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Abstract Ongoing mass wasting through ice block falls is intensive at the north polar ice cap of Mars. We monitored how this activity is currently shaping the marginal steep scarps of the ice cap, which holds a record of the planet’s climate history. With AI-driven change detection between multi-temporal high-resolution satellite images, we created a comprehensive map of mass wasting across the entire North Polar Layered Deposits (NPLD). Our results show a more active erosion process than previously thought, with scarps retreating by up to ~3 m every kiloyear. The distribution of the active scarps indicates an ongoing asymmetric retreat of the already subcircular ice cap. The active scarps and the interior dune fields correlate strongly with exposures of the underlying, sandier Basal Unit (BU), providing evidence that erosion of the BU undermines the base of the NPLD. Moreover, ice block fall activity suggests potential areas where gypsum is released, given that the interior gypsum-bearing dune fields are located adjacent to these active scarps. Here, our study reveals the rates of present-day topographic change of the north polar ice cap, providing a valuable constraint for study of its past evolution.

Abstract Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00–21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.

Abstract The obese heart undergoes metabolic remodeling and exhibits impaired calcium (Ca2+) homeostasis, which are two critical assaults leading to cardiac dysfunction. The molecular mechanisms underlying these alterations in obese heart are not well understood. Here, we show that the Rab-GTPase activating protein AS160 is a lipid-responsive regulator of Ca2+ homeostasis through governing lysophosphatidylinositol metabolism and signaling. Palmitic acid/high fat diet inhibits AS160 activity through phosphorylation by NEK6, which consequently activates its downstream target Rab8a. Inactivation of AS160 in cardiomyocytes elevates cytosolic Ca2+ that subsequently impairs cardiac contractility. Mechanistically, Rab8a downstream of AS160 interacts with DDHD1 to increase lysophosphatidylinositol metabolism and signaling that leads to Ca2+ release from sarcoplasmic reticulum. Inactivation of NEK6 prevents inhibition of AS160 by palmitic acid/high fat diet, and alleviates cardiac dysfunction in high fat diet-fed mice. Together, our findings reveal a regulatory mechanism governing metabolic remodeling and Ca2+ homeostasis in obese heart, and have therapeutic implications to combat obesity cardiomyopathy.

Harm aversion is essential for normal human functioning; however, the neuroanatomical mechanisms underlying harm aversion remain unclear. To explore this issue, we examined the brain structures associated with the two distinct dimensions of harm aversion (harm action/outcome aversion) and the potential mediating role of the four aspects of empathy: fantasy, perspective-taking, empathic concern, and personal distress. A sample of 214 healthy young adults underwent structural magnetic resonance imaging. Voxel-based morphometry was used to assess regional gray matter volume (rGMV) and regional gray matter density (rGMD). Whole-brain multiple regression analysis revealed significant correlations between harm action aversion and rGMV/rGMD in various brain regions, including the inferior frontal gyrus (IFG) and precuneus for both rGMV and rGMD, the cerebellum for rGMV, and the superior frontal gyrus for rGMD. The rGMV/rGMD in the IFG and the rGMD in the primary somatosensory cortex (S1) were correlated with harm outcome aversion. Utilizing 10-fold balanced cross-validation analysis, we confirmed the robustness of these significant associations between rGMV/rGMD in these brain regions and harm action/outcome aversion. Importantly, mediation analysis revealed that empathic concern mediated the relationship between rGMV/rGMD in the precuneus and harm action aversion. Additionally, empathic concern, personal distress, and total empathy mediated the relationship between rGMD in the S1 and harm outcome aversion. These findings enhance our understanding of the neural mechanism of harm aversion by integrating insights from the brain structure, harm aversion, and the personality hierarchy models while also extending the frontal asymmetry model of Emotion

Undergraduate students (N = 165) completed an online survey about their experiences with the sudden transition to online learning, prompted by the COVID-19 pandemic. Results of multiple regression analyses suggested that satisfaction with the transition online, concerns about COVID-19, and computer time were associated with signs of distress (changes in grades, stress level, and depressive symptoms), after accounting for preference for online instruction, housing satisfaction, and other covariates. Students' responses to open-ended questions identified approaches employed by instructors that were perceived as helpful or unhelpful. Students advocated for fewer assignments, better communication, and greater empathy and understanding from their instructors.

Abstract Background Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear. Objective To investigate the topological organization of individual-level MBNs in pediatric GHD. Methods Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed. Results Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all P FDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all P FDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all P FDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected). Conclusion GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance.

Residential buildings have a significant potential for energy conservation. The building energy consumption process is a complex system influenced by several factors at climate, building system, and occupant levels. This study introduces a novel model based on a multi-agent system to systematically integrate these multiple influencing factors, simulate their interactions, and estimate the resultant cooling and heating energy with dynamic variations over years considered. The automatic dynamic energy simulation was conducted over 30 years considering four temporal parameters (i.e., outdoor temperature, heat transfer coefficient of the building envelope, household type, and behavior pattern of occupants). A case building was used to validate the model, and the dynamic annual results were quite different from the static ones. The dynamic cumulative cooling energy consumption during 31 years was 0.69 % lower than the static one, whereas dynamic cumulative heating energy was 7.53 % higher compared with static energy. It highlighted the importance of considering dynamic multi-agent interactions. Besides, the roles of multiple energy influencing factors and dynamic parameters were compared and discussed. This study provides critical insights into improving building energy performance and offers a rapid and automatic approach for dynamic energy simulation.

Background: Cuproptosis, one of the most recently discovered forms of cell death, is induced by the disruption of copper binding to the mitochondrial respiratory acylation components. However, the mechanism underlying cuproptosis in uveal melanoma (UM) has not yet been adequately studied. Methods: RNA and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed cuproptosis-related genes were identified by R software. A prognostic signature was constructed by applying LASSO regression and Cox regression models. The associations between the signature and the immune microenvironment, overall survival, and drug sensitivity were studied. In addition, qPCR and Western blotting were performed on UM cells and RPE cell lines to verify the expression levels of the genes encoding dihydrolipoamide dehydrogenase (DLD) and dihydrolipoamide S-succinyltransferase (DLST) in UM cases. Results: Using a cuproptosis-related prognostic signature, UM samples were classified into high- and low-risk groups. A significant difference in overall survival between the two risk groups was evident. Receiver operating characteristic curves demonstrated that the signature is a reliable predictor of prognosis. Immune cell infiltration, drug sensitivity, and immune checkpoint expression were analysed. Significant immune difference between the two high-risk groups was found, and the high expression of immune checkpoints in high-risk groups suggests significant immunotherapy potential. In addition, drug sensitivity analysis experiments suggest that erlotinib may be a potential treatment for high-risk patients. The results of in vitro experiments confirmed that DLD and DLST had higher expression levels in UM cell lines. Conclusions: The prognostic signature developed in this study is a reliable biomarker for predicting the prognosis of UM and may serve as a tool for personalised treatment of patients with UM.

ObjectiveTo evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved.MethodsMTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups.ResultsDADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p

Construction activities discharge considerable carbon emissions, causing serious environmental problems and gaining increasing attention. For the large-scale construction area, high emission intensity, and significant carbon reduction potential, embodied carbon emissions of buildings worth special studying. However, previous studies are usually post-evaluation and ignore the influences of project, construction and management. This paper focuses on critical building materials and adopts machine learning methods to realize carbon prediction at design stage. The activity data, including critical building materials, water, and energy consumption, is analyzed and 30 influencing factors at the project, construction, and management levels are identified. Three algorithms (artificial neural network, support vector regression and extreme gradient boosting) are used to develop machine learning models. The proposed methodology is applied to 70 projects in the Yangtze River Delta region of China. Results show that the established models achieved high interpretability (R2 >0.7) and small average error (5.33%), well proving theirs feasibility. Furthermore, an automated tool is developed to assist practitioners to predict the critical materials consumption and embodied carbon emissions conveniently. The proposed operable model and practical tool can efficiently support effective adjustments and improvement to reduce carbon in construction.

Abstract The breakthrough of programmed cell death protein 1 (PD‐1) blockade therapy has changed the clinical treatment of non‐small cell lung cancer (NSCLC) in the past few years. The success of PD‐1 blockade therapy has been attributed to high tumor mutation burden and high immunogenicity of lung cancer cells. To further improve the efficacy of NSCLC immunotherapy and overcome the resistance of lung cancer cells to immune checkpoint blockade, new approaches that enhance the active immune response, such as neoantigen vaccines and cellular‐based therapies, are urgently required. Neoantigens are considered ideal targets for cancer immunotherapy because of their high immunogenicity and specificity. In this mini review, we first discuss the current advances in neoantigen vaccines for treating cancers and then review the results of preclinical studies and early‐phase human clinical trials of neoantigen‐based therapies for NSCLC. Finally, we focus on the identification of neoantigens in patients with NSCLC and review the candidate mutations reported by recent studies and our investigations. The review concludes that, in addition to immune checkpoint blockade, approaches targeting neoantigens are promising for improving the efficacy of NSCLC immunotherapy.

Abstract Background Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). Methods We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. Results We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. Conclusions Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

Background and objective The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. Methods We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. Results All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. Conclusion Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Abstract Background Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients. Methods This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2/m2] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. Results A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (

AIM: To investigate whether Wild Field Imaging System (WFIS SW-8000), 25G endoilluminator, and intraoperative optical coherence tomography (iOCT) can perform real-time screening and diagnosing in patients with suspicious diabetic retinopathy (DR) during phacoemulsification, especially in cases of white cataract. METHODS: A cross-sectional study was carried out. A total of 204 dense diabetic cataractous eyes of 204 patients with suspected DR treated from April 2020 to March 2021 were included. Phacoemulsification combined with intraocular lens implantation was performed. Following the removal of the lens opacity, the 25G endo-illuminator, fundus photography, and iOCT were performed successively. Optical coherence tomography (OCT) and/or fundus fluorescein angiography (FFA) were used to verify the fundus findings postoperatively. Intraoperative and postoperative results were compared to verify the accuracy of intraoperative diagnosis in each group. RESULTS: Intraoperative and postoperative examinations revealed 58 and 62 eyes with DR, respectively (positive rate, 28.43% and 30.39%, respectively). During the phacoemulsification, WFIS SW-8000 detected 44 eyes with DR (the detection rate, 70.97%); 25G endo-illuminator found 56 eyes with DR (the detection rate, 90.32%); iOCT found 46 eyes with DR (the detection rate, 74.19%); and 58 eyes with DR were found by combining the three methods (the detection rate, 93.55%). There were statistically significant differences in the diagnostic sensitivity for DR among the methods (χ2=16.36, P=0.001). CONCLUSION: WFIS SW-8000, 25G endo-illuminator, iOCT, and especially their combination can be used to inspect the fundus and detect DR intraoperatively; they are helpful for the timely diagnosis and treatment of DR in patients with dense cataract.

BackgroundThe worldwide spread of monkeypox (mpox) has witnessed a significant increase, particularly in nonendemic countries. ObjectiveWe aimed to investigate the changing clinical symptoms associated with mpox from 1970 to 2023 and explore their interrelations. MethodsIn this systematic review and meta-analysis, 3 electronic databases were searched for English peer-reviewed studies conducted from January 1970 to April 2023 that reported any symptoms among confirmed mpox cases. We categorized the mpox epidemics into 3 periods: 1970-2002 (period 1, within the African region), 2003-2021(period 2, epidemics outside Africa), and 2022-2023 (period 3, worldwide outbreak). Following PRISMA guidelines, a meta-analysis was performed to estimate the pooled prevalence for each symptom. The correlation among symptoms was analyzed and visualized using network analysis. ResultsThe meta-analysis included 61 studies that reported 21 symptoms in 720 patients from period 1, 39 symptoms in 1756 patients from period 2, and 37 symptoms in 12,277 patients from period 3. The most common symptom among patients from all 3 periods was rash (period 1: 92.6%, 95% CI 78.2%-100%; period 2: 100%, 95% CI 99.9%-100%; and period 3: 94.8%, 95% CI 90.9%-98.8%), followed by lymphadenopathy (period 1: 59.8%, 95% CI 50.3%-69.2%; period 2: 74.1%, 95% CI 64.2%-84.1%; and period 3: 61.1%, 95% CI 54.2%-68.1%). Fever (99%, 95% CI 97%-100%), enlarged lymph nodes (80.5%, 95% CI 75.4%-85.0%), and headache (69.1%, 95% CI 4%-100%) were the main symptoms in period 1, with a significant decrease in period 3: 37.9%, 31.2%, and 28.7%, respectively. Chills/rigors (73.3%, 95% CI 60.9%-85.7%), fatigue (68.2%, 95% CI 51.6%-84.8%), and dysphagia/swallowing difficulty (61.2%, 95% CI 10.5%-100%) emerged as primary new symptoms in period 2 and decreased significantly in period 3. Most other symptoms remained unchanged or decreased in period 3 compared to the former 2 periods. Nausea/vomiting had the highest degree of correlation (with 13 symptoms) and was highly positively correlated with lymphadenopathy (r=0.908) and conjunctivitis (r=0.900) in period 2. In contrast, rash and headache were 2 symptoms with the highest degree of correlation (with 21 and 21 symptoms, respectively) in period 3 and were highly positively correlated with fever (r=0.918 and 0.789, respectively). ConclusionsThe manifestation of symptoms in patients with mpox has become more diverse, leading to an increase in their correlation. Although the prevalence of rash remains steady, other symptoms have decreased. It is necessary to surveil the evolving nature of mpox and the consequential changes in clinical characteristics. Epidemic countries may shift their focus on the potential association among symptoms and the high synergy risk. Trial RegistrationPROSPERO Registration: CRD42023403282; http://tinyurl.com/yruuas5n

BackgroundThe World Health Organization emphasizes the importance of completely voluntary blood donation to maintain safe and sustainable blood supplies. However, the benefits of blood donation for donors, such as reducing the risk of disease, remain a topic of debate due to the existence of the healthy donor effect (HDE). This effect arises because of inherent health differences between blood donors and the general population, and it is also considered a methodological issue. ObjectiveThis study aims to generate a more detailed health profile of blood donors from a donor cohort study to mitigate and quantify the HDE and properly interpret the association between blood donation and disease outcomes among blood donors. MethodsA retrospective cohort study was conducted between January 2012 and December 2018 among donors before their first donation. One-to-one propensity score matching was conducted through a random selection of individuals without any history of blood donation, as reported from their electronic health records. We conducted a Poisson regression between blood donors and non–blood donors before the first donation to estimate the adjusted incidence rate ratio (AIRR) of selected blood donation–related diseases, as defined by 13 categories of International Classification of Diseases, Tenth Revision (ICD-10) codes. ResultsOf the 0.6 million blood donors, 15,115 had an inpatient record before their first donation, whereas 17,356 non–blood donors had an inpatient record. For the comparison between blood donors and the matched non–blood donors, the HDE (the disease incidence rate ratio between non–blood donors and blood donors) was an AIRR of 1.152 (95% CI 1.127-1.178; P

IntroductionThe metro has emerged as a major mode of transportation. A significant number of commuters and staff in the metro system are exposed to air pollutants because of its shielded environment, and substantial health damage requires quantitative assessment. Previous studies have focused on comparing the health impacts among different transportation modes, overlooking the specific population characteristics and pollutant distribution in metro systems.MethodsTo make improvements, this study implements field monitoring of the metro's air environment utilizing specialized instruments and develops a health damage assessment model. The model quantifies health damage of two main groups (commuters and staff) in metro systems at three different areas (station halls, platforms, and metro cabins) due to particulate matter 10 and benzene series pollution.ConclusionA case study of Nanjing Metro Line 3 was conducted to demonstrate the applicability of the model. Health damage at different metro stations was analyzed, and the health damage of commuters and staff was assessed and compared. This study contributes to enhancing research on health damage in the metro systems by providing a reference for mitigation measures and guiding health subsidy policies.

Metastatic carcinoma of the paranasal sinuses in lung cancer is an extremely uncommon condition. We report here a 57-year-old female patient with epidermal growth factor receptor (EGFR)-positive stage IV non-small cell lung cancer (NSCLC) with multiple bone metastases. After resistance to second- and third-generation EGFR-tyrosine kinase inhibitors (TKIs), the patient presented with headache accompanied by progressively enlarging lesions of the nasal cavity on CT scan. Further endoscopic sinus neoplasmectomy confirmed sinus metastasis of lung adenocarcinoma. Although subsequent chemotherapy and immunotherapy were both administered, the disease continued to progress, and the patient passed away 21 months after diagnosis. Combined with real-time dynamic next-generation sequencing (NGS) during the different generations of EGFR-TKI treatments and dynamic tumour microenvironment analysis, we discussed the clinical manifestations of sinus metastasis and the molecular biology and tumour immune microenvironment changes after resistance to the second-and third- generation of EGFR-TKI therapy.

Introduction We explored the relationship and the predictive value of serum fibroblast growth factor 21 (FGF21) with all-cause mortality, major adverse cardiovascular events (MACEs) and pneumonia in hemodialysis (HD) patients.Methods A total of 388 Chinese HD patients from two HD centers were finally enrolled in this prospective cohort study (registration number: ChiCTR 1900028249) between January 2018 and December 2018. Serum FGF21 was detected. Patients were followed up with a median period of 47 months to record the MACEs and pneumonia until death or 31 December 2022.Results The incidence of all-cause mortality, MACEs and pneumonia in HD patients were 20.6%, 29.6%, and 34.8%, respectively. The optimal cutoffs for FGF21 to predict all-cause mortality, MACEs and pneumonia were 437.57 pg/mL, 216.99 pg/mL and 112.79 pg/mL. Multivariate Cox regression analyses showed that FGF21, as a categorical variable, was an independent predictor for all-cause mortality, MACEs and pneumonia (HR, 3.357, 95% CI, 2.128–5.295, p

Background & Aims: Globally, one-third of individuals infected with HBV live in China. Eliminating HBV in China would therefore be paramount in achieving the World Health Organization’s (WHO’s) targets of viral hepatitis elimination as a worldwide public health threat. Methods: We constructed a dynamic HBV transmission model in China, structured by age and sex. We calibrated the model by HBsAg prevalence, acute HBV incidence, and nationally reported HBV-related cancer mortality. We investigated seven intervention scenarios (A–G) based on assumptions in diagnostic, linkage-to-care, and treatment coverages in achieving the WHO’s HBV elimination goals. Results: With the status quo, HBsAg prevalence among children 1–4 years would reduce to 0.09% (95% CI 0.09–0.10%) by 2025; acute HBV incidence would drop to

Recently, the rapidity-odd directed flow (v1) of produced hadrons (K−, ϕ, p¯, Λ¯, Ξ¯+, Ω−, and Ω¯+) has been studied. Several combinations of these produced hadrons, with very small mass differences but differences in the net electric charge (Δq) and net strangeness (ΔS) on the two sides, have been considered. A difference in v1 between the two sides of these combinations (Δv1) has been proposed as a consequence of the electromagnetic field produced in relativistic heavy-ion collisions, especially if Δv1 increases with Δq. Our study is performed to understand the effect of the coalescence sum rule (CSR) on Δv1. We point out that the CSR leads to Δv1=cqΔq+cSΔS, where the coefficients cq and cS reflect the Δv1 of produced quarks. Equivalently, one can write Δv1=cqΔq+cBΔB, involving the difference in the net baryon number ΔB, where the CSR gives cB=−3cS. We then propose two methods to extract the coefficients for the Δq and ΔS dependences of Δv1.

Objectives: Environmental, socioeconomic, and genetic factors all are associated with respiratory diseases. We aimed to investigate the association between the ABO blood group and the susceptibility to respiratory diseases. Methods: We constructed a retrospective cohort study of blood donors in Shaanxi, China between January 1, 2012, and December 31, 2018, to investigate the impacts of the ABO blood group on the risk of hospitalization due to respiratory diseases. Results: Of 1,686,263 enrolled participants (680,788 females), 26,597 were admitted to the hospital for respiratory diseases. Compared with blood group O, blood groups A, B, and AB all demonstrated a higher risk for diseases of the upper respiratory tract (International Classification of Diseases, Tenth Revision: J30–J39) (ARR (Adjusted relative risk) 1.139, 95% confidence interval [1.106–1.225]; 1.095 [1.019–1.177]; 1.178 [1.067–1.30], respectively). Conversely, blood group A was found to have a lower risk (0.86 [0.747–0.991]) for influenza (J09–J11) and blood group B had a lower risk for pneumonia (J12–J18) (0.911 [0.851–0.976]) than blood group O. The duration of hospitalization was significantly different across the blood groups in J09–J11 and J30–J39 (P

Here the authors show that a RalGAPα1-RalA signal nexus regulates calcium homeostasis in cardiomyocytes via the calcium pump SERCA2a, which plays a protective role to maintain cardiac function under pressure overload conditions.

Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.

Measurement(s) Catheter Device Technology Type(s) Annotation Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15113043

Comprehensive Summary: Unsymmetric sulfides and selenides have great applications in the pharmaceutical field. Herein, we describe the reductive coupling reaction of xanthate esters with sulfur‐containing and selenium‐containing compounds (thio(seleno)sulfonates and disulfides(selenides)) under the nickel‐catalyzed condition. It provides a mild and effective method for the synthesis of unsymmetric sulfides and selenides which has the advantages of mild reaction conditions, high yields and a wide range of substrates. [ABSTRACT FROM AUTHOR]

Abstract Background May–Thurner syndrome is an anatomical condition characterized by compression of the left common iliac vein by the right common iliac artery, causing venous outflow obstruction. It is an uncommon cause of deep vein thrombosis and is more prevalent among women. This paper highlights the importance of considering May–Thurner syndrome in young males without risk factors presenting with left lower limb pain, as endovascular treatment may be required. Case presentation A 23 year-old Caucasian male presented with a 1-week history of left lower limb pain, edema, and pallor. He was found to have an unprovoked deep vein thrombosis on Doppler ultrasound involving the left fibular, soleus, gastrocnemius, popliteal, femoral, common femoral, and external iliac veins. A heparin infusion was commenced as the initial treatment for deep vein thrombosis. Further investigation with computer tomography pulmonary angiogram and computer tomography venography of the abdomen and pelvis showed bilateral pulmonary emboli and left common iliac vein compression with left common, internal, and external iliac vein thrombosis. He was diagnosed with May–Thurner syndrome despite having no risk factors. A retrievable Cook Celect Platinum inferior vena cava filter was placed, and thrombus of the left common femoral, external, and common iliac veins was treated successfully with AngioJet thrombectomy, thrombolysis using 200,000 units of urokinase, angioplasty and stenting using two Cook Zilver Vena venous self-expanding stents. Therapeutic enoxaparin was commenced on discharge. His filter was removed after 10 weeks. Hematological follow-up 4 months later showed an overall negative thrombophilia screen, and anticoagulation was switched to apixaban. He has had no recurrent thrombosis. Conclusions Clinicians should have a low threshold to investigate for May-Thurner syndrome in patients with left lower limb venous thrombotic events regardless of risk factors, as endovascular treatment may be required to minimize the long-term sequelae of deep vein thrombosis. Duplex ultrasound can be used initially for diagnosis, and computer tomography venography used subsequently if the common iliac vein is not visualized on ultrasound. Endovascular treatment is preferred over anticoagulation alone, especially in otherwise fit patients presenting early, the aim being to reduce the chances of chronic venous hypertension in the lower limb.

ObjectiveChemotherapy-related brain impairments and changes can occur in patients with lung cancer after platinum chemotherapy and have a substantial impact on survivors’ quality of life. Therefore, it is necessary to understand the brain neuropathological alterations and response mechanisms to provide a theoretical basis for rehabilitation strategies. This study aimed to investigate the related brain morphological changes and clarified their correlation with clinical and pathological indicators in patients with lung cancer after platinum chemotherapy.MethodsOverall, 28 patients with chemotherapy, 56 patients without chemotherapy, and 41 healthy controls were categorized in three groups, matched for age, sex, and years of education, and included in the cross-sectional comparison of brain volume and cortical thickness. 14 matched patients before and after chemotherapy were subjected to paired comparison for longitudinal observation of brain morphological changes. Three-dimensional T1-weighted images were acquired from all participants, and quantitative parameters were calculated using the formula of the change from baseline. Correlation analysis was performed to evaluate the relationship between abnormal morphological indices and clinical information of patients.ResultsBrain regions with volume differences among the three groups were mainly distributed in frontal lobe and limbic cortex. Additionally, significant differences in cerebrospinal fluid were observed in most ventricles, and the main brain regions with cortical thickness differences were the gyrus rectus and medial frontal cortex of the frontal lobe, transverse temporal gyrus of the temporal lobe, insular cortex, anterior insula, and posterior insula of the insular cortex. According to the paired comparison, decreased brain volumes in the patients after chemotherapy appeared in some regions of the frontal, parietal, temporal, and occipital lobes; limbic cortex; insular cortex; and lobules VI-X and decreased cortical thickness in the patients after chemotherapy was found in the frontal, temporal, limbic, and insular cortexes. In the correlation analysis, only the differentiation degree of the tumor and duration after chemotherapy were significantly correlated with imaging indices in the abnormal brain regions.ConclusionsOur findings illustrate the platinum-related brain reactivity morphological alterations which provide more insights into the neuropathological mechanisms of patients with lung cancer after platinum chemotherapy and empirical support for the details of brain injury related to cancer and chemotherapy.

Small-scale fisheries (SSFs) in China have made incalculable contributions to the supply of aquatic products, employment, and social stability. Despite their importance, aspects such as the complexity, dynamicity, and vulnerability of SSFs are yet to receive sufficient attention either from the Chinese government or from society. Here we help to address the lack of recognition of SSFs by examining their characteristics and possible management solutions. We selected Shengsi County, a community with traditional fishing activities, in Zhejiang Province as a case study to review and examine the SSFs’ characteristics and policies. We aimed to explore the improvement strategies for Chinese SSF management by using data from the open-access government databases, a series of questionnaire surveys and semi-structured interviews, and a collection of national and local SSF-related legislative and policy documents. Here we summarized the physical characteristics of the small-scale fishing vessels and the socioeconomic aspects of SSFs in Shengsi County. Our findings indicate that unprecedented new institutional arrangements for SSFs have been developed in recent years at the national level, and some relevant policies of SSFs also exist at the local level. However, there are still gaps: The concept of SSFs and the goal of their management have not been developed either at the national or local levels; monitoring systems have not yet been established for collecting SSF-related data; fishers engaged in SSFs are still not well organized; cooperation and coordination between different government departments with management authority over SSFs are insufficient; the local government’s response to the central government’s initiatives was slow. Our findings show that the Chinese government could improve SSF management by adopting on an ongoing basis the following suggestions: (1) better define SSFs and set management goals according to their characteristics; (2) develop a monitoring system for SSFs’ data and information collection and promote multidisciplinary research on SSFs; (3) establish SSFs’ cooperatives as soon as possible; and (4) develop coordination and cooperation mechanisms among government departments. This research can provide a reference for the Chinese government to understand SSFs better and contribute to the implementation and improvement of SSFs’ differentiated management in China.

Molecular mechanisms linking myocardial insulin resistance to diabetic cardiomyopathy are incompletely understood. Here the authors show that myocardial insulin resistance impairs a PKB-SPEG-SERCA2a signaling axis, which contributes to the development of diabetic cardiomyopathy.

PurposeThe Shaanxi Blood Donor Cohort was set up to investigate the impact of blood donation on the health of donors compared with non-blood donors. The specific aims of the study include (1) identifying the geographical and temporal trends of incidence for diseases in both blood donors and non-blood donors; (2) assessing the impact of environmental exposures, lifestyle, body mass index (BMI) and blood type on disease burdens, stratified between blood donors and non-blood donors; and (3) among blood donors, investigating if regular blood donation has a positive impact on donors’ health profiles, based on a cohort with a mixed retrospective and prospective study design.ParticipantsA total of 3.4 million adults, with an equal number and identical demographic characteristics (year of birth, sex and location of residence) of blood donors and non-blood donors, were enrolled on 2012. The one-to-one matching was conducted through a repeated random selection of individuals without any history of blood donation from the Shaanxi Electronic Health Records. The cohort has been so far followed up to the end of 2018, summing to nearly 24 million years of follow-up. The cohort will be followed up prospectively every 3 years until 2030.Findings to DateOf the 1.7 million blood donors, 418,312 (24.5%) and 332,569 (19.5%) individuals were outpatients and inpatients, accounting for 1,640,483(96.2%) outpatient and 496,061 (29.1%) inpatient visits. Of the same number of non-blood donors, 407,798 (23.9%) and 346,097 (20.3%) individuals were hospital outpatients and inpatients, accounting for 1,655,725 (97.1%) outpatient and 562,337 (33.0%) inpatient visits. The number of outpatient and inpatient visits by non-blood donors was 0.9 and 3.9% higher than those of the blood donors (p < 0.01). Blood donors demonstrate significantly fewer inpatients visits than non-blood donors for major chronic disease categories (p < 0.01).Future PlansWe are currently exploring the long term benefits of blood donation on major chronic disease categories and multimorbidities in this large population cohort. The study results are adjusted by the “healthy donor effect.” This cohort study will continue until 2030.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in neurons in the central nervous system. It has been documented that HCN channels regulate the intrinsic excitability of pyramidal cells in the medial prefrontal cortex (mPFC) of rodents. Here, we report that HCN channels limited GABAergic transmission onto pyramidal cells in rat mPFC. The pharmacological blockade of HCN channels resulted in a significant increase in the frequency of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in mPFC pyramidal cells, whereas potentiation of HCN channels reversely decreases the frequency of mIPSCs. Furthermore, such facilitation effect on mIPSC frequency required presynaptic Ca2+ influx. Immunofluorescence staining showed that HCN channels expressed in presynaptic GABAergic terminals, as well as in both soma and neurite of parvalbumin-expressing (PV-expressing) basket cells in mPFC. The present results indicate that HCN channels in GABAergic interneurons, most likely PV-expressing basket cells, constrain inhibitory control over layer 5–6 pyramidal cells by restricting presynaptic Ca2+ entry.

Residential districts, the primary locations for older adults, struggle to satisfy the needs of the rising older population due to ageing infrastructure, etc. China has begun to focus on this issue through the popularization of approaches such as active ageing theory (AAT), and has implemented ageing suitability renovations. Meanwhile, recent evaluation models failed to validate their logic and standardization. The current evaluation models prioritize the indoor environment above the external environment. Therefore, this study attempts to provide a comprehensive evaluation model of the ageing suitability of residential districts. First, 23 indicators of ageing suitability were identified by a systematic literature review and expert interviews; next, the indicators were categorized using the active ageing theory. Second, the grey correlation analysis approach was used to calculate the weights of evaluation indicators, and the existing evaluation criteria were incorporated to formulate the evaluation criteria for the project. Eventually, the evaluation model was constructed. Finally, the feasibility of the model was validated by a case study. The findings of this study can help provide directions for the future renovation of old residential districts (for example, the activity area should be over 200 m2) and the construction of suitable houses for older adults, such as the installation of a continuous handrail, to alleviate the increasingly grave problem of ageing and promote the development of the pension industry.

Purpose. To determine the incidence of anterior chamber (AC) instability during phacoemulsification (phaco) combined with intraocular lens implantation and investigate its effect on intraocular tissues. Methods. Among the 248 enrolled eyes, 121 and 127 eyes were categorized into the irrigation and nonirrigation groups, respectively, depending on the use of a self-made anterior chamber maintainer (ACM) during phaco. AC stability was evaluated using operating microscopy and intraoperative optical coherence tomography (iOCT). Slit-lamp examination of AC flare and cells was performed 1 day postoperatively. Corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), central corneal thickness (CCT), posterior vitreous detachment (PVD), and central foveal thickness (CFT) were evaluated preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results. There was good consistency in AC stability evaluation between operating microscopy and iOCT. The incidence of AC instability was significantly different between groups after the phaco and irrigation/aspiration tips were withdrawn from the AC P0.05. At 1 month and 3 months postoperatively, PVD occurred in 8 (16.3%) and 14 (28.6%) eyes and in 22 (40.7%) and 37 (68.5%) eyes in the irrigation and nonirrigation groups, respectively (P = 0.006 and P