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Abstract Background Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture. Methods Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases. Results A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3–8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4–34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p

Abstract Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell’s stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271–4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166–4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303–0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants.

Abstract Background Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. Methods In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. Results 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (β=-0.0121, P

Abstract Due to high computation complexity, traditional design methods for LLC converter usually consider limited kinds of performance, and the process for searching the optimal parameter scheme is discrete, which might cause the missing of real optimal solution. In order to solve these problems, a multi‐objectives optimization design method for the LLC converter is proposed in this paper. According to the numerical calculation method, a closed parameter space for resonant parameters is established under the constraints of operation mode, switching frequency, zero voltage switching (ZVS), and voltage stress of resonant capacitor. Besides, the root‐mean‐square (RMS) value of resonant current and secondary current, as well as the core loss of the transformer, are selected as the optimization objectives. Non‐dominated sorting genetic algorithm (NSGA‐II) is utilized to deal with these multi‐objective formulations. In order to reduce the computation complexity, a data‐driven method, called adaptive polynomial approximation (APA), is selected to obtain the explicit expressions of the parameter space and the optimization objectives. Then, by substituting this simplified surrogate model into the NSGA‐II algorithm, the optimal parameter scheme is obtained. The comprehensive comparison analysis is performed, and a 400 W/48 V experimental prototype was built to verify the theoretical analysis, which shows that the proposed method features the highest efficiency of 95%.

Abstract Objectives Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. Methods Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. Results High-sensitivity C-reactive protein (p

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Abstract In traditional von Neumann computing architecture, the efficiency of the system is often hindered by the data transmission bottleneck between the processor and memory. A prevalent approach to mitigate this limitation is the use of non-volatile memory for in-memory computing, with spin–orbit torque (SOT) magnetic random-access memory (MRAM) being a leading area of research. In this study, we numerically demonstrate that a precise combination of damping-like and field-like spin–orbit torques can facilitate precessional magnetization switching. This mechanism enables the binary memristivity of magnetic tunnel junctions (MTJs) through the modulation of the amplitude and width of input current pulses. Building on this foundation, we have developed a scheme for a reconfigurable spintronic logic gate capable of directly implementing Boolean functions such as AND, OR, and XOR. This work is anticipated to leverage the sub-nanosecond dynamics of SOT-MRAM cells, potentially catalyzing further experimental developments in spintronic devices for in-memory computing.

Abstract Introduction The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet. Material and methods The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs. Results The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714–0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440–0.767), other models’ AUCs displayed well. Thereinto, the RF algorithm’s final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693–0.949). Conclusion The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy.

Abstract Background Terpenes are important components of plant aromas, and terpene synthases (TPSs) are the key enzymes driving terpene diversification. In this study, we characterized the volatile terpenes in five different Chrysanthemum nankingense tissues. In addition, genome-wide identification and expression analysis of TPS genes was conducted utilizing an improved chromosome-scale genome assembly and tissue-specific transcriptomes. The biochemical functions of three representative TPSs were also investigated. Results We identified tissue-specific volatile organic compound (VOC) and volatile terpene profiles. The improved Chrysanthemum nankingense genome assembly was high-quality, including a larger assembled size (3.26 Gb) and a better contig N50 length (3.18 Mb) compared to the old version. A total of 140 CnTPS genes were identified, with the majority representing the TPS-a and TPS-b subfamilies. The chromosomal distribution of these TPS genes was uneven, and 26 genes were included in biosynthetic gene clusters. Closely-related Chrysanthemum taxa were also found to contain diverse TPS genes, and the expression profiles of most CnTPSs were tissue-specific. The three investigated CnTPS enzymes exhibited versatile activities, suggesting multifunctionality. Conclusions We systematically characterized the structure and diversity of TPS genes across the Chrysanthemum nankingense genome, as well as the potential biochemical functions of representative genes. Our results provide a basis for future studies of terpene biosynthesis in chrysanthemums, as well as for the breeding of improved chrysanthemum varieties.

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes, its therapeutic potential is compromised by its short half-life and narrow therapeutic index. Current long-acting insulin analogs, such as insulin-polymer conjugates, are mainly used to improve pharmacokinetics by reducing renal clearance. However, these conjugates are synthesized without sacrificing the bioactivity of insulin, thus retaining the narrow therapeutic index of native insulin, and exceeding the efficacious dose still leads to hypoglycemia. Here, we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance. By impairing the binding affinity to the receptor and the activation of the receptor, di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly, increases its maximum tolerated dose 10-fold. The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose. This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

BackgroundSilicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO2). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. ObjectiveTo investigate the effects of different concentrations of Bru on SiO2-induced silicosis fibrosis in mice. MethodsThirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg−1), with 6 mice in each group. Except the control group, the remaining groups were established as SiO2-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL−1 SiO2 suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. ResultsCompared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). ConclusionLow and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO2-induced silicosis mice.

On February 6, 2023, the doublet earthquake including two main shocks with magnitudes MW7.8 and MW7.5, occurred near the western side of the East Anatolian Fault at the southeast boundary of the Anatolian Plateau in Turkey. Based on the WGM2012 Bouguer gravity anomaly data and the Etopo1 topography data, this study first introduced a joint inversion of admittance and coherence functions and used the Bayesian optimal parameter estimation method to obtain the effective elastic thickness Te and loading ratio F of the lithosphere for various tectonic units in the Anatolian Plateau. Secondly, we discussed the characteristics and influencing factors of the lithospheric mechanical strength and analyzed its relationship with seismic activity. The lithospheric mechanical strength of the Anatolian Plateau showed clear lateral heterogeneity and a ''weak-strong-weak'' spatial pattern from east to west, reflecting various tectonic processes. At last, the strong seismic activity was found where the lithospheric strength was low in the Anatolian Plate. We also incorporated GPS strain rate and other results to investigate the tectonic background and primary causes of the MW7.8 and MW7.5 doublet earthquakes in Turkey. The results have a good insight into urban safety design in the Turkish region, including post-disaster rehabilitation, earthquake hazard assessment, and loss reduction.

Manganese cobaltite (MnCo2O4) is a promising electrode material because of its attractive redox chemistry and excellent charge storage capability. Our previous work demonstrated that the octahedrally-coordinated Mn are prone to react with the hydroxyl ions in alkaline electrolyte upon electrochemical cycling and separates on the surface of spinel to reconstruct into δ-MnO2 nanosheets irreversibly, thus results in a change of the reaction mechanism with K+ ion intercalation. However, the low capacity has greatly limited its practical application. Herein, we found that the tetrahedrally-coordinated Co2+ ions were leached when MnCo2O4 was equilibrated in 1 mol L−1 HCl solution, leading to the formation of layered CoOOH on MnCo2O4 surface which is originated from the covalency competition induced selective breakage of the CoT–O bond in CoT–O–CoO and subsequent rearrangement of free CoO6 octahedra. The as-formed CoOOH is stable upon cycling in alkaline electrolyte, exhibits conversion reaction mechanism with facile proton diffusion and is free of massive structural evolution, thus enables utilization of the bulk electrode material and realizes enhanced specific capacity as well as facilitated charge transfer and ion diffusion. In general, our work not only offers a feasible approach to deliberate modification of MnCo2O4's surface structure, but also provides an in-depth understanding of its charge storage mechanism, which enables rational design of the spinel oxides with promising charge storage properties.

Abstract Background This study assesses the prevalence of sexually transmitted infections (STIs) in first time visitors to the STIs clinic in Hangzhou, China, considering different genders, ages and symptoms. And also explores howthe COVID‐19 pandemic has affected on STIs. Methods From 2019 to 2023, 27,283 first time visitors were tested for nine distinct STIs, including Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), syphilis, Herpes Simplex Virus type 2 (HSV‐2), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and vaginal Candida. Results Symptomatic male and female visitors showed overall STI‐positive rates of 39.27% and 59.20%, respectively(p 50 years, regardless of gender and symptoms. During the COVID‐19 pandemic, symptomatic visitors showed lower positive rates for HPV, HIV, syphilis, and HSV‐2, while Candida, UU, CT, NG, and multiple infections increased. Among asymptomatic visitors, HPV had the lowest positive rate, while NG and multiple infections increased during the pandemic. Conclusion STI prevalence is notably high, particularly in those aged ≤ 20 and >50 years. It emphasizes the need for enhanced health education, condom use, and vaccination. The COVID‐19 pandemic impacting STIs through varied factors, such as reduced sexual activity and clinical service interruption.

Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease that presents with the proliferation of extensive, dense fibrous tissue in the mediastinum. Hemoptysis is a common clinical manifestation of FM. Clinically, most patients exhibit mild to moderate hemoptysis. We report a case of FM complicated with life-threatening massive hemoptysis. The patient was successfully rescued through a combination of bronchoscopic balloon closure, bronchial artery embolization (BAE), and surgical interventions. Although FM is frequently benign, vascular involvement can progress to life-threatening massive hemoptysis and must be treated appropriately.

ABSTRACT: Free gossypol (FG), the primary antinutritional component in cottonseed meal, can adversely affect the growth and health of poultry. Although younger geese are particularly sensitive to FG, the precise effects of FG on geese remain elusive. This study aimed to investigate the effects of gossypol acetate (GA), a form of FG, on the growth, serum biochemical parameters, and intestinal health of goslings. Seventy-two healthy male goslings, aged 7-day-old with similar body weight (BW), were randomly divided into 3 groups: a control group and 2 GA-treated groups (GA25 and GA50), which were orally administered GA (25 and 50 mg/kg BW) daily for 14 d. The results showed that oral administration of GA significantly suppressed BW, altered serum parameters, and impaired intestinal health in a dose- and time-dependent manner. Specifically, GA adversely affected intestinal morphology, induced oxidative stress, and inflammation, diminished immune function, and increased intestinal permeability and apoptosis of intestinal cells, consequently impairing nutrient absorption and utilization of goslings. Overall, these data indicate that GA adversely affects the growth, serum parameters, and intestinal health of goslings, providing valuable information further to understand the toxic effects of gossypol on goslings.

Mathematical modeling of epidemic dynamics is crucial to understand its underlying mechanisms, quantify important parameters, and make predictions that facilitate more informed decision-making. There are three major types of models: mechanistic models including the SEIR-type paradigm, alternative data-driven (DD) approaches, and hybrid models that combine mechanistic models with DD approaches. In this paper, we summarize our work in the COVID-19 Scenario Modeling Hub (SMH) for more than 12 rounds since early 2021 for informed decision support. We emphasize the importance of deep learning techniques for epidemic modeling via a flexible DD framework that substantially complements the mechanistic paradigm to evaluate various future epidemic scenarios. We start with a traditional curve-fitting approach to model cumulative COVID-19 based on the underlying SEIR-type mechanisms. Hospitalizations and deaths are modeled as binomial processes of cases and hospitalization, respectively. We further formulate two types of deep learning models based on multivariate long short term memory (LSTM) to address the challenges of more traditional DD models. The first LSTM is structurally similar to the curve fitting approach and assumes that hospitalizations and deaths are binomial processes of cases. Instead of using a predefined exponential curve, LSTM relies on the underlying data to identify the most appropriate functions, and is capable of capturing both long-term and short-term epidemic behaviors. We then relax the assumption of dependent inputs among cases, hospitalizations, and death. Another type of LSTM that handles all input time series as parallel signals, the independent multivariate LSTM, is developed. Independent multivariate LSTM can incorporate a wide range of data sources beyond traditional case-based epidemiological surveillance. The DD framework unleashes its potential in big data era with previously neglected heterogeneous surveillance data sources, such as syndromic, environment, genomic, serologic, infoveillance, and mobility data. DD approaches, especially LSTM, complement and integrate with the mechanistic modeling paradigm, provide a feasible alternative approach to model today’s complex socio-epidemiological systems, and further leverage our ability to explore different scenarios for more informed decision-making during health emergencies.

Media multitasking is widespread, yet its relationship with creativity remains unclear. This study employs a combination of measures, including the media multitasking questionnaire, alternative uses task (AUT) for divergent thinking, Chinese compound remote association task (CCRAT) for convergent thinking, and a creative problem-solving task, to examine the relationship between media multitasking and creativity. Extreme values grouping [one standard deviation above or below the mean of the media multitasking index (MMI)], median value grouping, and regression analysis were used to explore the relationship between media multitasking and creativity. The results revealed the following findings: (1) across the three analysis methods, there was no significant relationship between media multitasking and performance on the AUT task. However, within the range of one standard deviation above or below the mean of the MMI, media multitasking showed a significant positive correlation with fluency, flexibility, and total scores on the AUT task. (2) Media multitasking significantly predicted the accuracy of responses on the CCRAT task positively. (3) Media multitasking significantly predicted lower scores on the applicability of creative problem-solving tasks.

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH.MethodsSingle-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining.ResultsThe results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression.ConclusionCD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

Abstract Genomic instability is not only a hallmark of senescent cells but also a key factor driving cellular senescence, and replication stress is the main source of genomic instability. Defective prelamin A processing caused by lamin A/C (LMNA) or zinc metallopeptidase STE24 (ZMPSTE24) gene mutations results in premature aging. Although previous studies have shown that dysregulated lamin A interferes with DNA replication and causes replication stress, the relationship between lamin A dysfunction and replication stress remains largely unknown. Here, an increase in baseline replication stress and genomic instability is found in prelamin A‐expressing cells. Moreover, prelamin A confers hypersensitivity of cells to exogenous replication stress, resulting in decreased cell survival and exacerbated genomic instability. These effects occur because prelamin A promotes MRE11‐mediated resection of stalled replication forks. Fanconi anemia (FA) proteins, which play important roles in replication fork maintenance, are downregulated by prelamin A in a retinoblastoma (RB)/E2F‐dependent manner. Additionally, prelamin A inhibits the activation of the FA pathway upon replication stress. More importantly, FA pathway downregulation is an upstream event of p53‐p21 axis activation during the induction of prelamin A expression. Overall, these findings highlight the critical role of FA pathway dysfunction in driving replication stress‐induced genomic instability and cellular senescence in prelamin A‐expressing cells.

Summary: Background: The triglyceride-glucose (TyG) index has been recognized as a crucial risk factor for cardiovascular diseases. However, the association between the TyG index and mortality in the general population remains elusive. Methods: Participants were enrolled from the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART), a nationwide prospective cohort study. The outcomes of interest were all-cause, cardiovascular, and cancer mortality. Restricted cubic splines and Cox regression models were used to assess the associations between the TyG index and outcomes. Findings: In total, 3,524,459 participants with a median follow-up of 4.6 (IQR, 3.1–5.8) years were included. The associations of the TyG index with all-cause and cardiovascular mortality were reverse L-shaped, with cut-off values of 9.75 for all-cause mortality and 9.85 for cardiovascular mortality. For each 1-unit increase in the TyG index, when below the cut-off values, the TyG index was not significantly associated with all-cause mortality (HR = 1.02, 95% CI: 1.00–1.03) and was only modestly associated with cardiovascular mortality (HR = 1.09, 95% CI: 1.06–1.11). Conversely, when the cut-off values were exceeded, the HRs (95% CI) were 2.10 (1.94–2.29) for all-cause mortality and 1.99 (1.72–2.30) for cardiovascular mortality. However, the association between the TyG index and cancer mortality was linearly negative (HR = 0.97, 95% CI: 0.94–0.99). Interpretation: The associations of the TyG index with all-cause and cardiovascular mortality displayed reverse L-shaped patterns, while an elevated TyG index showed a slight negative association with cancer mortality. We suggest that

Abstract Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

Abstract Background With the dramatic uplift of the Qinghai–Tibet Plateau (QTP) and the increase in altitude in the Pliocene, the environment became dry and cold, thermophilous plants that originally inhabited ancient subtropical forest essentially disappeared. However, Quercus sect. Heterobalanus (QSH) have gradually become dominant or constructive species distributed on harsh sites in the Hengduan Mountains range in southeastern QTP, Southwest China. Ecological stoichiometry reveals the survival strategies plants adopt to adapt to changing environment by quantifying the proportions and relationships of elements in plants. Simultaneously, as the most sensitive organs of plants to their environment, the structure of leaves reflects of the long-term adaptability of plants to their surrounding environments. Therefore, ecological adaptation mechanisms related to ecological stoichiometry and leaf anatomical structure of QSH were explored. In this study, stoichiometric characteristics were determined by measuring leaf carbon (C), nitrogen (N), and phosphorus (P) contents, and morphological adaptations were determined by examining leaf anatomical traits with microscopy. Results Different QSH life forms and species had different nutrient allocation strategies. Leaves of QSH plants had higher C and P and lower N contents and higher N and lower P utilization efficiencies. According to an N: P ratio threshold, the growth of QSH species was limited by N, except that of Q. aquifolioides and Q. longispica, which was limited by both N and P. Although stoichiometric homeostasis of C, N, and P and C: N, C: P, and N: P ratios differed slightly across life forms and species, the overall degree of homeostasis was strong, with strictly homeostatic, homeostatic, and weakly homeostatic regulation. In addition, QSH leaves had compound epidermis, thick cuticle, developed palisade tissue and spongy tissue. However, leaves were relatively thin overall, possibly due to leaf leathering and lignification, which is strategy to resist stress from UV radiation, drought, and frost. Furthermore, contents of C, N, and P and stoichiometric ratios were significantly correlated with leaf anatomical traits. Conclusions QSH adapt to the plateau environment by adjusting the content and utilization efficiencies of C, N, and P elements. Strong stoichiometric homeostasis of QSH was likely a strategy to mitigate nutrient limitation. The unique leaf structure of the compound epidermis, thick cuticle, well-developed palisade tissue and spongy tissue is another adaptive mechanism for QSH to survive in the plateau environment. The anatomical adaptations and nutrient utilization strategies of QSH may have coevolved during long-term succession over millions of years.

Abstract Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan–Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P/SLC7A11 axis.

Abstract Assessing the effectiveness of vegetation restoration along the Yangtze River shoreline and exploring its relationship with land use changes are imperative for providing recommendations for sustainable management and environmental protection. However, the impact of vegetation restoration post-implementation of the Yangtze River Conservation Project remains uncertain. In this study, utilizing Sentinel-2 satellite imagery and Dynamic World land use data from pre- (2016) and post- (2022) Yangtze River Conservation Project periods, pixel-based binary models, transition matrices, and geographically weighted regression models were employed to analyze the status and evolution of vegetation coverage along the Yangtze River shoreline. The results indicated that there had been an increase in the area covered by high and high-medium vegetation levels. The proportion of vegetation cover shifting to better was 4201.87 km2 (35.68%). Hotspots of vegetation coverage improvement were predominantly located along the Yangtze River. Moreover, areas witnessing enhanced vegetation coverage experienced notable land use changes, notably the conversion of water to crops (126.93 km2, 22.79%), trees to crops (59.93 km2, 10.76%), and crops to built area (59.93 km2, 10.76%). Notably, the conversion between crops and built area emerged as a significant factor influencing vegetation coverage improvement, with average regression coefficients of 0.68 and 0.50, respectively. These outcomes underscore the significance of this study in guiding ecological environmental protection and sustainable management along the Yangtze River shoreline.

This paper examines how businesses in Taiwan’s servicescapes are adapting to the growing trend of mobile payments and innovation ecosystems. Through the analysis of four case studies, we uncover the strategies these firms employ to address the challenges posed by changing consumer payment habits. Our research reveals that these companies are establishing efficient mechanisms within their ecosystems, supported by well-structured organizational frameworks. By leveraging innovation ecosystems, they are reshaping financial services and promoting collaborative growth among participants through technology, platforms, resource sharing, and knowledge exchange. This collaborative approach is driving significant changes in the sector, helping these businesses navigate through various challenges while fostering innovation and growth. Additionally, the scarcity of comprehensive observations of the digital payment ecosystem highlights the necessity for further exploration of actor interactions, regulatory mechanisms, and ecosystem management strategies. Such research efforts are crucial for enhancing our understanding of the evolving landscape of digital payments and innovation ecosystems, facilitating informed decision-making and promoting sustainable development in this dynamic industry.

Abstract Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.

Polyester fabric/polyvinyl chloride (PET/PVC) flexible composites were widely used in outdoor products such as sports and leisure, advertising and printing due to its light weight, high strength and good processability. However, under extreme weather conditions such as high temperature and high humidity for a long time, it was very easy to decrease the mechanical properties due to water absorption. Therefore, PET fabric was modified by fluorine-containing block copolymer, and then the wicking resistant PET fabric reinforced PVC resin matrix flexible composites (F-PET/PVC) were obtained by roll coating, then, the mechanism of hygrothermal aging was further explored. The results show that the water contact angle of PET fabric increases from 0° to 114.5°, the wicking height of F-PET/PVC decreases by about 94.29%, and the peeling performance decreases by about 15.87%, when the concentration of anti-wicking agent reaches 20 g/L. In addition, the hygrothermal aging test shows that the hygrothermal aging resistance of F-PET/PVC is better than that of PET/PVC, and the interfacial peeling strength and tensile strength loss rate is decreased from 7.41% and 3.61% to 3.08% and 0.48%, respectively. It is expected to provide a reference for the durability design of environmental fabric-reinforced resin matrix composites.

The Shunbei 5 (SB5) strike-slip fault, situated in the central Tarim basin, is distinguished by its considerable length, significant variations in planar orientation, and intricate multi-stage tectonic evolution. This study delves into the geometric, kinematic, and dynamic features of both the southern and northern parts of the SB5 fault, utilizing the latest seismic data from the Fuman Oilfield, and examines the factors influencing the fault’s planar deflection. The fault can be categorized into three structural deformation layers based on lithological features and fault features: the deep structural deformation layer (below TЄ3), characterized by basement rifting and limited strike-slip activity; the middle structural deformation layer (TЄ3-TO3), marked by vigorous strike-slip movements and the dominance of flower structures; and the shallow structural deformation layer (TO3-TP), featuring echelon-type normal faults and boundary graben faults, specifically in the southern SB5 fault. The fault activity is more pronounced in its southern SB5 fault compared to the northern, with the weakest activity at the TЄ3 interface and the peak at the TO3 interface. The southern SB5 fault transitions to sinistral slip at the TO3 interface, while the northern SB5 fault shifts from dextral to sinistral slip at the TC interface, highlighting variable slip directions across different interfaces. Rifts are extensively distributed within the Precambrian basement along the SB5 fault. The initial strike-slip fault rupture, which is primarily localized in these areas, exerts a significant influence on the formation of the S-shaped fault plane. This process involves four distinct evolution stages: the embryonic stage of strike-slip activity during the Middle-Late Cambrian; the intense strike-slip fault activity stage during the Middle-Late Ordovician; the reactivation stage of deep strike-slip fault in the Silurian; and the connection and reactivation stage during the Devonian-Carboniferous.

Abstract Studies on the associations of blood pressure (BP) and the risk of venous thromboembolism (VTE) had been performed neither among pregnant women nor in Chinese population. This study included participants of pregnant women from a retrospective multicenter cohort, between May 2020 and April 2023. Systolic BP (SBP) and diastolic BP (DBP) of the participants were measured in the third trimester. The incidences of VTE (including deep venous thrombosis and/or pulmonary embolism) at 42 days postpartum were followed. With regards to SBP, pregnant women in the Q1 (≤114 mmHg), Q2 (115–122 mmHg), and Q4 group (≥131 mmHg) had increased risk of VTE than those in Q3 group (123–130 mmHg), with ORs 4.48 [1.69, 11.85], 3.52 [1.30, 9.59], and 3.17 [1.12, 8.99], respectively. Compared with pregnant women with the Q4 of DBP (≥85 mmHg), women of Q1 (≤71 mmHg) were found to have elevated risk of VTE (OR 2.73 [1.25, 5.96]). A one standard deviation decrease of DBP (9 mmHg) was related with 37% elevated risk of VTE (OR 1.37 [1.05, 1.79]). This study demonstrated a U‐shaped association of SBP in the third trimester and VTE postpartum and inverse association of DBP in the third trimester and VTE postpartum.

BackgroundDysnatremia is the most common electrolyte disorder in hospitalized patients. Sodium fluctuation level may be a better parameter in dysnatremia management. We aimed to examine the association between sodium fluctuation level during hospitalization and mortality and to evaluate its value in predicting poor prognosis among general hospitalized patients.MethodsData were collected from patients admitted to Peking Union Medical College Hospital. The generalized estimated equation (GEE) was used to examine the relationship between sodium fluctuation level and mortality. Receiver-operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff value and the area under the ROC curve (AUC).ResultsSodium fluctuation level showed a dose-dependent association with increased mortality in general hospitalized patients. After adjusting age, sex, length of hospital stay, and Charlson comorbidity index, the ORs of group G2 to G6 were 5.92 (95% CI 5.16–6.79), 26.45 (95% CI 22.68–30.86), 50.71 (95% CI 41.78–61.55), 104.38 (95% CI 81.57–133.58), and 157.64 (95% CI 112.83–220.24), respectively, p trend

Abstract Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses. Toward this, several molecular and biochemical experiments are performed using patient‐derived organoid models and a KPC mouse model (LSL‐KrasG12D/+, LSL‐Trp53R172H/+, Pdx‐1‐Cre). It is observed that the inhibition of macrophage‐capping protein (MCP) suppressed the ubiquitin fold modifier (UFM)ylation of pirin (PIR), a newly identified substrate of UFM1, thereby decreasing the transcription of GPX4, a marker of ferroptosis, and promoting the cytoplasmic transportation of HMGB1, a damage‐associated molecular pattern. GPX4 deficiency triggered ferroptosis, and the pre‐accumulated cytosolic HMGB1 is released rapidly. This altered release pattern of HMGB1 facilitated the pro‐inflammatory M1‐like polarization of macrophages. Thus, therapeutic inhibition of MCP yielded dual antitumor effects by stimulating ferroptosis and activating antitumor pro‐inflammatory M1‐like macrophages. The nanosystem developed for specifically silencing MCP is a promising tool for treating PDAC.

Acute spontaneous subdural hematoma (SDH) of arterial origin is rare in the field of neurosurgery. We report a 57-year-old male patient developed sudden onset headache and right hemiparesis. He had no history of head trauma.A computed tomography demonstrated an acute left-sided SDH. A computed tomography angiogram (CTA) demonstrated active contrast extravasation from a small cortical middle cerebral artery (MCA) branch into the left-sided SDH. Endoscopic surgery was performed to evacuate the hematoma,we verified the arterial origin of the bleeding and coagulated the bleeding point. Postoperatively the patient’s symptoms clearly improved. He was discharged 7 days after surgery. In a case of acute spontaneous SDH, the possibility of a cortical artery origin should be considered, The initial radiologic investigation in a patient with a spontaneous acute SDH should be a CT and CTA. Endoscopic hematoma evacuation of acute spontaneous SDH may be a safe and effective method in some cases.

In the central Tarim Basin, numerous hydrocarbon deposits were found along ultra-deep strike-slip faults, and its evolving progress and formation mechanism are research hotspots. The Paleozoic small-angle X-type strike-slip fault in the Tabei Uplift is the research subject in this article. Based on high-precision three-dimensional seismic data, three structural deformation layers were revealed: the rift system, weak strike-slip deformation and salt tectonics in the deep structural layer (Sinian–Middle Cambrian), the strong strike-slip deformation and karst-dissolution structure in the middle structural layer (Upper Cambrian–Middle Ordovician), and echelon normal faults in the shallow structural layer (Upper Ordovician–Carboniferous). The formation and evolution of strike-slip faults is jointly controlled by the distribution pattern of basement rift and the activities of surrounding orogenic belts, which can be divided into three stages. In the Middle to Late Cambrian, the initial subduction of the Paleo-Asian and Proto-Tethyan oceans precipitated the emergence of two sets of small-angle X-type strike-slip faults, striking NW and NE above the grooves of Precambrian rifts, influenced by local weak compressive stress. Affected by the closure of peripheral paleo-ocean, strike-slip faults deformed considerably in the Middle–Late Ordovician and were reactivated in the Silurian–Carboniferous, forming en-echelon normal faults in the shallow layer. The layered deformation structure of the strike-slip faults significantly affects the accumulation of hydrocarbons. The differential hydrocarbon enrichment of faults in the Tabei Uplift is collectively influenced by the distribution of source rocks and the migration of oil and gas. The topographical features of the Tabei Uplift, along with the distribution of strike-slip faults across tectonic units, have rendered the NE direction the preferential pathway for hydrocarbon migration. Additionally, impacted by the development of en echelon faults, the NE-trending faults offer superior conditions for hydrocarbon preservation and charging condition, compared to the NW-trending faults.

BackgroundThe etiology of gallstone disease (GSD) has not been fully elucidated. Consequently, the primary objective of this study was to scrutinize and provisionally authenticate the distinctive expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in GSD.MethodsRiboNucleic Acid (RNA) sequencing was used on four paired human gallbladder samples for the purpose of this study. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified and subjected to analysis of their biological functions. The Pearson’s correlation coefficients between DElncRNAs and DEmRNAs were computed to construct a co-expression network delineating their associations. Furthermore, both cis- and trans-regulatory networks of selected lncRNAs were established and visualized. Additionally, a competing endogenous RNA (ceRNA) regulatory network was constructed. To validate the RNA-sequencing data, we performed a Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) on 10 paired human gallbladder samples, assessing the expressions of the top 4 DEmRNAs and DElncRNAs in gallstone and control samples.ResultsA total of 934 DEmRNAs and 304DElncRNAs were successfully identified. Functional enrichment analysis indicated a predominant involvement in metabolic-related biological functions. Correlation analysis revealed a strong association between the expressions of 597 DEmRNAs and 194 DElncRNAs. Subsequently, both a cis-lncRNA-mRNA and a trans-lncRNA-Transcription Factor (TF)-mRNA regulatory network were meticulously constructed. Additionally, a ceRNA network, comprising of 24 DElncRNAs, 201 DEmRNAs, and 120 predicted miRNAs, was established. Furthermore, using RT-qPCR, we observed significant upregulation of AC004692.4, HECW1-IT1, SFRP4, and COMP, while LINC01564, SLC26A3, RP1-27K12.2, and GSTA2 exhibited marked downregulation in gallstone samples. Importantly, these findings were consistent with the sequencing.ConclusionWe conducted a screening process to identify DElncRNAs and DEmRNAs in GSD. This approach contributes to a deeper understanding of the genetic factors involved in the etiology of gallstones.

Background: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program’s office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. Results: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. Conclusion: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Wind energy has become one of the most important measures for China to achieve its carbon neutrality goal. The spatial and temporal evolvement of economic competitiveness for wind energy becomes an important concern in shaping the decarbonization pathway in China. There has been an urgent need in power system planning to model the future dynamics of cost decline and supply potential for wind power in the context of carbon neutrality until 2060. Existing studies often fail to capture the rapid decline in the cost of wind power generation in recent years, and the prediction of wind power cost decline is more conservative than the reality. This study constructs an integrated model to evaluate the cost-competitiveness and grid parity potential of China's onshore wind electricity at fine spatial resolution with updated parameters. Results indicate that the total onshore wind potential amounts to 54.0 PWh. The average levelized cost of wind power is expected to decline from CNY 0.39 kWh−1 in 2020 to CNY 0.30 and CNY 0.21 kWh−1 in 2030 and 2060. 28.3%, 67.6%, and 97.6% of the technical potentials hold power costs lower than coal power in 2020, 2030, and 2060.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

Abstract The emergence of the Fifth Generation (5G) era has ushered in a new era of diverse business scenarios, primarily characterized by data-intensive and latency-sensitive applications. Edge computing technology integrates the information services environment with cloud computing capabilities at the edge of the network. However, the evolving landscape of business models necessitates a unified edge architecture capable of accommodating diverse requirements, posing substantial challenges for service providers in meeting Service-Level Agreements (SLAs).In response to these challenges, we introduce SLA-ORECS. This innovative framework dynamically allocates dedicated and shared resources within the edge-cloud system to cater to service requests with varying SLAs, thereby facilitating performance isolation. Furthermore, we have developed an optimization algorithm to enhance the efficiency of SLA assurance during request dispatch.The evaluation of SLA-ORECS highlights its noteworthy performance improvements, particularly in terms of system throughput and average time consumption.

Abstract Given the spatial resolution of ~300 km in Gravity Recovery and Climate Experiment (GRACE) measurements, accurately quantifying mass variations at smaller scales proves challenging. Here, we present a high-resolution time-variable gravity field model of continental North China. This model, denoted as IGP-NorthChina2022TG, contains 15 gravity field solutions determined using an innovative approach that relies on terrestrial gravity measurements and Slepian basis functions. IGP-NorthChina2022TG provides degree 150 gravity changes (spatial resolution of ~120 km) on a semi-annual basis from September 2009 to September 2016, in contrast to the monthly degree 60 GRACE solutions. Despite their different temporal resolutions, the good agreement between GRACE and the ground-based results up to degree 60 confirms the robustness and reliability of the proposed method and favors the combination of these two types of measurements. The gravity changes with much finer spatial resolution from IGP-NorthChina2022TG could complement GRACE solutions for sub-regional scale investigations in North China.

Abstract Background The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment. Methods Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC–MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth. Results Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing the dephosphorylation of β-catenin and leading to the accumulation of cytosolic phospho-β-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity. Conclusions Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Losses in surface irrigation include deep percolation and runoff, which is one of the ways to increase the efficiency of furrow irrigation, using a closed-end mode in irrigation systems. This research was conducted to evaluate the effects of geometrical variables (slope and length of furrow) and flow control (inflow rate and cut-off time) on application efficiency (AE) and the uniformity of water distribution in a closed-end furrow irrigation system. The length, slope, inflow rate, and cut-off time are considered as the decision-making variables for developing the multi-objective genetic algorithm based on the non-dominated sorting. For this purpose, three irrigation furrows with the closed-end system were considered. The optimization algorithm for calculating the objective functions involves maximizing the minimum water depth and minimizing the infiltration depth in a modeling loop. The optimization algorithm was linked to the WinSRFR software to calculate the objective functions. The results showed that the best combination of inflow rate and the cut-off time for 75 mm of required water depth was 1.9 L/s/m and 150 min, respectively, which increased AE and distribution uniformity to 79 and 78%. Furthermore, the AE in the closed-end furrow irrigation system is higher (30–50%) than the open-end method in different scenarios. HIGHLIGHTS The optimization model of the central force algorithm has been used to design the water distribution system in the farm.; The application of optimal design could increase the efficiency of irrigation adequacy and the uniformity of distribution.; The proposed modeling is a suitable tool for increasing crop production and water efficiency in agriculture.;

Abstract Background Perineural invasion (PNI) is regarded as a prognostic factor for patients with GC. However, the significance of PNI in patients with stage II GC remains unclear. This study aimed to investigate the clinical implication of PNI in patients with stage II GC undergoing curative resection. Methods Patients with stage II GC who underwent curative resection were retrospectively evaluated from January 2010 to July 2019. According to PNI status, all patients were divided into two groups: with or without PNI. The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. Results A total of 233 patients were included in this study. There were 100 patients with PNI (42.92%) and 133 patients without PNI (57.08%). The overall survival (OS) and disease-free survival (DFS) rates for patients with PNI were significantly lower than that for patients without PNI (p = 0.019 and p = 0.032, respectively). Multivariate analysis indicated that the presence of PNI was an independent risk factor for OS (hazard ratio (HR): 1.76, 95% confidence interval (CI) 1.02–3.06, p = 0.044) and DFS (HR: 1.70, 95% CI 1.04–2.80, p = 0.035), while adjuvant chemotherapy (AC) was an independent protective factor for OS (HR: 0.51, 95% CI 0.30–0.88, p = 0.016) and DFS (HR: 0.52, 95% CI 0.31–0.86, p = 0.011). Furthermore, among patients with PNI, those who received AC had better OS (p = 0.022) and DFS (p = 0.027) than their counterparts. When patients with PNI received AC, the OS (p = 0.603) and DFS (p = 0.745) appeared to be similar to those without PNI and no AC. Conclusion In patients with stage II GC undergoing curative resection, the presence of PNI was associated with worse survival, which appeared to improve with the treatment of AC, indicating a potential need for more intensive AC.

Abstract Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections.

Abstract Background Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. Methods In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians’ perspectives during the process of SDM, which was conducted before and after the CME course was provided. Results In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants’ age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). Conclusions Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician’s educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.

Passiflora edulis Sims (2n = 18) is a perennial plant with high utilization values, but its spontaneous polyploidy in nature has yet to be seen. Thus, this study aims to enhance our understanding of polyploidy P. edulis and provide rudimentary knowledge for breeding new cultivars. In this study, colchicine-induced tetraploid P. edulis (2n = 36) was used as experimental material (T1, T2, and T3) to explore the variances between it and its diploid counterpart in morphology, physiology, and biochemical characteristics, and a comparison of their performance under cold stress was conducted. We measured and collected data on phenotype parameters, chlorophyll contents, chlorophyll fluorescence, photosynthesis, osmotic substances, and antioxidant enzymes. The results showed that tetraploid P. edulis exhibited a shorter phenotype, more giant leaves, darker leaf color, and longer and fewer roots. Moreover, the physiological and biochemical analysis indicated that the tetraploid P. edulis had better photosynthesis systems and higher chlorophyll fluorescence parameters than the diploid P. edulis. Additionally, the tetraploid P. edulis had higher activity of antioxidant enzymes (SOD, POD, CAT) and lower MDA content to maintain better resistance in low temperatures. Overall, we conclude that there were apparent differences in the morphological, physiological, and biochemical traits of the tetraploid and diploid P. edulis. The tetraploid plants showed better photosynthesis systems, higher osmotic substance content, and antioxidant enzyme activity than the diploid, even under cold stress. Our results suggest that tetraploids with more abundant phenotype variation and better physiological and biochemical traits may be used as a new genetic germplasm resource for producing new P. edulis cultivars.

The expansion of Internet of Things (IoT) technology and the rapid increase in data in smart grid business scenarios have led to a need for more dynamic and adaptive security strategies. Traditional static security measures struggle to meet the evolving low-voltage security requirements of state grid systems under this new IoT-driven environment. By incorporating symmetry in metaheuristic algorithms, we can further improve performance and robustness. Symmetrical properties have the potential to lead to more efficient and balanced solutions, improving the overall stability of the grid. We propose a gnn-enhanced ant colony optimization method for orchestrating grid security strategies, which trains across combinatorial optimization problems (COPs) that are representative scenarios in the state grid business scenarios, to learn specific mappings from instances to their heuristic measures. The learned heuristic metrics are embedded into the ant colony optimization (ACO) to generate the optimal security policy adapted to the current security situation. Compared to the ACO and adaptive elite ACO, our method reduces the average time consumption of finding a path within a limited time in the capacitated vehicle routing problem by 67.09% and 66.98%, respectively. Additionally, ablation experiments verify the effectiveness and necessity of the individual functional modules.