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Abstract In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.

Abstract Numerous geothermal systems are hosted by extensional rifts that transect the Himalayas and Lhasa block in the Himalayan–Tibetan orogen. However, the relationships between hydrogeological processes and geothermal fluid circulation in different tectonic units remain unclear. Here, we report an integrated dataset of chemical and isotopic compositions (including major and trace elements, δD, δ18O, and 87Sr/86Sr) of thermal spring water from the Tingri-Tangra Yumco rift to assess their origins and circulation processes. δ18O (− 21.3 to − 17.0‰) and δD (− 166 to − 135‰) values of thermal springs indicate dominant recharge of meteoric waters from areas with elevation of > 6000 m and minor addition of magmatic fluids. Meteoric water could infiltrate to depths of about 1700–2900 m along the faults, whereby it is influenced by geothermal gradient and/or conductive heat transfer of magmatic fluids. The thermal spring waters are mainly Na-HCO3 type and are controlled by dissolution of silicate and carbonate minerals and mixing with deep fluids. The results of chemical and multicomponent geothermometers indicate reservoir temperatures of 115 − 195 ℃, corresponding to a convection heat flux of 3.96 × 105 J/s to 1.78 × 107 J/s from geothermal systems, which are comparable to that of the low-enthalpy geothermal systems in southern Italy. Geochemical modeling is conducted to assess the water–mineral equilibria in the reservoir. Trace elements and 87Sr/86Sr data suggest spatially variable controlling factors for the rift-related geothermal systems: (1) interaction with granitoid and carbonate in the Himalayas; (2) cold groundwater mixing with that leaching from granite and volcanic rocks in the Lhasa block; (3) the input of vapors from magmatic degassing. The geochemistry of thermal springs associated with extensional rift is largely induced by the interaction between fluid and different reservoir rocks in the Himalayas and Lhasa block. Based on these findings, a genetic model is proposed for exploration and development of geothermal resources in the Tingri-Tangra Yumco rift.

Abstract Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge. Here, we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs. First, two PC markers, Shox2 and Hcn4, were selected to establish Shox2:EGFP; Hcn4:mCherry mouse PSC reporter line. Then, by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation, we designed the FSK method that increased the yield of SHOX2+; HCN4+ cells with typical PC characteristics, which was 12 and 42 folds higher than that of the embryoid body (EB) and the monolayer M10 methods respectively. In addition, the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing (scRNA-seq), which resembled in vivo PCs development, and ZFP503 was verified as a key regulator of cardiac PCs differentiation. These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology, help with the understanding of PCs (patho)physiology, and benefit drug discovery for PC-related diseases as well.

Earthquakes are major catastrophes that cause great life and economic losses to human society and environment. This paper reviews and synthesizes relevant studies, drawing from a systematic examination of 4229 articles from the Web of Science core collection (1982–2023). Employing the CiteSpace visualization and analysis tool, current research and emerging trends in seismic risk assessment are discussed and analyzed. This paper provides a holistic overview of principal contributions, knowledge sources, interdisciplinary characteristics, and principal research topics in this field. Additionally, we propose key technologies that are in urgent need of enhancement, including data availability, quantity and quality of data, interpretability of machine learning models, performance improvement of machine learning methods and application of foundation models, as well as real-time risk assessment techniques. These insights support both theoretical understanding and practical applications of seismic risk assessment and damage analysis.

Evaluating the recognizability of street built environments provides crucial support for urban planning, security monitoring and navigation. Although street view images (SVIs) are widely used in urban studies, it overlooks the interconnection among different locations, which can also affect perceptions about environmental recognizability. To address this issue, this study proposes a deep learning-based model called RB-Node, which comprehensively integrates spatial structural features in a road network view and visual features from SVIs, achieving 82.56% accuracy. It appears that image information from visual features dominates environmental recognizability. Additionally, structural information contributes significantly to the accurate classification of nodes and waterfront promenade areas. Moreover, scene-text information, a subset of visual features, helps classify commercial and historical areas. Furthermore, 1056 samples were collected through an eye-tracking experiment to validate the recognizability evaluation results, as well as compare the decision-making process between humans and RB-Node. According to the results, RB-Node behaviour and human observed behavior follow similar patterns, although human perceptions tend to be more holistic than RB-Node's. This study contributes to a better understanding of environmental recognizability and provides targeted recommendations for urban renewal.

Background: Following recent research advancements, an increasing level of evidence had been published to indicate that celastrol exerted a therapeutic effect on a range of nervous system diseases. This study therefore aimed to investigate the potential involvement of celastrol on ferroptosis and the blood-brain barrier disruption in intracerebral haemorrhage. Methods: We established a rat intracerebral haemorrhage and adrenal pheochromocytoma cell (PC12) OxyHb models using an ACSL4 overexpression vector. Ferroptosis-related indices were assessed using corresponding assay kits, and immunofluorescence and flow cytometry were used to measure reactive oxygen species (ROS) levels. Additionally, quantitative PCR (qPCR) and western blot analyses were conducted to evaluate the expression of key proteins and elucidate the role of celastrol in intracerebral haemorrhage (ICH). Results: Celastrol significantly improved neurological function scores, blood-brain barrier integrity, and brain water content in rats with ICH. Moreover, subsequent analysis of ferroptosis-related markers, such as Fe2+, ROS, MDA, and SOD, suggested that celastrol exerted a protective effect against the oxidative damage induced by ferroptosis in ICH rats and cells. Furthermore, Western blotting indicated that celastrol attenuated ferroptosis by modulating the expression levels of key proteins, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and anti-transferrin receptor 1 (TFR1) both in vitro and in vivo. ACSL4 overexpression attenuated the neuroprotective effects of celastrol on ICH in vitro. Molecular docking analysis revealed that celastrol interacted with ACSL4 via the GLU107, GLN109, ASN111, and LYS357 binding sites. Conclusions: Celastrol exerted antioxidant properties and aids in neurological recovery after stroke by suppressing ACSL4 expression during ferroptosis. As such, this drug represented a promising pharmaceutical candidate for the treatment of ICH.

Loess has unique physical, hydrodynamic and mechanical properties, which are influenced by both internal and external geological processes, as well as human engineering activities. Consequently, surface disasters are especially prevalent in the Loess region of China. The study area is situated in the middle part of Lüliang Mountain in the middle part of the Loess Plateau, which is characterised by a typical loess landform with a complex system of gullies and hill ridges. According to current theory, the cracking boundary of the goaf profile is a straight line. However, these surface disasters are actually caused by the shear action of the deep rock layer and the original vertical joint structure of the loess. By analysing the cracking process of the ‘Goaf-Overburden-Loess’ section in the study area, it can be found that the boundary of the movement basin section presents a broken line shape, which has important implications for the accurate estimation of the area affected by loess-type surface subsidence.

The experiment sought to determine the effects of substituting Flammulina velutipes residue (FVR) for corn on growth performance, serum biochemical parameters, slaughter performance and caecum microbiota of geese. One hundred and ninety-two 35old Hordobagy geese were used in this experiment, and they were divided into four groups and fed with various diets for 28 d. The geese in the control group were fed with a basal diet. The other groups substituted 12%, 24% and 32% FVR for corn in their diets, respectively. There was no significant difference in the feed/gain ratio between the addition of 12% and 24% FVR to the diet, however, these additions considerably raised final body weight, average daily feed intake, and average daily growth (p

ObjectiveStroke risk factors often exert long-term effects, and Mendelian randomization (MR) offers significant advantages over traditional observational studies in evaluating the causal impact of these factors on stroke. This study aims to consolidate and evaluate the relationships between potential causal factors and stroke risk, drawing upon existing MR research.MethodsA comprehensive search for MR studies related to stroke was conducted up to August 2023 using databases such as PubMed, Web of Science, Embase, and Scopus. This meta-analysis examines the relationships between potential causative factors and stroke risk. Both random-effects and fixed-effects models were utilized to compile the dominance ratios of various causative elements linked to stroke. The reliability of the included studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology incorporating Mendelian Randomization (STROBE-MR) guidelines.ResultsThe analysis identified several risk factors for stroke, including obesity, hypertension, low-density lipoprotein cholesterol (LDL-C), chronic kidney disease (CKD), and smoking. Protective factors included high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), and educational attainment. Subgroup analysis revealed that type 2 diabetes mellitus (T2DM), diastolic blood pressure (DBP) are risk factors for ischemic stroke (IS).ConclusionThis study confirms that variables such as obesity, hypertension, elevated LDL-C levels, CKD, and smoking are significantly linked to the development of stroke. Our findings provide new insights into genetic susceptibility and potential biological pathways involved in stroke development.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024503049.

There exist some problems for acoustically excited super low frequency(SLF) antennas, such as low transmission power and low received signal-to-noise ratio. In addition, it is difficult to design a narrow-band filter in traditional binary frequency-shift keying(2FSK) non-coherent demodulation. Therefore, a 2FSK weak signal demodulation method based on a Duffing chaotic oscillator was proposed. Because the Duffing oscillator itself was sensitive to the phase, a phase synchronization method of “coarse synchronization + fine synchronization” was designed. The coarse synchronization was accomplished through the short-time Fourier transform, while the fine synchronization was achieved through the Duffing chaotic oscillator. Then, the properties of the chaotic oscillator, such as being sensitive to the same-frequency periodic signal and being immune to noise signals, were utilized, and the signal passed through two Duffing oscillators in parallel, with the built-in signal frequency of the two being consistent with the two carrier frequencies. At a certain moment when one system must be in the large-scale periodic state and the other in the chaotic state, the two systems could be discriminated to realize signal demodulation. The simulation results show that the proposed Duffing oscillator demodulation algorithm outperforms the non-coherent and coherent demodulation algorithms by 5 dB and 4 dB in bit error rate, respectively.

Autoimmune encephalitis is complex and gradually being recognized. Anti-N-methyl-D-aspartate Receptor (Anti-NMDAR) encephalitis was the most well-known and its unique electroencephalography (EEG) pattern is extreme delta brush (EDB). Anti-Yo encephalitits is far less than common anti-NMDAR encephalitis (anti-NMDARE). A 78-year-old male presented with progressive apathy, hypotension, unsteady gait, and depressed consciousness. EEG revealed an EDB pattern while the serum test was positive for anti-Yo antibodies. The patient then received 10 rounds of plasma exchange, and his blood pressure stability improved. Consequently, urine cytology and abdominal computed tomography revealed atypical cells and linear enhancement in the bladder dome, respectively. However, instead of further pathological confirmation and treatment, the patient’s family requested hospice care. As a result, the patient died of desaturation 7 days later after the withdrawal of ventilatory support. First recognized in 2012, EDB is believed to be specific to NMDARE. However, to date, EDB has not been well described, and no description is available regarding its reactivity. To our knowledge, this is the first case of EDB with anti-Yo encephalitis. Similar to the cases of EDB with anti-NMDARE, our patient did not have satisfied prognosis despite no further investigation and treatment of the possible underlying malignancy. As the prevalence and underlying mechanism of this EEG pattern are unclear, further studies are warranted to identify the potentially similar mechanisms and correlation between anti-NMDAR and anti-Yo encephalitis.

Abstract Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV‐associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Abstract Background Depression represents a frequent mental health challenge in individuals with fractures, negatively impacting their recuperation and overall well-being. The purpose of this research was to formulate and corroborate a prognostic framework for pinpointing depression risk among fracture sufferers by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020 and a separate hospital-based group. Methods We analyzed records from 1,748 individuals with fractures documented in the NHANES database spanning 2005 to 2020, of which 362 were diagnosed with depression, as indicated by a Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher. An additional validation group comprised 360 fracture patients sourced from a medical center. Considered variables for prediction encompassed demographic details, lifestyle habits, past medical conditions, and laboratory results. The method of least absolute shrinkage and selection operator (LASSO) regression facilitated the narrowing down of variables, while multivariate logistic regression was employed to pinpoint significant predictors. To assist in prediction, a nomogram was designed and subsequently validated. Results Five independent predictors were identified: drinking, insomnia, poverty-to-income ratio, education level, and white blood cell count. The nomogram showed good discrimination in the NHANES cohorts (training area under the curve (AUC) 0.734, validation AUC 0.740) and hospital-based external validation (AUC 0.711). Calibration curves and decision analysis supported its predictive accuracy and clinical value. Conclusion The constructed nomogram offers a precise and clinically relevant instrument for forecasting depression risk in patients with fractures, facilitating the early detection of individuals at high risk and enabling prompt intervention.

Abstract Background Although the Healthy Eating Index (HEI) is widely recommended to reduce the risk of cardiovascular disease and all-cause death, there are significant differences in physiological and nutritional factors between the sexes. The potential impact of sex on adult dietary health is still poorly understood. The study was designed to assess whether the health benefits of diet differed by sex. Methods In a prospective study of 39,567 U.S. adults (51.2% female, age 46.8 ± 17.6 years), we examined sex-specific, multivariable-adjusted associations of HEI with all-cause mortality and cardiovascular disease mortality. Restricted cubic splines (RCS), subgroup analysis, propensity score matching (PSM), random forest feature importance, and sensitivity analysis were also used. Results During 328,403 person-years of follow-up, a total of 4754 all-cause deaths were recorded, including 1481 cardiovascular deaths. Compared to the lowest quartile of HEI, the all-cause mortality rate of females and males in the highest quartile array decreased by 34% (HR 0.66 [95% CI 0.55–0.8]) and 15% (HR 0.85 [95% CI 0.73–0.99]), respectively. The restricted cubic spline showed a linear inverse association between baseline HEI and all-cause mortality and CVD mortality, with similar sex-specific results. Similarly, component scores were sex-specific for mortality risk, with females benefiting more from diet. The benefits of dairy products, vegetables, and sodium scores on the risk of all-cause death were higher in males and females. However, the benefits of vegetable, sodium, and fatty acid scores on the risk of cardiovascular death were different. Conclusions In the adult population of the U.S., there are more opportunities for females to reduce the risk of all-cause mortality and cardiovascular mortality from the same dose of healthy dietary intake than males. These findings could reduce the risk of death by motivating the population, especially females, to consume healthy dietary components, especially vegetables and dairy products.

Objective To evaluate the effect of chronic disease health management on disease activity and renal injury in patients with lupus nephritis (LN). Methods A total of 97 LN patients diagnosed with lupus nephritis were randomizedly assigned to into two groups of chronic disease health management (n=49) and conventional management (n=48). and followed up for a median of 6 months. The disease activity index (SLEDAI), and blood and urinarye parameters and medicine compliance and living quality-of-life (SF-36) and trust in doctor physician were recordedobserved in at Month 6.Results Patients who managed by of chronic disease health management had lower disease activity compared to conventional group (P

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). Methods This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants’ CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. Results During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32–1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). Conclusions An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

Abstract Background Bone loss of residual alveolar ridges is a great challenge in the field of dental implantology. Deproteinized bovine bone mineral (DBBM) is commonly used for bone regeneration, however, it is loose and difficult to handle in clinical practice. Hyaluronic acid (HA) shows viscoelasticity, permeability and excellent biocompatibility. The aim of this study is to evaluate whether high-molecular-weight (MW) HA combined with DBBM could promote new bone formation in rat calvarial critical size defects (CSDs). Materials and methods Rat calvarial CSDs (5 mm in diameter) were created. Rats (n = 45) were randomly divided into 3 groups: HA-DBBM compound grafting group, DBBM particles only grafting group and no graft group. Defect healing was assessed by hematoxylin-eosin staining and histomorphometry 2, 4 and 8 weeks postop, followed by Micro-CT scanning 8 weeks postop. Statistical analyses were performed by ANOVA followed by Tukey's post hoc test with P

Abstract Background Due to the unique working environment and nature of work in emergency departments, nurses are prone to experiencing compassion fatigue (CF), leading to job burnout and attrition. As more Generation Z (Gen Z) nurses enter the emergency department with distinct personality traits compared to previous generations, studying their experiences with CF will inform future management strategies. Methods The qualitative phenomenological research method was utilised to investigate CF among Gen Z emergency nurses at a hospital in Shanghai, China. Data were collected through face-to-face semi-structured interviews and analyzed using Colaizzi’s seven-step phenomenological analysis method. Study participants were purposively selected. Results Three main themes and nine sub-themes emerged from the study: secondary traumatic stress, including physiological symptoms, psychological symptoms, and behavioral changes; cumulative effects, including impaired empathy, interference with family life, and post-traumatic growth (PTG); coping strategies, including cognitive reconstruction, seeking support, and facilitating action. Conclusions The aim of this study is to investigate the experience of CF among Gen Z emergency nurses, providing managers with a reference for future management strategies. The significance of multi-dimensional support for Gen Z emergency nurses is underscored by our findings. Additionally, interventions that enhance resilience and competency can facilitate their psychological transformation after experiencing CF and promote accelerated personal growth.

Abstract Background Vascular invasion (VI) is closely related to the metastasis, recurrence, prognosis, and treatment of gastric cancer. Currently, predicting VI preoperatively using traditional clinical examinations alone remains challenging. This study aims to explore the value of radiomics analysis based on preoperative enhanced CT images in predicting VI in gastric cancer. Methods We retrospectively analyzed 194 patients with gastric adenocarcinoma who underwent enhanced CT examination. Based on pathology analysis, patients were divided into the VI group (n = 43) and the non-VI group (n = 151). Radiomics features were extracted from arterial phase (AP) and portal venous phase (PP) CT images. The radiomics score (Rad-score) was then calculated. Prediction models based on image features, clinical factors, and a combination of both were constructed. The diagnostic efficiency and clinical usefulness of the models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results The combined prediction model included the Rad-score of AP, the Rad-score of PP, Ki-67, and Lauren classification. In the training group, the area under the curve (AUC) of the combined prediction model was 0.83 (95% CI 0.76–0.89), with a sensitivity of 64.52% and a specificity of 92.45%. In the validation group, the AUC was 0.80 (95% CI 0.67–0.89), with a sensitivity of 66.67% and a specificity of 88.89%. DCA indicated that the combined prediction model might have a greater net clinical benefit than the clinical model alone. Conclusion The integrated models, incorporating enhanced CT radiomics features, Ki-67, and clinical factors, demonstrate significant predictive capability for VI. Moreover, the radiomics model has the potential to optimize personalized clinical treatment selection and patient prognosis assessment.

Abstract Background OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). Methods A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. Results The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P

Abstract Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Abstract The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Abstract Backgrounds To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. Methods We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25–65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. Results A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. Conclusions In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Background In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients’ tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy’s tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date. Methods A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival. Discussion This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy. Trial registration The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023.

Abstract There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p

Abstract As a new grinding and maintenance technology, rail belt grinding shows significant advantages in many applications. The dynamic characteristics of the rail belt grinding vehicle largely determines its grinding performance and service life. In order to explore the vibration control method of the rail grinding vehicle with abrasive belt, the vibration response changes in structural optimization and lightweight design are respectively analyzed through transient response and random vibration simulations in this paper. Firstly, the transient response simulation analysis of the rail grinding vehicle with abrasive belt is carried out under operating conditions and non-operating conditions. Secondly, the vibration control of the grinding vehicle is implemented by setting vibration isolation elements, optimizing the structure, and increasing damping. Thirdly, in order to further explore the dynamic characteristics of the rail grinding vehicle, the random vibration simulation analysis of the grinding vehicle is carried out under the condition of the horizontal irregularity of the American AAR6 track. Finally, by replacing the Q235 steel frame material with 7075 aluminum alloy and LA43M magnesium alloy, both vibration control and lightweight design can be achieved simultaneously. The results of transient dynamic response analysis show that the acceleration of most positions in the two working conditions exceeds the standard value in GB/T 17426-1998 standard. By optimizing the structure of the grinding vehicle in three ways, the average vibration acceleration of the whole car is reduced by about 55.1% from 15.6 m/s2 to 7.0 m/s2. The results of random vibration analysis show that the grinding vehicle with Q235 steel frame does not meet the safety conditions of $$3\sigma$$ 3 σ . By changing frame material, the maximum vibration stress of the vehicle can be reduced from 240.7 MPa to 160.0 MPa and the weight of the grinding vehicle is reduced by about 21.7% from 1500 kg to 1175 kg. The modal analysis results indicate that the vibration control of the grinding vehicle can be realized by optimizing the structure and replacing the materials with lower stiffness under the premise of ensuring the overall strength. The study provides the basis for the development of lightweight, diversified and efficient rail grinding equipment.

Abstract Males and females have long shown disparities in body weight and height; yet, the underlying mechanisms influencing growth and development remain unclear. Male and female Zhedong White Geese (ZDW) geese have long been selected for large body size and egg production, respectively. This led to a large difference in body weight between males and females, making them a unique model for studying the effects of sex on growth and development. This study aimed to elucidate these mechanisms by comparing the transcriptomes of muscle and pituitary tissues in male and female ZDW geese to identify the critical genes responsible for the effects of sex on growth performance. Our analysis revealed 1101 differentially expressed genes (DEGs) in leg musculature (507 upregulated, 594 downregulated), 773 DEGs in breast musculature (311 upregulated, 462 downregulated), and 517 DEGs in the pituitary gland (281 upregulated, 236 downregulated) between male and female geese. These DEGs were significantly enriched in gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with endocrine metabolism (e.g., hormonal activities), muscle formation (e.g., sarcomere and myofibril), and bone formation (e.g., bone morphogenesis and cartilage formation). The upregulated genes in males were enriched in KEGG pathways involving nutrient digestion and absorption (vitamin and protein), as well as the secretion of digestive juices (gastric acid and bile). Through protein–protein interaction analyses, we also observed high-density gene networks related to muscle fiber development, calcium ion metabolism, mitochondrial respiratory chain, and bone development. Therefore, our multi-tissue transcriptome analysis provides a deeper understanding of the complex and systematic gender-driven effects on growth and development in geese. IGF1, GHRHR, and NCAPG-LCORL and pathways related to myogenesis might play vital roles in gender differences before hormones exert their effect.

Abstract Children's respiratory tract infection is a common disease affecting children's health, our purpose is to describe the epidemiological characteristics of common pathogens of children's respiratory tract infection in central Shandong, China, and compare them with those in other parts of world, so as to summarize the rules of children's respiratory tract infection in central Shandong, and provide scientific basis for health departments to prevent and treat local children's respiratory tract infection. Sputum, tracheal aspirate, alveolar lavage fluid and other samples of 4804 children admitted to wards of Zibo Maternal and Child Health Hospital for treatment of respiratory tract infection from June 2019 to December 2022 were collected, and 12 common respiratory tract pathogens were detected by PCR capillary electrophoresis fragment analysis, two bacteria (Streptococcus pneumoniae, Haemophilus influenzae), two atypical pathogens (Mycoplasma Pneumoniae, Chlamydia Pneumoniae) and eight viruses (Human rhinovirus, Respiratory Syncytial Virus, Influenza A Virus, Parainfluenza Virus, Human metapneumovirus, Human boca virus, Human coronavirus, Influenza B virus) were included, the positive detection rate of single pathogen, the proportion of each type of respiratory tract mixed infection and the positive detection rate of single pathogen in different ages and seasons were analyzed statistically. (1)Among 4804 children with respiratory tract infection, the total positive rate was 77.87% (3741/4804), the positive rate of single pathogen was 43.40% (1656/4804), Streptococcus pneumoniae, Rhinovirus and Respiratory syncytial virus were the highest, there were 2085 cases of mixed infection with two or more pathogens, the positive rate was 43.40%. (2) The positive rates of infection in infant group (0–1 years old), infant group (1–3 years old), preschool group and school age group (3 years old-) were roughly the same, the infection rates of Streptococcus pneumoniae, Respiratory syncytial virus and Parainfluenza virus in infant group, Rhinovirus in infant group, Influenza A virus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Haemophilus influenzae in school age group were higher than those in other groups, the difference was statistically significant (P

Abstract Background Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. Methods To investigate the association between a patient’s responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. Results We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection. Conclusion Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Abstract Background Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms. Methods 5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells. Results The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells. Conclusions The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.

Abstract Background Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. Methods This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ 2). Sensitivity analysis was conducted on normal birth weight infants (2.5–4.0 kg). Results Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (

To assure operational safety in the airport apron area and track the process of ground service, it is necessary to analyze key targets and their activities in the airport apron surveillance videos. This research shows an activity identification algorithm for ground service objects in an airport apron area and proposes an improved YOLOv5 algorithm to increase the precision of small object detection by introducing an SPD-Conv (spath-to-depth-Conv) block in YOLOv5's backbone layer. The improved algorithm can efficiently extract the information features of small-sized objects, medium-sized objects, and moving objects in large scenes, and it achieves effective detection of activities of ground service in the apron area. The experimental results show that the detection average precision of all objects is more than 90%, and the whole class mean average precision (mAP) is 98.7%. At the same time, the original model was converted to TensorRT and OpenVINO format models, which increased the inference efficiency of the GPU and CPU by 55.3 and 137.1%, respectively.

In order to accurately predict the compressive strength of cement-based grouting material by small diameter core sample method, the compressive strength tests of cement-based grouting material standard size test blocks and small diameter core samples were carried out by pressure testing machine, and based on the test data, support vector machine regression (SVR) and random forest regression (RFR) were used to predict the compressive strength of cement-based grouting material. The results show that the standard size test blocks all show the failure pattern of the quadrangular cone with positive and negative continuation, while the small diameter core samples with a high diameter ratio of 0.7 and 1.0 show a cone failure form with positive and negative connections, and the small diameter core samples with a high diameter ratio of 1.2 show an oblique crack shear failure form; The compressive strength values of standard size test blocks and small diameter core samples all follow a normal distribution and have no outliers; As the age increases, the compressive strength of standard size test blocks and small diameter core samples increases, and they have the characteristics of higher early strength; The compressive strength of the core sample with a diameter of 46 mm is less and more susceptible to the influence of machining accuracy; At a given age and diameter, the compressive strength value of the core sample with a high diameter ratio of 0.7 is the largest, and the degree of dispersion of compressive strength is the smallest; The RFR prediction model has a better effect on the compressive strength of cement-based grouting material. The proposed method can accurately predict the compressive strength of cement-based grouting material, which provides some reference for the prediction and research of compressive strength of cement-based grouting material.

IgA deficiency allergic transfusion reaction often occurs in patients with anti-IgA. When blood products containing IgA are transfused into these patients, it may lead to severe allergic transfusion reactions, which can be fatal in severe cases. This review summarizes the clinical manifestations and influencing factors of immunoglobulin A deficiency (IgAD), as well as the pathogenesis, laboratory test and prevention strategies of allergic transfusion reactions caused by IgA deficiency, so as to enhance prevention awareness of IgA deficiency allergic transfusion reaction in medical staff.

Reducing the formation of large carbon clusters during the combustion of energetic materials (EMs) and improving their comprehensive performance hold great significance. With fluororubber (F2604) as a binder, this study prepared HNS/n-Al microspheres with different n-Al contents (5%, 10%, and 15%) using droplet microfluidic technology. Then, it characterized and tested the morphology, particle size distribution, dispersibility, crystal structure, thermal properties, mechanical sensitivity, and combustion behavior of the microspheres. The results show that the prepared microspheres had regular shapes, uniform particle sizes, and excellent dispersibility and contained more homogeneous components than physically mixed samples. Furthermore, the microspheres retained the crystal structures of the raw materials, enjoying high safety performance. The thermal analysis shows that HNS/n-Al microspheres had high heat resistance (thermal decomposition temperature: over 354 °C) and that a higher n-Al content was associated with more thorough thermal decomposition reactions of HNS (HNS: 83%, HNS/n-Al: 84%, 86%, and 93%). The ignition experiments show that the HNS/n-Al microspheres possessed excellent and stable combustion performance, as evidenced by more complete combustion reactions and significantly elevated energy release efficiency. Therefore, it is expected to achieve high-energy and high-speed responses of carbon-rich EMs and promote their practical applications.

Abstract Accurate prediction of oocyte maturation is a critical determinant of success in in vitro fertilization-embryo transfer (IVF-ET) procedures. This review provides a comprehensive analysis of the various predictive approaches employed to assess oocyte maturity, including single indicators, combined indicators, and predictive models. Factors such as ovarian reserve, patient characteristics, and controlled ovarian hyperstimulation (COH) strategies can significantly influence oocyte maturation rates. Single indicators, including hormone levels, ultrasound parameters, and clinical parameters, have been extensively studied. However, their predictive power may be limited when used in isolation. Combined indicators, integrating multiple parameters, have demonstrated improved predictive performance compared to single indicators. Additionally, predictive models and algorithms, such as machine learning and deep learning models, have emerged as promising tools for assessing oocyte maturity. These models leverage advanced statistical and computational methods to analyze complex datasets and identify patterns that can predict oocyte maturation rates with potentially higher accuracy. Despite these advancements, several gaps and limitations persist, including limited generalizability, lack of standardization, insufficient external validation, and the need to incorporate patient-specific factors and emerging technologies. The review highlights potential areas for further research, such as multicenter collaborative studies, integration of advanced omics technologies, development of personalized prediction models, and investigation of trigger time optimization strategies. Recommendations for clinical practice include utilizing a combination of indicators, adopting validated predictive models, tailoring approaches based on individual patient characteristics, continuous monitoring and adjustment, and fostering multidisciplinary collaboration. Accurate prediction of oocyte maturation holds profound implications for improving the success rates of IVF-ET and enhancing the chances of achieving a healthy pregnancy. Continued research, innovative approaches, and the implementation of evidence-based practices are essential to optimize assisted reproductive outcomes.

Abstract Radish exhibits significant variation in color, particularly in sprouts, leaves, petals, fleshy roots, and other tissues, displaying a range of hues such as green, white, red, purple, and black. Although extensive research has been conducted on the color variation of radish, the underlying mechanism behind the variation in radish flower color remains unclear. To date, there is a lack of comprehensive research investigating the variation mechanism of radish sprouts, leaves, fleshy roots, and flower organs. This study aims to address this gap by utilizing transcriptome sequencing to acquire transcriptome data for white and purple radish flowers. Additionally, the published transcriptome data of sprouts, leaves, and fleshy roots were incorporated to conduct a systematic analysis of the regulatory mechanisms underlying anthocyanin biosynthesis in these four radish tissues. The comparative transcriptome analysis revealed differential expression of the anthocyanin biosynthetic pathway genes DFR, UGT78D2, TT12 and CPC in the four radish tissues. Additionally, the WGCNA results identified RsDFR.9c and RsUGT78D2.2c as hub genes responsible for regulating anthocyanin biosynthesis. By integrating the findings from the comparative transcriptome analysis, WGCNA, and anthocyanin biosynthetic pathway-related gene expression patterns, it is hypothesized that genes RsDFR.9c and RsUGT78D2.2c may serve as pivotal regulators of anthocyanins in the four radish tissues. Furthermore, the tissue-specific expression of the four copies of RsPAP1 is deemed crucial in governing anthocyanin synthesis and accumulation. Our results provide new insights into the molecular mechanism of anthocyanin biosynthesis and accumulation in different tissues of radish.

Abstract Background Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. Methods We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. Results High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). Conclusions Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.

Abstract Objective Pulmonary papillary adenoma is an extremely rare benign tumor. It is derived from type II lung cells and club cells, suggesting that it may originate from stem cells with two-way differentiation. Only one case has been reported with FGFR2-IIIb overexpression. Methods Two cases of pulmonary papillary adenoma with available data on clinical features, histological morphology, immunophenotype and molecular characteristics were analyzed. Results Both tumors were well-circumscribed unencapsulated nodules composed of papillary structures with fibrovascular cores lined by a single layer of cuboidal or columnar epithelium without necrosis, nuclear atypia and mitoses, or invasion. But malignant transformation features include complex branching structures and significantly enlarged, irregular, and crowded malignant cells in one case. Immunohistochemistry showed that the tumor cells were strongly positive for TTF1, NapsinA, EMA and CK7 and negative for CEA and P63, with a low Ki-67 proliferation index. The EGFR somatic mutation exon19:c.2236_2256delinsATC (p.E746_S752delinsI) was found in one case by next-generation sequencing (NGS) technology. Conclusion Pulmonary papillary adenoma is very rare. Virtually all papillary adenomas are clinically silent and discovered incidentally. They are benign tumors, and resection is curative. An EGFR 19 exon deletion mutation in a patient with this tumor type was detected for the first time by NGS, and our results suggest that the malignant transformation of pulmonary papillary adenoma may be mediated by EGFR mutation.

The ocean is the largest carbon pool on earth and plays an important role in the global carbon cycle. Marine organisms contribute over half of the global carbon fixed by photosynthesis every year. Therefore, much attention has been paid to the role of the ocean in the carbon cycle and carbon sequestration. Macroalgae are an important component of coastal ecosystems, with strong and highly efficient carbon fixation capacity. The net primary productivity (NPP) of macroalgae was higher than that of phytoplankton and other primary producers in coastal waters. Parts of the photosynthates are released into the sea in the form of dissolved organic carbon (DOC) and particulate organic carbon (POC) during algae growth. Dissolved organic carbon and POC have attracted widespread attention because they can play important roles in carbon cycling and carbon sequestration in coastal ecosystems. However, the organic carbon release rate of macroalgae, its relationship with primary productivity, and the regulatory factors require further study. The growth of algae and the organic carbon release are influenced by temperature, light intensity, photoperiod, and other factors. However, organic carbon release rates among algae species might be quite different. Therefore, studying the regulatory effects of different factors on organic carbon release by algae and organic carbon release rate distribution has important implications for quantitatively evaluating the organic carbon release ability of algae and its contribution to the coastal ecosystem carbon cycle.In recent years, Sargassum horneri is the most common wild macroalgae in the Yellow Sea. Its ecological role in the coastal ecosystem has attracted widespread attention. Few studies have focused on organic carbon release by S. horneri. This study conducted an orthogonal experiment to measure DOC and POC release rates of S. horneri at different temperatures (5, 15, and 25 ℃), light intensity [86, 172, and 258 μmol/(m2·s)] and photoperiod (L: D=6 h: 18 h, L: D=12 h: 12 h, L: D=24 h: 0 h, L means light time, D means dark time) to study the organic carbon release rate of S. horneri, its relationship with NPP, and the main regulatory factors. The release rates of DOC were 0.653–4.785 mg/(g·h) and the release rates of POC were 0.066–0.322 mg/(g·h). There is an order of magnitude difference between DOC and POC. This indicated that DOC was the main form of organic carbon released by S. horneri. The highest DOC release rate [4.785 mg/(g·h)] occurred at 25 ℃, 172 μmol/(m2·s) light intensity, and L: D = 6 h: 18 h. The highest POC release rate [0.322 mg/(g·h)] occurred at 25 ℃, 258 μmol/(m2·s) light intensity, and L: D = 24 h: 0 h. The organic carbon release ability of S. horneri is consistent with previous studies of other macroalgae.This study found that changes in temperature and light conditions significantly affect the ability of S. horneri to release organic carbon. Temperature was the main factor affecting the release rate of DOC; the DOC release rate increases with increasing temperature. The DOC release rate initially increases, then decreases with increasing light intensity; it increases with a decrease in the photoperiod. Light intensity was the main factor influencing the POC release rate; increasing light intensity and photoperiod accelerated the POC release rate. However, the POC release rate slightly decreased when the light intensity increased from 172 to 258 μmol/(m2·s). There was a greater POC release rate under extreme temperature stress (5 and 25 ℃).This study showed that a proportion of DOC and POC in NPP were unstable in macroalgae. The range of DOC/NPP was 4%–130%. POC/NPP was relatively concentrated to approximately 0.4%–5.9%. The NPP was significantly lower in the experimental group with a high ratio of organic carbon compared with other experimental groups. The DOC release rate negatively correlated with NPP, but the negative correlation was poor in the low temperature groups. There was no significant correlation between the POC release rate and NPP. POC/NPP was relatively stable [approximately (1±0.6)% when NPP>9 mg C/(g·h)]. The growth pressure of S. horneri was high when NPP

Abstract A positive Indian Ocean Dipole features an anomalously high west-minus-east sea surface temperature gradient along the equatorial Indian Ocean, affecting global extreme weathers. Whether the associated impact spills over to global economies is unknown. Here, we develop a nonlinear and country-heterogenous econometric model, and find that a typical positive event causes a global economic loss that increases for further two years after an initial shock, inducing a global loss of hundreds of billion US dollars, disproportionally greater to the developing and emerging economies. The loss from the 2019 positive event amounted to US$558B, or 0.67% in global economic growth. Benefit from a negative dipole event is far smaller. Under a high-emission scenario, a projected intensification in Dipole amplitude causes a median additional loss of US$5.6 T at a 3% discount rate, but likely as large as US$24.5 T. The additional loss decreases by 64% under the target of the Paris Agreement.

Abstract Transition metal compounds with kagome structure have been found to exhibit a variety of exotic structural, electronic, and magnetic orders. These orders are competing with energies very close to each other, resulting in complex phase transitions. Some of the phases are easily observable, such as the charge density wave (CDW) and the superconducting phase, while others are more challenging to identify and characterize. Here we present magneto-transport evidence of a new phase below ~ 35 K in the kagome topological metal CsV3Sb5 (CVS) thin flakes between the CDW and the superconducting transition temperatures. This phase is characterized by six-fold rotational symmetry in the in-plane magnetoresistance (MR) and is connected to the orbital current order in CVS. Furthermore, the phase is characterized by a large in-plane negative magnetoresistance, which suggests the existence of a three-dimensional, magnetic field-tunable orbital current ordered phase. Our results highlight the potential of magneto-transport to reveal the interactions between exotic quantum states of matter and to uncover the symmetry of such hidden phases.

Abstract Background Overdose-related suicide attempts represent a significant portion of self-harm presentations in the psychiatric emergency department (ED). Identifying specific patient characteristics associated with these attempts holds promise for pinpointing drug classes with elevated risk and paving the way for tailored suicide prevention interventions. This study aims to examine the demographic profiles of ED patients who had experienced overdose-related suicide attempts. Methods This retrospective study was conducted at Beijing Anding Hospital, Capital Medical University, from January 2020 to December 2021. Patients with psychiatric drug overdose suicide attempts presenting to the psychiatric ED were included. Sociodemographic characteristics and the specific classes of drugs involved were collected, and analysed descriptively. Results This study examined 252 overdose patients, excluding 51 patients treated with alcohol or nonpsychiatric drugs, and a total 201 cases were included. The mean age of the patients was 28 ± 16 years (median 23, range 12–78), and 82% (n = 165) of the sample were females. Notably, nearly half (45%) of the patients were aged ≤ 20 years. While the number of cases decreased with increasing age, a significant increase was observed in 2021 compared to 2020. Benzodiazepines (BZDs) were the most frequently implicated substance class (n = 126, 63%), followed by antidepressants (n = 96, 48%), antipsychotics (n = 44, 22%), Z-drugs (n = 43, 21%), and mood stabilizers (n = 36, 18%). For adolescents, antidepressants (n = 52, 71%) overtook BZDs (n = 38, 52%) as the most common drug. The monthly distribution of cases revealed peaks in April and November. Furthermore, 21% (n = 42) of patients ingested more than two psychotropic medications concurrently. Finally, approximately half (n = 92) of the patients required inpatient admission for further treatment. Comparisons between hospitalized and nonhospitalized patients did not reveal any significant differences. Conclusions The present study revealed a greater prevalence of suicide overdose attempts among young females receiving prescriptions for antidepressants and/or BZDs. This finding suggests a potential need for enhanced monitoring of suicidal behaviour in this specific population when prescribing psychotropic medications. These findings contribute to the growing body of knowledge regarding drug overdose suicide attempts in psychiatric emergency settings and underscore the importance of further research to develop targeted prevention interventions.

Complex disaster systems involve various components and mechanisms that could interact in complex ways and change over time, leading to significant deep uncertainty. Due to deep uncertainty, decision-makers have severe inadequacy of knowledge and often encounter unpredictable surprises that may emerge in the future, thus making it difficult to specify appropriate models and parameters to describe the system of interest. In this paper, we propose a dynamic exploratory hybrid modeling framework that fits data, models, and computational experiments together to simulate complex systems with deep uncertainty. In the framework, one needs to develop multiple plausible models from a hybrid modeling perspective and perform enormous computational experiments to explore the diversity of future scenarios. Real-time data is then incorporated into diverse forecasts to dynamically adjust the simulation system. This ultimately enables an ongoing modeling and analysis process in which deep uncertainty would be gradually mitigated. Our approach has been applied to a human-involved car-following system simulation under complex traffic conditions. The results show that the proposed approach can improve the prediction accuracy while enhancing the sensitivity of the simulation system to uncertain changes in the system of interest.

Abstract Hemibagrus guttatus, also named as spotted longbarbel catfish, is an economical fish in China. However, their gender cannot be easily distinguished from their appearance, which largely impedes their artificial breeding. Therefore, we provided two gap-free chromosome-level genomes of male and female spotted longbarbel catfish by combining wtdbg2, LR_Gapcloser and TGS-GapCloser assembly approaches with Hi-C data and accurate Pacbio HiFi long-reads. We assembled 30 chromosomes without any gap. Their genome sizes are approximately 749.1 Mb and 747.8 Mb of male and female individuals. The completeness results of BUSCO evaluation show about 94.2% and 95.0%, representing a high-level of completeness of both genomes. We also obtained 35,277 and 34,571 protein-coding gene sets from male and female individuals. Both available gap-free chromosome-level genomes of H. guttatus will provide excellent references for resequencing of male and female individuals to identify accurate markers for distinguishing gender of this fish.

Abstract The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option. Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

Abstract Background We aimed to explore the association and potential causality between polyunsaturated fatty acids concentrations and the risk of periodontal disease. Materials and methods Data were collected from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression analysis and restricted cubic spline (RCS) analysis were used to analyse the associations of the concentrations of omega-3 and omega-6 fatty acids and the omega-6/omega-3 fatty acids ratio with the risk of periodontitis. E-value and propensity score matching (PSM) analyses were used for sensitivity analyses. In addition, two-sample Mendelian randomisation (MR) analyses were performed to assess the potential causal impact of the concentrations of those fatty acids on periodontitis risk. Results A total of 2462 participants from the NHANES were included. Logistic regression analysis revealed that high omega-3 fatty acids levels were negatively associated with the risk of developing periodontitis (P 0.05). Conclusion Although omega-3 fatty acids and the omega-6/omega-3 fatty acids ratio were associated with the risk of periodontitis in cross-sectional studies, the MR results did not support a causal relationship between them. Therefore, there is no indication that an increase in the omega-3 fatty acids concentration or a decrease in the omega-6/omega-3 fatty acids ratio may be beneficial for preventing periodontitis.