cancer pathogenesis and cancer therapy. We also found that there are intricate connections between ferroptosis and autophagy. In this article, we tried to clarify how different kinds of autophagy participate in the process of ferroptosis and sort out the common regulatory pathways between ferroptosis and autophagy in cancer. By exploring the complex crosstalk between ferroptosis and autophagy, we hope to broaden horizons of cancer therapy.

Abstract Ceftazidime-avibactam (CZA) is currently one of the last resorts used to treat infections caused by carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. However, KPC variants have become the main mechanism mediating CZA resistance in KPC-producing gram-negative bacteria after increasing the application of CZA. Our previous study revealed that CZA-resistant KPC-33 had emerged in carbapenem-resistant P. aeruginosa (CRPA) and had resulted in death due to hypervirulence and extensive drug resistance; however, the evolutionary path of KPC-33-producing CRPA has not been investigated. Here, we observed the emergence of bla KPC-33 in CRPA under drug pressure, leading to resistance to CZA. We further elucidated the pathway of resistance development due to bla KPC mutations in P. aeruginosa. Three KPC-producing P. aeruginosa (KPC-PA) strains (including one bla KPC-33-positive strain and two bla KPC-2-positive strains) were successively isolated from a hospitalized patient. The bla KPC-33-positive CZA-resistant strain SRPA0656 (CZA MIC >128 μg/mL, imipenem MIC = 32 μg/mL) was isolated after the bla KPC-2-positive P. aeruginosa SRP2863 (CZA MIC = 1 μg/mL, imipenem MIC >128 μg/mL) was treated with CZA. The subsequent use of carbapenems to treat the infection led to the re-emergence of the KPC-2-producing strain SRPA3703. Additionally, we collected four other KPC-33-producing P. aeruginosa strains. Antimicrobial susceptibility testing revealed that all the KPC-33-bearing P. aeruginosa strains in this study were multidrug-resistant but susceptible to colistin and amikacin. Whole-genome sequencing indicated that bla KPC-33 was located on two Tn4401-like transposons contained in the plasmids and that most of these plasmids could be transferred into P. aeruginosa PAO1Rif isolates. Growth rate determination demonstrated that the relative growth rate of P. aeruginosa harboring bla KPC-33 was faster than that of P. aeruginosa harboring bla KPC-2 in the logarithmic phase. Global phylogenetic analysis revealed that most KPC-PA strains were isolated from China and the USA. MLST revealed that the most common ST in KPC-PA was ST463, which was detected only in China, and that all the strains carried bla KPC-2 or its derivatives. These results indicated that the use of CZA for the treatment of KPC-2-producing P. aeruginosa may have contributed to the evolution of KPC-33. The widespread dissemination of KPC-PA (especially the ST463) and Tn4401 transposons may increase the spread of CRPA isolates carrying bla KPC-33. Close attention to the development of resistance to CZA during clinical treatment of CRPA infection and monitoring CZA-resistant strains is necessary to prevent further spread.

The paper addresses the challenges of task migration and resource allocation in heterogeneous cloud–edge environments, where dynamic and stochastic conditions complicate efficient scheduling. To tackle this, the authors propose a novel scheduling algorithm combining soft actor–critic (SAC) agent with masked layer and graph convolutional network (GCN), namely MGSAC algorithm. MGSAC utilizes GCN to extract hidden structural features from the environment, enabling better adaptation to dynamic changes. Additionally, a learnable mask layer filters out ineffective actions, refining the selection of scheduling strategies and improving overall performance. By evaluating MGSAC on the real-world Bit-Brain dataset and simulating it using Cloud-Sim, experimental results demonstrate its superiority over existing algorithms in energy consumption, task response time, task migration time, and task Service-Level-Agreement violations rate, showcasing its effectiveness in real-world scenarios.

ObjectiveTo investigate the adherence to four healthy lifestyle factors among residents aged 35 – 75 years in South China and to identify the influencing factors, providing a reference for promoting healthy lifestyles in this region. MethodsA cross-sectional survey was conducted from September 2015 to November 2022 using a typical sampling method in South China. A total of 289 937 residents aged 35 – 75 years from Guangdong province, Guangxi Zhuang Autonomous Region, and Hainan province were included. The adherence to four healthy lifestyle factors, namely non-smoking, no or moderate alcohol consumption, adequate physical activity, and a healthy diet, was analyzed. Multivariable unconditional logistic regression models were used to identify the influencing factors. ResultsAmong the 80,385 residents aged 35 – 75 years included in the final analysis, the number of participants adhering to non-smoking, no or moderate alcohol consumption, adequate physical activity, a healthy diet, and all four healthy lifestyle factors were 66 765, 78 576, 23 807, 18 391, and 6 707, respectively. The corresponding adherence rates were 83.1%, 97.7%, 29.6%, 22.9%, and 8.3%, and the standardized adherence rates were 77.95%, 97.26%, 27.66%, 23.42%, and 7.31%, respectively. Multivariable unconditional logistic regression analysis showed that female residents, those aged 70 – 75 years, those with a college degree or higher, those who were married, and those with a history of myocardial infarction/coronary revascularization/stroke were more likely to adhere to non-smoking. Residents aged 40 – 59 years, those with a junior high school education, farmers, rural residents, those with an annual household income of 10 000 – 50 000 yuan, and those with a history of hypertension/diabetes were less likely to adhere to non-smoking. Female residents, those aged 70 – 75 years, and those who were married were more likely to adhere to no or moderate alcohol consumption. Residents aged 50 – 59 years, farmers, and rural residents were less likely to adhere to no or moderate alcohol consumption. Female residents, those aged 50 – 75 years, those with a high school education or higher, those with an annual household income of > 50 000 yuan, and those with a history of hypertension/diabetes or myocardial infarction/coronary revascularization/stroke were more likely to adhere to adequate physical activity. Residents aged 40 – 49 years, those with a junior high school education, farmers, rural residents, and those with an annual household income of 10 000 – 50 000 yuan were less likely to adhere to adequate physical activity. Female residents, those aged 50 – 75 years, those with a high school education or higher, and those with an annual household income of > 50 000 yuan were more likely to adhere to a healthy diet. Residents with a junior high school education, farmers, rural residents, and those with social medical insurance were less likely to adhere to a healthy diet. Female residents, those aged 50 – 75 years, those with a high school education or higher, those with an annual household income of > 50 000 yuan, and those with a history of myocardial infarction/coronary revascularization/stroke were more likely to adhere to all four healthy lifestyle factors. Residents aged 40 – 49 years, those with a junior high school education, farmers, rural residents, and those with an annual household income of 10 000 – 50 000 yuan were less likely to adhere to all four healthy lifestyle factors. ConclusionsThe adherence rates to non-smoking, no or moderate alcohol consumption, adequate physical activity, and a healthy diet were low among residents aged 35 – 75 years in South China. Gender, occupation, residence, and history of myocardial infarction/coronary revascularization/stroke were common influencing factors for adherence to the four healthy lifestyle factors.

Abstract Background Low back pain is a major disorder that causes disability and is strongly associated with intervertebral disc degeneration (IDD). Because of the limitations of contemporary interventions, stem cell transplantation (SCT) has been increasingly used to regenerate degenerative discs. Nevertheless, analyses of high-impact papers in this field are rare. This study aimed to determine and analyze the 100 highest-cited documents on SCT in IDD. Methods The 100 highest-cited documents were retrieved from the Web of Science (WoS) database. Descriptive statistics were calculated and correlation analysis was conducted to determine the relationship between WoS citations, the Altmetric Attention Score (AAS), and Dimensions citations. Results The citation counts of the top 100 most cited papers ranged from 13 to 372. These studies were conducted in 17 countries and were published in 48 journals between 2003 and 2021. The top three contributing countries were the China (31), United States (22), and Japan (14). Bone marrow-derived stem cells were the most common type of stem cells (70.00%), followed by adipose-derived stem cells (13.75%), and nucleus pulposus-derived stem cells (7.50). Rabbit was the most studied species (41.25%), followed by rat (21.25%), human (13.75%), sheep (8.75%), dog (8.75%), and pig (6.25%). Tokai University School of Medicine (11) had the largest number of documents, followed by The University of Hong Kong (8), and Southeast University (4). Sakai D (10) was the most fruitful author, followed by Cheung KMC (6), Melrose J (3), Pettine K (3), Lotz JC (3), and Murphy MB (3). We observed a very high correlation between the WoS and Dimensions citations (p

Abstract The pathogenesis of breast cancer is still unclear. Small RNAs associated with extracellular vesicles (EVs) have been found to be involved in tumor development. It is important to explore the role of EVs small RNAs in breast cancer. In this study, we established a plasma EVS-associated small RNA dataset that included 120 women who were positive for breast cancer screening and 60 women who were negative. These small RNA included 2656 miRNAs, 728 piRNAs, and 154 tsRNAs. These data provide a reference for researchers to explore molecular diagnostic biomarkers for early breast lesions.

Abstract Background The hippocampus is associated with mood disorders, and the activation of quiescent neurogenesis has been linked to anxiolytic effects. Near-infrared (NIR) light has shown potential to improve learning and memory in human and animal models. Despite the vast amount of information regarding the effect of visible light, there is a significant gap in our understanding regarding the response of neural stem cells (NSCs) to NIR stimulation, particularly in anxiety-like behavior. The present study aimed to develop a new optical manipulation approach to stimulate hippocampal neurogenesis and understand the mechanisms underlying its anxiolytic effects. Methods We used 940 nm NIR (40 Hz) light exposure to stimulate hippocampal stem cells in C57BL/6 mice. The enhanced proliferation and astrocyte differentiation of NIR-treated NSCs were assessed using 5-ethynyl-2’-deoxyuridine (EdU) incorporation and immunofluorescence assays. Additionally, we evaluated calcium activity of NIR light-treated astrocytes using GCaMP6f recording through fluorescence fiber photometry. The effects of NIR illumination of the hippocampus on anxiety-like behaviors were evaluated using elevated plus maze and open-field test. Results NIR light effectively promoted NSC proliferation and astrocyte differentiation via the OPN4 photoreceptor. Furthermore, NIR stimulation significantly enhanced neurogenesis and calcium-dependent astrocytic activity. Moreover, activating hippocampal astrocytes with 40-Hz NIR light substantially improved anxiety-like behaviors in mice. Conclusions We found that flickering NIR (940 nm/40Hz) light illumination improved neurogenesis in the hippocampus with anxiolytic effects. This innovative approach holds promise as a novel preventive treatment for depression.

Abstract Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume. Diverse antigens, mRNAs, neurotransmitters, and post-translational modifications are well-preserved and simultaneously visualized. INSIHGT also allows multi-round, highly multiplexed 3D molecular probing and is compatible with downstream traditional histology and nucleic acid sequencing. With INSIHGT, we map undescribed podocyte-to-parietal epithelial cell microfilaments in mouse glomeruli and neurofilament-intensive inclusion bodies in the human cerebellum, and identify NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate that INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies.

Since the outbreak of the Gaza conflict in October 2023, a severe humanitarian crisis has occurred across the entire Gaza Strip. Owing to the challenges of conducting traditional ground-based surveys in the region, satellite images have become critically important as an objective source of information. In response to the demands of humanitarian relief, this study utilized VIIRS, SDGSAT-1, and Yangwang-1 nighttime light (NTL) satellite images to provide a multi-scale assessment of the spatiotemporal dynamics of power supply in the Gaza Strip during the conflict. To reduce errors in quantitatively estimating power supply based on nighttime light, the quality of daily VIIRS NTL images was enhanced and radiometric intercalibrations were conducted between SDGSAT-1 and Yangwang-1 NTL images. The result indicates a severe disruption of power supply in the Gaza Strip as a consequence of the conflict. Specifically, the overall power supply had a sharp decline shortly after the outbreak of the conflict on 7 October 2023 and persisted in a downtrend during the conflict, culminating in a reduction of around 94% as of 1 March 2024. In contrast, the power supply in areas surrounding the Gaza Strip remained relatively stable during the conflict. On 2 December 2023, 24 municipalities were found to have significant reductions in power supply exceeding 90%, and around 95% of buildings had power losses of more than 75%. Furthermore, approximately 70% of hospitals and UNRWA schools in the Gaza Strip were identified to have power outages on 1 January 2024. Among the five governorates of the Gaza Strip, Rafah was the most resilient in terms of power supply during the conflict. This study could make a positive contribution to the timely assessments of the Gaza conflict and support the implementation of humanitarian relief efforts.

Abstract Proinsulin translation and folding is crucial for glucose homeostasis. However, islet β-cell control of Proinsulin translation remains incompletely understood. Here, we identify OSGEP, an enzyme responsible for t6A37 modification of tRNANNU that tunes glucose metabolism in β-cells. Global Osgep deletion causes glucose intolerance, while β-cell-specific deletion induces hyperglycemia and glucose intolerance due to impaired insulin activity. Transcriptomics and proteomics reveal activation of the unfolded protein response (UPR) and apoptosis signaling pathways in Osgep-deficient islets, linked to an increase in misfolded Proinsulin from reduced t6A37 modification. Osgep overexpression in pancreas rescues insulin secretion and mitigates diabetes in high-fat diet mice. Osgep enhances translational fidelity and alleviates UPR signaling, highlighting its potential as a therapeutic target for diabetes. Individuals carrying the C allele at rs74512655, which promotes OSGEP transcription, may show reduced susceptibility to T2DM. These findings show OSGEP is essential for islet β-cells and a potential diabetes therapy target.

Background There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM. Methods This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893). Results After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P

Abstract Background Exosome small RNAs are believed to be involved in the pathogenesis of cancer, but their role in breast cancer is still unclear. This study utilized machine learning models to screen for key exosome small RNAs and analyzed and validated them. Method Peripheral blood samples from breast cancer screening positive and negative people were used for small RNA sequencing of plasma exosomes. The differences in the expression of small RNAs between the two groups were compared. We used machine learning algorithms to analyze small RNAs with significant differences between the two groups, fit the model through training sets, and optimize the model through testing sets. We recruited new research subjects as validation samples and used PCR-based quantitative detection to validate the key small RNAs screened by the machine learning model. Finally, target gene prediction and functional enrichment analysis were performed on these key RNAs. Results The machine learning model incorporates six small RNAs: piR-36,340, piR-33,161, miR-484, miR-548ah-5p, miR-4282, and miR-6853-3p. The area under the ROC curve (AUC) of the machine learning model in the training set was 0.985 (95% CI = 0.948-1), while the AUC in the test set was 0.972 (95% CI = 0.882–0.995). RT-qPCR was used to detect the expression levels of these key small RNAs in the validation samples, and the results revealed that their expression levels were significantly different between the two groups (P

Abstract Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Abstract Background The persistently rising complication, pseudotumor, after hip arthroplasty required surgeons’ vigilance. Although the remaining controversial relationship between metal ions and pseudotumor, metal ion detection had been widely employed in clinic. The aim of this study is to evaluate the correlation between metal ions and pseudotumor, as well as the effectiveness of metal ion analysis in the screening and diagnosis of pseudotumor through systematic review and meta-analysis. Methods The Medline and Embase databases were searched for studies evaluating metal ions and patients with pseudotumors after hip arthroplasty. A systematic review of risk ratio and diagnostic performance for metal ions was conducted. Results Seven studies were included in the systematic review. The mean Methodological Index for Non-Randomized Studies (MINORS) score of the included studies was 19 (range, 14 to 22). Pooled risk ratio (RR) value was 2.01(95% CI: 1.25–3.24; P = 0.004) for cobalt ions level and 1.44 (95% CI: 1.10–1.88; P = 0.008) for chromium ions level. The pooled sensitivity, specificity and the area under the curve (AUC) for cobalt and chromium ions were determined to be 0.59, 0.82, 0.73 and 0.34, 0.82, 0.56, respectively. Conclusions The metal ions level has a low diagnostic value. It is of certain value for confirmation, but should not be used as a routine screening indicator. The diagnostic value of cobalt ions is higher than that of chromium. Level of Evidence: Diagnostic Level IV.

Abstract Background Mitochondrial calcium uniporter (MCU) plays pleiotropic roles in cellular physiology and pathology that contributes to a variety of diseases, but the role and potential mechanism of MCU in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) remain poorly understood. Methods and results Here, hepatic knockdown of MCU in C57BL/6J mice was achieved by tail vein injection of AAV8-mediated the CRISPR/Cas9. Mice were fed a Choline-deficient, L-amino acid-defined high-fat diet (CDAHFD) for 8 weeks to induce MASH and fibrosis. We find that expression of MCU enhanced in MASH livers of humans and mice. MCU knockdown robustly limits lipid droplet accumulation, steatosis, inflammation, and hepatocyte apoptotic death during MASH development both in vivo in mice and in vitro in cellular models. MCU-deficient mice strikingly mitigate MASH-related fibrosis. Moreover, the protective effects of MCU knockdown against MASH progression are accompanied by a reduced level of mitochondrial calcium, limiting hepatic oxidative stress, and attenuating mitochondrial dysfunction. Mechanically, RNA sequencing analysis and protein immunoblotting indicate that knockdown MCU inhibited the Hippo/YAP pathway activation and restored the AMP-activated protein kinase (AMPK) activity during MASH development both in vitro and in vivo. Conclusions MCU is up-regulated in MASH livers in humans and mice; and hepatic MCU knockdown protects against diet-induced MASH and fibrosis in mice. Thus, targeting MCU may represent a novel therapeutic strategy for MASH and fibrosis. Graphical Abstract

Lithium hexafluorophosphate (LiPF6), the most commonly used lithium battery electrolyte salt, is vulnerable to heat and humidity. Quantitative and qualitative determination the variation of LiPF6 have always relied on advanced equipment. Herein, we develop a fast, convenient, high-selective fluorescence detection method based on metal–organic cages (MOC), whose emission is enhanced by nearly 20 times in the presence of LiPF6 with good stability and photobleaching resistance. The fluorescent probe can also detect moisture in battery electrolyte. We propose and verify that the luminescence enhancement is due to the presence of hydrogen bond-induced enhanced emission effect in cages. Fluorescent excitation-emission matrix spectra and variable-temperature nuclear magnetic resonance spectroscopy are employed to clarify the role of hydrogen bonds in guest-loaded cages. Density functional theory (DFT) calculation is applied to simulate the structure of host-guest complexes and estimate the adsorption energy involved in the system. The precisely matched lock-and-key model paves a new way for designing and fabricating novel host structures, enabling specific recognition of other target compounds.

Abstract Background Recent magnetic resonance imaging (MRI) studies have established that brain iron accumulation might accelerate cognitive decline in Alzheimer’s disease (AD) patients. Both normal aging and AD are associated with cerebral atrophy in specific regions. However, no studies have investigated aging- and AD-selective iron deposition-related cognitive changes during normal aging. Here, we applied quantitative susceptibility mapping (QSM) to detect iron levels in cortical signature regions and assessed the relationships among iron, atrophy, and cognitive changes in older adults. Methods In this Taizhou Imaging Study, 770 older adults (mean age 62.0 ± 4.93 years, 57.5% women) underwent brain MRI to measure brain iron and atrophy, of whom 219 underwent neuropsychological tests nearly every 12 months for up to a mean follow-up of 2.68 years. Global cognition was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Domain-specific cognitive scores were obtained from MoCA subscore components. Regional analyses were performed for cortical regions and 2 signature regions where atrophy affected by aging and AD only: Aging (AG) -specific and AD signature meta-ROIs. The QSM and cortical morphometry means of the above ROIs were also computed. Results Significant associations were found between QSM levels and cognitive scores. In particular, after adjusting for cortical thickness of regions of interest (ROIs), participants in the upper tertile of the cortical and AG-specific signature QSM exhibited worse ZMMSE than did those in the lower tertile [ $$\:\beta\:$$ β = -0.104, p = 0.026; $$\:\beta\:$$ β = -0.118, p = 0.021, respectively]. Longitudinal analysis suggested that QSM values in all ROIs might predict decline in ZMoCA and key domains such as attention and visuospatial function (all p

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.