Search

Abstract Background In China, Tongguanteng injection (TGT) is widely used in the treatment or adjuvant treatment of various types of cancer. However, the effect and mechanism of TGT in osteosarcoma is not clear. Methods The 143B and MG-63 cells were treated with different concentrations of TGT. Cell proliferation, migration, invasion and apoptosis were detected using CCK8 assay, transwell assay and flow cytometry. Differentially expressed genes (DEGs) were screened using RNA sequencing (RNA-seq). The identified mRNA and protein expression associated with the IRE1/CHOP pathway was validated by RT-PCR and western blot assay. To explore the underlying mechanisms, 4-phenylbutyric acid (4-PBA) was selected as a specific endoplasmic reticulum (ER) stress inhibitor. Small interfering RNA (siRNA) or pEX‐3-ERN1 plasmid was transfected into 143B cells to silence or overexpress IRE1, respectively. The potential downstream proteins, including CHOP, and apoptosis associated proteins, caspase-3 and PARP1 were determined. Furthermore, the effect of TGT was demonstrated in 143B cell tumor-bearing mice in vivo. H&E staining, TUNEL staining and immunohistochemistry were conducted in tumor tissues obtained from the xenograft mouse model. Results TGT was shown to dramatically suppress the proliferation, migration and invasion, and induce apoptosis of osteosarcoma 143B and MG-63 cells in vitro. The identified DEGs included HSPA5 (encoding BiP) and ERN1 (encoding the IRE1 protein), as well as apoptosis-associated gene DDIT3 (encoding the CHOP protein). The term “IRE1-mediated unfolded protein response” was screened to be the most enriched biological process GO term. The expression of ER stress-associated proteins including ATF6, BiP, p-IRE1, XBP1s and CHOP, as well as apoptosis-associated cleaved caspase-3 and cleaved PARP1 proteins, was significantly upregulated by TGT treatment in osteosarcoma 143B cells, suggesting that TGT might promote the apoptosis of osteosarcoma 143B cells through the IRE1/CHOP pathway. Furthermore, knocking down IRE1 with si-IRE1 or inhibiting of ER stress with 4-PBA suppressed the expression of ATF6, BiP, XBP1s and CHOP induced by TGT, as well as the expression of cleaved caspase-3 and cleaved PARP1. On the contrary, overexpressing IRE1 promoted CHOP expression and induced osteosarcoma cell apoptosis. Consistent with in vitro results, TGT dramatically inhibited the tumor growth and promoted the expression of p-IRE1 and CHOP in tumor-bearing mice. Conclusion The findings suggest that TGT exerts an anti-osteosarcoma effect in vitro and in vivo. The underlying mechanism might be associated with the activation of IRE1/CHOP pathway in ER stress. Our findings suggest that targeting IRE1/CHOP pathway might be a potential novel approach for osteosarcoma treatment.

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA—GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA—GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models’ predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA—GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA—GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

Abstract Background Individuals with sensory processing sensitivity (SPS) tend to be overreactive in response to negative environmental stimuli. More is known about the positive relationship between SPS and quality of life (QoL); nevertheless, less is known regarding the roles of resilience and social determinants in this association. This research aimed to investigate the potential mediation effect of resilience and the moderation effect of social determinants on the relationship between SPS and QoL in a large sample of Chinese cancer patients. Methods We used the most recent datasets from an ongoing project conducted in southwest China. A two-stage random sampling strategy with a probability proportionate to sample size (PPS) design was adopted. The associations between resilience, SPS, and QoL were evaluated using a linear regression model. Path analysis was adopted to examine the mediation of resilience. Results Resilience was positively associated with quality of life, while increased sensory processing sensitivity was negatively associated with quality of life. The restricted cubic spline analysis revealed that as resilience increased, the coefficients of quality of life rapidly increased across all domains. Conversely, the coefficients for quality of life gradually decreased with the escalation of sensory processing sensitivity. Resilience was a significant mediator, accounting for 21.88% of the total SPS-QoL association. The mediation effect of resilience varied across ethnicity and sex. Conclusion Sensory processing sensitivity was significantly associated with quality of life in cancer patients, and promoting resilience could mitigate this negative impact. However, the effect of resilience varies across sex and ethnicity. Therefore, targeted resilience promotion interventions, especially those integrating social characteristics, should be considered for implementation.

Abstract Background Evidence on the prevalence of smoking in China remains insufficient, with most previous studies focusing on a single region. However, smoking prevalence exhibits significant inequalities across the entire country. This study aimed to evaluate the risk of tobacco prevalence across the country, taking into account spatial inequalities. Methods The data used in this study were collected in 23 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in 2022. Large population survey data were used, and a Bayesian geostatistical model was employed to investigate smoking prevalence rates across multiple spatial domains. Findings Significant spatial variations were observed in smokers and exposure to secondhand smoke across China. Higher levels of smokers and secondhand smoke exposure were observed in western and northeastern regions. Additionally, the autonomous region of Tibet, Shanghai municipality, and Yunnan province had the highest prevalence of smokers, while Tibet, Qinghai province, and Yunnan province had the highest prevalence of exposure to secondhand smoke. Conclusion We have developed a model-based, high-resolution nationwide assessment of smoking risks and employed rigorous Bayesian geostatistical models to help visualize smoking prevalence predictions. These prediction maps provide estimates of the geographical distribution of smoking, which will serve as strong evidence for the formulation and implementation of smoking cessation policies. Highlights Our study investigated the prevalence of smokers and exposure to secondhand smoke in different spatial areas of China and explored various factors influencing the smoking prevalence. For the first time, our study applied Bayesian geostatistical modeling to generate a risk prediction map of smoking prevalence, which provides a more intuitive and clear understanding of the spatial disparities in smoking prevalence across different geographical regions, economic levels, and development status. We found significant spatial variations in smokers and secondhand smoke exposure in China, with higher rates in the western and northeastern regions.

Abstract The relationship between blood urea nitrogen to albumin ratio (BAR) and the prognosis of patients with tuberculosis (TB) complicated by sepsis remains unclear. This study aimed to explore the association between BAR and overall patient prognosis. This was a retrospective cohort study of patients with TB complicated by sepsis who were admitted to the intensive care unit (ICU) of the Public Health Clinical Center of Chengdu between January 2019 and February 2023. The relationship between BAR values and prognosis in these patients was investigated using multivariate Cox regression, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis. Sensitivity analyses were conducted to assess the robustness of the results. Our study included 537 TB patients complicated by sepsis admitted in the ICU, with a median age of 63.0 (48.0, 72.0) years; 76.7% of whom were men. The multivariate-restricted cubic spline analysis showed a non-linear association between BAR and patient prognosis. In the threshold analysis, we found that TB patients complicated by sepsis and a BAR

Objective To screen the risk factors of hydrocephalus after decompressive craniectomy in patients with cerebral hernia after traumatic brain injury (TBI), and construct a Bayesian network model based on the risk factors. Methods A total of 77 patients with cerebral hernia after TBI who underwent decompressive craniotomy in Nanjing Tongren Hospital Affiliated to Southeast University from March 2020 to January 2022 were included. They were divided into hydrocephalus group (n = 25) and non - hydrocephalus group (n = 52) according to whether hydrocephalus was complicated after surgery. The risk factors of hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI were analyzed by univariate and multivariate Logistic regression analyses. The Bayesian network model was constructed based on the risk factors, and the receiver operating characteristic (ROC) curve and calibration curve were drawn and Hosmer-Lemeshow goodness-of-fit test was conducted. Results In hydrocephalus group, the Glasgow Coma Scale (GCS) score at admission (t = 2.178, P = 0.032), the ratio of cerebrospinal fluid replacement after lumbar puncture (χ2 = 8.675, P = 0.003), and the level of β2 -microglobulin after operation (t = 11.146, P = 0.000) were lower than those in non-hydrocephalus group, while subarachnoid hemorrhage (χ2 = 5.901, P = 0.015), bilateral operation (χ2 = 6.441, P = 0.011), the ratio of dural unstitched during operation (χ2 = 9.759, P = 0.002), postoperative intraventricular hemorrhage (χ2 = 8.938, P = 0.003), postoperative midline displacement > 10 mm (χ2 = 7.589, P = 0.006), and intracranial infection (χ2 = 4.519, P = 0.034), as well as postoperative coma time (t = 2.709, P = 0.008) were higher than those in non - hydrocephalus group. Logistic regression analysis showed that subarachnoid hemorrhage (OR = 1.885, 95%CI: 1.432-2.240; P = 0.012), dural unstitched during operation (OR = 1.468, 95%CI: 1.215-1.930; P = 0.006), long postoperative coma time (OR = 1.574, 95%CI: 1.358-1.926; P = 0.007), postoperative intraventricular hemorrhage (OR = 1.550, 95%CI: 1.254-1.768; P = 0.010), the level of β2- microglobulin increased after operation (OR = 1.622, 95%CI: 1.165-1.840; P = 0.004) were risk factors for hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI. Based on these 5 factors, the Bayesian network model was constructed, and the area under ROC curve was 0.886 (95%CI: 0.823-0.925, P = 0.000). The calibration curve showed that there was a good consistency between the predicted probability and the actual probability, while the Hosmer-Lemeshow goodness-of-fit test showed no significant difference (χ2 = 8.760, P = 0.232), which indicated that the model had good discrimination, calibration and accuracy. Conclusions Subarachnoid hemorrhage, dural unstitched during operation, long postoperative coma time, postoperative intra ventricular hemorrhage, and elevated β2 - microglobulin level are the risk factors for hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI.

Introduction: Previous studies have suggested a potential correlation between psoriasis (PS) and ulcerative colitis (UC). However, studies exploring the shared mechanisms of both diseases remain limited. Current treatments primarily involve using immunosuppressive drugs, which can lead to potential side effects and drug resistance. Traditional Chinese medicine has demonstrated favorable efficacy in treating UC and PS with fewer side effects. This study aims to elucidate the shared biological mechanisms underlying UC and PS and to predict natural compounds effective for treating both disorders. Method: We collected and validated differentially expressed genes associated with UC and PS from the Gene Expression Omnibus database. A protein-protein interaction network was constructed using the STRING database, aiding in identifying core targets. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were utilized to analyze the functions and genomic enrichment of the identified core targets. The CIBERSORT method was employed to assess the correlation of core targets with immune cells. Compounds with potential therapeutic values were selected from the Coremine and TCMSP databases, and their therapeutic efficacy was predicted via molecular docking. Results: In UC and PS, 20 common core targets were identified, with matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 1 (MMP1), cluster of differentiation 274 (CD274), C-X-C motif chemokine ligand 10 (CXCL10), and topoisomerase II alpha (TOP2A) emerging as the most relevant targets shared between both conditions. Elevated levels of macrophages and dendritic cells were observed in UC and PS, with CXCL10 exhibiting the closest association with macrophages. UC and PS shared common signaling pathways, including IL-17, TNF, and chemokine signaling pathways, among others. Molecular docking revealed that quercetin, baicalen, irisolidone, rutaecarpine, epigallocatechin-3-gallate, and others held potential as natural compounds for treating both disorders. Conclusion: MMP9, MMP1, and CXCL10, central mediators in the inflammatory pathways of UC and PS, establish a shared mechanism by triggering cytokine and chemokine activation, leading to tissue damage and positioning them as promising therapeutic targets for both conditions. Compounds such as quercetin, luteolin, irisolidone, rutaecarpine, and so on may be key drugs for treating both conditions. These findings suggest the potential advancement of therapeutic strategies and the enhancement of patient care by exploring shared mechanisms and predicting promising natural compounds for treating UC and PS.

The treatment time window for acute cerebral infarction in global guidelines is within 24 h. We report a patient who was admitted to the hospital and underwent endovascular treatment reaching 40 h. During vascular examination, the thrombus moved to distant segment, and then the surgeon quickly performed endovascular treatment. The patient ultimately achieved a good outcome. This case indicates that thrombus is moveable at any time, we expected to provide advice to clinical doctors that vascular examination should also be arranged as soon as possible to clarify the etiology in stroke patients especially with low NIHSS scores.

Depression is a common cause of human disability and death. Some patients are not sensitive to antidepressants, and also the recurrence rate is very high. Unfortunately, there are many problems with existing antidepressants. So, it is urgent to find a new antidepressant aiming at multiple targets. Recently, researchers have found that soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is closely related to the progression of depression. This review discusses the potential mechanisms of the SNARE complex in glial cells, and hopes to contribute to the understanding of depression and provide new ideas for clinical development of novel antidepressant drugs.

Abstract Background There may be unexplored interactions between family health, personality, and smoking that could help provide new perspectives on tobacco control. Objective To examine the relationship between the health of one’s family and their smoking habits, as well as investigate the potential influence of personality on this relationship. Methods For this cross-sectional investigation, a national survey conducted in China in 2022 recruited a total of 21,916 individuals. The Family Health Scale was utilized to assess the health of the family. The 10-item Big Five Inventory scale was utilized to assess the Big five personality traits. The relationship between big five personality, family health, and smoking were investigated using binary and linear logistic regression. The indirect effects mediated by Big five personality were analyzed using mediation analysis with Sobel tests, and the indirect effects were composited using the Karlson-Holm-Breen method. Results The overall prevalence of smoking in the study population was 14.87%, 26.19% for males and 3.54% for females. Urban and rural smoking prevalence was 13.81% and 16.10% respectively. Binary logistic regression analysis revealed a significant negative relationship between smoking and family health (odds ratio 0.964, 95% CI 0.959, 0.970, P

Fieldbus transmitters are commonly used in modern industrial productions, particularly in Safety Instrumented Systems (SIS). Safety and security are critical considerations in the design and operation of these transmitters. Previous research has tended to address safety issues and security issues separately, but with the increasing complexity of network technology, it is important to analyze them simultaneously. In this paper, a systematic framework for comprehensively analyzing random failures and cyber-attack failures is proposed. The framework adopts the FMEA-IMEA method, which combines Failure Modes and Effects Analysis (FMEA) and Intrusion Modes and Effects Analysis (IMEA), to analyze failure modes and effects of fieldbus transmitters. In addition, by extending Reliability Block Diagrams (RBD), the impact of random failures and cyber-attack failures on fieldbus transmitters is quantitatively determined. At the same time, calculation approach of the residual error rate (RER), Component counting method, and Monte Carlo are used to determine random failure rate and cyber-attack failure rate. Using fieldbus pressure transmitter and fieldbus temperature transmitter as examples, the results demonstrate that security issues can significantly impact the safety integrity level. In fact, the safety integrity level is reduced from SIL3 to SIL1 when cyber-attacks are considered. Compared to existing FMEA, the proposed approach offers a more comprehensive analysis of random failures and cyber-attack failures in fieldbus transmitters.

The plague, caused by Yersinia pestis, is a natural focal disease and the presence of Y. pestis in the environment is a critical ecological concern worldwide. The role of Y. pestis phages in the ecological life cycle of the plague is crucial. Previously, a temperature-sensitive phage named vB_YpM_HQ103 was isolated from plague foci in Yunnan province, China. Upon infecting the EV76 strain of Y. pestis, vB_YpM_HQ103 exhibits lysogenic behavior at 21 °C and lytic behavior at 37 °C. Various methods including continuous passage lysogenic tests, in vitro lysis tests, comparative genomic assays, fluorescence quantitative PCR and receptor identification tests were employed to demonstrate that the lysogenic life cycle of this phage is applicable to wild Y. pestis strains; its lysogeny is pseudolysogenic (carrying but not integrating), allowing it to replicate and proliferate within Y. pestis. Furthermore, we have identified the outer membrane protein OmpA of Y. pestis as the receptor for phage infection. In conclusion, our research provides insight into the characteristics and receptors of a novel Y. pestis phage infection with a pseudolysogenic cycle. The findings of this study enhance our understanding of Y. pestis phages and plague microecology, offering valuable insights for future studies on the conservation and genetic evolution of Y. pestis in nature.

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer’s disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood–brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid β (Aβ) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.

Objective: This study aimed to develop a universally applicable, feedback-informed Self-Excitation Attention Residual Network (SEAR) model. This model dynamically adapts to evolving disease trends and surveillance system changes, accommodating various scenarios. Thereby enhancing the effectiveness of early warning systems. Methods: Surveillance data on influenza-like illness (ILI) was collected from various regions including Northern China, Southern China, Beijing, and Yunnan. The reproduction number (Rt) was estimated to determine the threshold for issuing warnings. The Self-Excitation Attention Residual Network (SEAR) was devised employing deep learning algorithms and was trained, validated, and tested. The SEAR model's efficacy was assessed based on five metrics: accuracy rate, recall rate, F1 score, confusion matrix, and the receiver operating characteristic curve. Results: With an advance warning set at three days, the SEAR model outperformed five primary models − logistic regression, support vector machine, random forest, Extreme Gradient Boosting, and Long Short-Term Memory model − in all five evaluation metrics. Notably, the model's warning performance declined with an increase in the early warning value and the number of warning days, albeit maintaining a ROC value over 0.7 in all scenarios. Conclusion: The SEAR model demonstrated robust early warning performance for influenza in diverse Chinese regions with high accuracy and specificity. This novel model, augmenting traditional systems, supports widespread application for respiratory disease outbreak monitoring. Future evaluations could incorporate alternative indicators, with the model continuously updating through data feedback, thus enhancing its universal applicability. Ongoing optimization, using iterative feedback and expert judgment, heralds a transformative approach to surveillance-based early warning strategies.

BackgroundChronic spontaneous urticaria (CSU) is a common chronic inflammatory skin disease that manifests as itching and wheals, seriously affecting quality of life. Clinical observations and previous research trials have shown that acupuncture is safe and effective for the treatment of CSU. However, there are problems, such as a short duration of action and frequent treatment. Compared with traditional acupuncture, acupoint catgut embedding (ACE) has the advantages of a longer effect and higher compliance. Clinical trials are needed to prove its efficacy and mechanism of action. ObjectiveThis trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. MethodsThis is a randomized, double-blind, placebo-controlled trial. In this trial, 108 participants aged 18-60 years with a diagnosis of CSU and no history of ACE will be randomly assigned to 2 groups (1:1 ratio) using the Statistical Analysis System: treatment (ACE) and control (sham ACE). The participants and efficacy evaluators will be blinded to the grouping. Both the ACE and sham ACE groups will undergo acupuncture, but the sham ACE group will not receive catgut sutures. Treatment will be performed twice weekly for 8 weeks, with a 1-week run-in period and a 16-week follow-up period. Twenty patients will be randomly selected to undergo functional magnetic resonance imaging before and after the treatment period. The primary outcome will be the urticaria activity score over 7 days (UAS7). We will use R (version 4.0.1; R Project for Statistical Computing) to perform ANOVA and independent samples t tests to compare the differences within and between groups before and after treatment by judging the rejection range based on a significance level of .05. ResultsThe study protocol has been approved by the Ethics Committee of Guang’anmen Hospital on September 7, 2022, and has been registered on November 30, 2022. Recruitment began on March 1, 2023. A total of 4-6 participants are expected to be recruited each month. The recruitment is planned to be completed on March 1, 2025, and we expect to publish our results by the winter of 2025. As of November 1, 2023, we have enrolled 25 participants with CSU. ConclusionsThis randomized, double-blind, placebo-controlled trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. We hypothesize that wheals and itching will show greater improvement in participants receiving active therapy than in those receiving sham treatment. The limitations of this study include its single-center trial design, small sample size, and short treatment duration, which may have certain impacts on the research results. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200066274; https://www.chictr.org.cn/showprojEN.html?proj=179056 International Registered Report Identifier (IRRID)DERR1-10.2196/54376

Key Clinical Message One Kirsten Ras (KRAS) G12C mutated non‐small cell lung cancer (NSCLC) patient had improved poor performance status and obtained mixed response with the first‐line KRAS‐targeted treatment of sotorasib. After disease progression, partial response was achieved with chemotherapy plus immunotherapy. KRAS G12C mutated immunoenvironment in NSCLC may favor the immunotherapy. Abstract KRAS is one of the most commonly mutated genes, which used to be untargetable. The phase II CodeBreak 100 trial revealed 6.8‐month median progress‐free survival (PFS) and 12.5‐month overall survival (OS) in previously treated KRAS G12C‐mutant NSCLC patients treated with KRAS inhibitor, sotorasib. The specimens of the brain, lymph node (LN), and blood from the patient were analyzed by next‐generation sequencing. Hematoxylin and eosin staining and immunohistochemistry were performed for pathological characterization. Computed tomography (CT) and magnetic resonance imaging (MRI) scan were used for treatment response evaluation. The patient was diagnosed in a bad Eastern Cooperative Oncology Group performance status (ECOG‐PS) with metastatic KRAS G12C‐mutated lung adenocarcinoma who had achieved mixed response to sotorasib as the first‐line treatment. Although 5‐month PFS of the treatment with sotorasib was not surprising, the patient achieved significantly improved ECOG‐PS score from 4 to 1. Subsequently, partial response (PR) was achieved with the treatment of pemetrexed plus pembrolizumab. This case highlights superior efficacy of first‐line treatment with sotorasib for the advance untreated KRAS G12C‐mutant patients. The high efficacy of the treatment with chemotherapy plus immunotherapy revealed that immunoenvironment of KRAS G12C‐mutated patient may favor the immunotherapy.

Abstract Copper‐based bimetallic heterojunction catalysts facilitate the deep electrochemical reduction of CO2 (eCO2RR) to produce high‐value‐added organic compounds, which hold significant promise. Understanding the influence of copper interactions with other metals on the adsorption strength of various intermediates is crucial as it directly impacts the reaction selectivity. In this review, an overview of the formation mechanism of various catalytic products in eCO2RR is provided and highlight the uniqueness of copper‐based catalysts. By considering the different metals' adsorption tendencies toward various reaction intermediates, metals are classified, including copper, into four categories. The significance and advantages of constructing bimetallic heterojunction catalysts are then discussed and delve into the research findings and current development status of different types of copper‐based bimetallic heterojunction catalysts. Finally, insights are offered into the design strategies for future high‐performance electrocatalysts, aiming to contribute to the development of eCO2RR to multi‐carbon fuels with high selectivity.

BackgroundCircular RNAs (circRNAs) play an important role in the occurrence and development of diseases. However, the role of circRNAs in male smokers with chronic obstructive pulmonary disease (COPD) remains unclear.MethodsStable COPD patients and healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were extracted. After high-throughput RNA sequencing (RNA-Seq) of PBMCs, a bioinformatics method was used to analyse differentially expressed (DE) circRNAs (DEcircRNAs) and mRNAs (DEmRNAs).ResultsTotal of 114 DEcircRNAs and 58 DEmRNAs were identified. Functional enrichment analysis showed that processes related to COPD include the regulation of interleukin (IL)-18, IL-5 and the NLRP3 inflammasome; differentiation of T helper type 1 (Th1), Th2, and Th17 cells, and the AMPK, Wnt, JAK-STAT, and PI3K-Akt signalling pathways. In the protein–protein interaction (PPI) network, the core genes were MYO16, MYL4, SCN4A, NRCAM, HMCN1, MYOM2, and IQSEC3. Small-molecule prediction results revealed potential drugs for the COPD treatment. Additionally, the circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network was constructed.ConclusionThis study identified a set of dysregulated circRNAs and mRNAs and revealed potentially important genes, pathways, new small-molecule drugs and ceRNA regulatory networks in male smokers with COPD. These circRNAs might be prospective biomarkers or potential molecular targets of the ceRNA mechanism for COPD.

As ancient organisms, tree ferns play a crucial role as an evolutionary bridge between lower and higher plant species, providing various utilitarian benefits. However, they face challenges such as overexploitation, climate change, adverse environmental conditions, and insect pests, resulting in conservation concerns. In this study, we provide an overview of metabolic and transcriptomic resources of leaves in two typical tree ferns, A. spinulosa and A. metteniana, and explore the resistance genes for the first time. The landscape of metabolome showed that the compound skimmin may hold medicinal significance. A total of 111 differentially accumulated metabolites (DAMs) were detected, with pathway enrichment analysis highlighting 14 significantly enriched pathways, including 2-oxocarboxylic acid metabolism possibly associated with environmental adaptations. A total of 14,639 differentially expressed genes (DEGs) were found, among which 606 were resistance (R) genes. We identified BAM1 as a significantly differentially expressed R gene, which is one of the core genes within the R gene interaction network. Both the maximum-likelihood phylogenetic tree and the PPI network revealed a close relationship between BAM1, FLS2, and TMK. Moreover, BAM1 showed a significant positive correlation with neochlorogenic acid and kaempferol-7-O-glucoside. These metabolites, known for their antioxidant and anti-inflammatory properties, likely play a crucial role in the defense response of tree ferns. This research provides valuable insights into the metabolic and transcriptomic differences between A. spinulosa and A. metteniana, enhancing our understanding of resistance genes in tree ferns.

Abstract Emergent plants have been remarkably effective in reducing phosphorus (P) discharge from ecological ditches; however, the treatment and recycling of these residues is a great challenge. In this study, magnetic biochars (MBs, i.e., MB-A, MB-C, and MB-T) were fabricated from three emergent plant residues (Acorus calamus L., Canna indica L., and Thalia dealbata Fraser, respectively) and modified with Fe(II)/Fe(III). Scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction spectra confirmed the successful loading of Fe3O4 and FeO(OH) onto the surfaces of the MBs. Batch adsorption experiments showed that MBs exhibited a higher P adsorption capacity than that of the raw biochars. Within the range of 0.8–43.0 mg L−1 in solution, the adsorption capacities of P by MB-A, MB-C, and MB-T were 304.6–5658.8, 314.9–6845.6, and 292.8–5590.0 mg kg−1, with adsorption efficiencies of 95.2–32.9%, 98.4–39.8%, and 91.5–32.5%, respectively. The primary mechanisms that caused P to adsorb onto the MBs were inner-sphere complexation and electrostatic attraction. Low pH conditions were more beneficial for the P adsorption of the MBs, while co-existing anions had a negative impact with the following order: HCO3 − > SO4 2− > Cl−≈NO3 −. The P-31 nuclear magnetic resonance results further demonstrated that the main adsorbed P species on the MBs was orthophosphate, followed by orthophosphate monoesters and DNA. Overall, MBs offer a resource utilization strategy for emergent plant residues and P-laden MBs are promising alternative P fertilizers. Graphical Abstract

Hollow urchin-like substrates have been widely interested in the field of surface-enhanced Raman scattering (SERS) and photocatalysis. However, most reported studies are simple nanoscale urchin-like substrate with limited light trapping range and complicated preparation process. In this paper, a simple and effective controllable synthesis strategy based on micro-nano hierarchical urchin-like ZnO/Ag hollow spheres was prepared. Compared with the 2D structure and solid spheres, the 3D urchin-like ZnO/Ag hollow sphere has higher laser utilization and more exposed specific surface area due to its special hollow structure, which resulted in excellent SERS and photocatalytic performance, and successfully realize the detection and photodegradation of antibiotics. The limited of detection of metronidazole can reach as low as 10−9 M, and degradation rate achieve 89 % within 120 min. The experimental and theoretical results confirm that the ZnO/Ag hollow spheres can be used in the development of ZnO heterostructure for the detection and degradation of antibiotics, which open new avenues for the development of novel ZnO-based substrate in SERS sensing and catalytic application to address environmental challenges.

Abstract Oxidative stress is an imbalance between the body’s reactive oxygen species and antioxidant defense mechanisms. Oxidative stress is involved in the development of several cardiovascular diseases, such as pulmonary hypertension, atherosclerosis, and diabetes mellitus. A growing number of studies have suggested the potential role of oxidative stress in the pathogenesis of pulmonary embolism. Biomarkers of oxidative stress in pulmonary embolism have also been explored, such as matrix metalloproteinases, asymmetric dimethylarginine, and neutrophil/lymphocyte ratio. Here, we comprehensively summarize some oxidative stress mechanisms and biomarkers in the development of acute pulmonary embolism and summarize related treatments based on antioxidant stress to explore effective treatment strategies for acute pulmonary embolism.

Abstract Hyoscyamine and scopolamine (HS), two valuable tropane alkaloids of significant medicinal importance, are found in multiple distantly related lineages within the Solanaceae family. Here we sequence the genomes of three representative species that produce HS from these lineages, and one species that does not produce HS. Our analysis reveals a shared biosynthetic pathway responsible for HS production in the three HS-producing species. We observe a high level of gene collinearity related to HS synthesis across the family in both types of species. By introducing gain-of-function and loss-of-function mutations at key sites, we confirm the reduced/lost or re-activated functions of critical genes involved in HS synthesis in both types of species, respectively. These findings indicate independent and repeated losses of the HS biosynthesis pathway since its origin in the ancestral lineage. Our results hold promise for potential future applications in the artificial engineering of HS biosynthesis in Solanaceae crops.

Abstract This study aimed to evaluate the guiding role of left adrenal vein (LAV) for right adrenal venous sampling (AVS). A total of 347 patients who were diagnosed with primary aldosteronism (PA) and underwent successful AVS procedures from January 2020 to July 2021 were retrospectively analyzed. According to the different quadrant position of the orifice of right adrenal vein (RAV), the area where the orifice of RAV is located is divided into three areas: A, B, and C and the area A is further subdivided into A1, A2, and A3 areas. By counting the area where the orifice of RAV is located, the guiding role of the LAV on the RAV is determined. Most of the orifice of RAV are located in area A, and the proportions of areas A, B, and C was 96.8%, 1.4%, and 1.7%, respectively. In area A, areas A1, A2, and A3 account for 80.9%, 17.0%, and 2.1%, respectively. High body mass index, female and smaller the angle between the LAV and horizontal line was associated with the closer positional relationship between the LAV on the RAV. These findings suggest that most of the horizontal position of the RAV orifice is close to the horizontal position of the most distal end of the LAV, which indicate that the LAV location can play an important role on the guiding for right AVS. Additionally, body mass index, sex, and the angle of the LAV was largely related to location of the orifice of the RAV.

Camellia luteoflora is a rare and endangered plant endemic to China. It has high ornamental and potential economic and medicinal value, and is an important germplasm resource of Camellia. To understand the distributions and differences in metabolites from different parts of C. luteoflora, in this study, we used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to examine the types and contents of chemical constituents in five organs of C. luteoflora: roots, stems, leaves, flowers, and fruits. The results showed that a total of 815 metabolites were identified in the five organs and were classified into 18 main categories, including terpenoids (17.1%), amino acids (10.4%), flavonoids (10.3%), sugars and alcohols (9.8%), organic acids (9.0%), lipids (7.1%), polyphenols (4.8%), alkaloids (4.8%), etc. A total of 684 differentially expressed metabolites (DEMs) in five organs were obtained and annotated into 217 KEGG metabolic pathways, among which metabolic pathways, ABC transporters, the biosynthesis of cofactors, and the biosynthesis of amino acids were significantly enriched. In DEMs, flowers are rich in flavonoids, polyphenols, organic acids, and steroids; fruits are rich in amino acids, alkaloids, vitamins, and xanthones; stems are rich in lignans; and leaves have the highest relative content of phenylpropanoids, ketoaldehydic acids, quinones, sugars and alcohols, terpenoids, coumarins, lipids, and others; meanwhile, the metabolite content is lower in roots. Among the dominant DEMs, 58 were in roots, including arachidonic acid, lucidone, isoliquiritigenin, etc.; 75 were in flowers, including mannose, shikimic acid, d-gluconic acid, kaempferol, etc.; 45 were in the fruit, including pterostilbene, l-ascorbic acid, riboflavin, etc.; 27 were in the stems, including salicylic acid, d-(-)-quinic acid, mannitol, (-)-catechin gallate, etc.; there was a maximum number of 119 dominant metabolites in the leaves, including oleanolic acid, l-glucose, d-arabitol, eugenol, etc. In sum, the rich chemical composition of C. luteoflora and the significant differences in the relative contents of metabolites in different organs will provide theoretical references for the study of tea, flower tea, edible oil, nutraceuticals, and the medicinal components of C. luteoflora.

The effects of different contents of e-waste alloy on the microstructure and joint properties of Cu90PSn brazing filler metal was investigated during copper and copper brazing. Microstructure of base metal and brazing filler metal was studied with scanning electronic microscopy (SEM). The properties of brazing joint obtained by adding different electronic waste filler metal for smelting copper alloy were compared together. The results indicated that the fluidity of Cu90PSn brazing filler metal was weakened and the spreading property of Cu90PSn brazing filler metal was damaged after the addition of e-waste copper alloy. The structure of Cu90PSn brazing filler metal is mainly composed of (Cu), Cu3P and (Cu,Sn) compounds. When a small amount of electronic waste copper alloy is added, a trace amount of Fe in the brazing filler metal is distributed in the matrix structure of the filler metal in the form of solid solution. With the increase of copper alloys contents by smelting e-waste, Fe content in Cu90PSn brazing filler metal increases; the granular Fe3P phosphide changes into lamellar form. The Cu3P compound phase changes from continuous large orderly arrangement to discontinuous small block structure. Therefore, adding a trace amount of electronic waste copper alloy to the solder induction brazing copper/copper can obtain a uniform composition of the brazing structure. And the welding performance is not affected. However, As the content of e-waste smelted copper alloy continues to increase, the tensile strength shows a downward trend, which is attributed to the presence of brittle compound Fe3P in the joint.

Abstract Background Common air pollutants such as ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter play significant roles as influential factors in influenza-like illness (ILI). However, evidence regarding the impact of O3 on influenza transmissibility in multi-subtropical regions is limited, and our understanding of the effects of O3 on influenza transmissibility in temperate regions remain unknown. Methods We studied the transmissibility of influenza in eight provinces across both temperate and subtropical regions in China based on 2013 to 2018 provincial-level surveillance data on influenza-like illness (ILI) incidence and viral activity. We estimated influenza transmissibility by using the instantaneous reproduction number ( $${R}_{t}$$ R t ) and examined the relationships between transmissibility and daily O3 concentrations, air temperature, humidity, and school holidays. We developed a multivariable regression model for $${R}_{t}$$ R t to quantify the contribution of O3 to variations in transmissibility. Results Our findings revealed a significant association between O3 and influenza transmissibility. In Beijing, Tianjin, Shanghai and Jiangsu, the association exhibited a U-shaped trend. In Liaoning, Gansu, Hunan, and Guangdong, the association was L-shaped. When aggregating data across all eight provinces, a U-shaped association was emerged. O3 was able to accounted for up to 13% of the variance in $${R}_{t}$$ R t . O3 plus other environmental drivers including mean daily temperature, relative humidity, absolute humidity, and school holidays explained up to 20% of the variance in $${R}_{t}$$ R t . Conclusions O3 was a significant driver of influenza transmissibility, and the association between O3 and influenza transmissibility tended to display a U-shaped pattern.

Abstract Background COVID-19 pandemic emerged worldwide at the end of 2019, causing a severe global public health threat, and smoking is closely related to COVID-19. Previous studies have reported changes in smoking behavior and influencing factors during the COVID-19 period, but none of them explored the main influencing factor and high-risk populations for smoking behavior during this period. Methods We conducted a nationwide survey and obtained 21,916 valid data. Logistic regression was used to examine the relationships between each potential influencing factor (sociodemographic characteristics, perceived social support, depression, anxiety, and self-efficacy) and smoking outcomes. Then, variables related to smoking behavior were included based on the results of the multiple logistic regression, and the classification and regression tree (CART) method was used to determine the high-risk population for increased smoking behavior during COVID-19 and the most profound influencing factors on smoking increase. Finally, we used accuracy to evaluated the performance of the tree. Results The strongest predictor of smoking behavior during the COVID-19 period is acceptance degree of passive smoking. The subgroup with a high acceptation degree of passive smoking, have no smokers smoked around, and a length of smoking of ≥ 30 years is identified as the highest smoking risk (34%). The accuracy of classification and regression tree is 87%. Conclusion The main influencing factor is acceptance degree of passive smoking. More knowledge about the harm of secondhand smoke should be promoted. For high-risk population who smoke, the “mask protection” effect during the COVID-19 pandemic should be fully utilized to encourage smoking cessation.

Abstract Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks.

Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in various physiological and pathological processes as non-coding RNAs. However, circRNAs have recently garnered considerable attention due to their ability to be translated into peptides/proteins via internal ribosome entry site- or N6-methyladenosine-mediated pathways or rolling translation mechanisms. Furthermore, dysregulation of translatable circRNAs and their encoded proteins has been associated with developing and progressing diseases such as cancer. This review aims to summarize the driving mechanisms of circRNA translation and the available strategies in circRNA translation research. The main focus is on the emerging biological functions of translatable circRNAs, their regulatory mechanisms, and potential clinical applications in human diseases to provide new perspectives on disease diagnosis, prognosis, and targeted therapy.

Due to their excellent light transmission, heat resistance, corrosion resistance, high mechanical strength, and other characteristics, transparent materials have been widely used in emerging industries such as aviation, aerospace, microelectronics, interconnected communication, etc. Compared with the traditional mechanical processing and chemical processing of transparent materials, laser processing, with such characteristics as a high peak power, high energy density, and non-contact processing, has a lot of obvious advantages in processing efficiency and accuracy. In this paper, some of the recent research advancements concerning the laser processing of transparent materials are introduced in detail. Firstly, the basic mechanism of the interaction between the laser and material is briefly summarized on the time scale. The differences in principle between nanosecond, picosecond, and femtosecond pulse laser processing are analyzed. Then, the main technical means of the nanosecond laser processing of transparent materials are summarized. Next, the main application directions of the ultrafast laser processing of transparent materials are discussed, including the preparation of optical waveguide devices, periodic structure devices, micropores, and microchannels. Finally, this paper summarizes the prospects for the future development of laser processing transparent materials.

Pulmonary hypertension (PH) is a persistently progressive, incurable, multifactorial associated fatal pulmonary vascular disease characterized by pulmonary vascular remodeling. Long noncoding RNAs (lncRNAs) are involved in regulating pathological processes such as pulmonary vasoconstriction, thickening, remodeling, and inflammatory cell infiltration in PH by acting on different cell types. Because of their differential expression in PH patients, as demonstrated by the observation that some lncRNAs are significantly upregulated while others are significantly downregulated in PH patients, lncRNAs are potentially useful biomarkers for assessing disease progression and diagnosis or prognosis in PH patients. This article provides an overview of the different mechanisms by which lncRNAs are involved in the pathogenesis of PH.

To improve the compatibility of natural rubber (NR) and ethylene-propylene-diene terpolymer (EPDM) and enhance the resistance of NR/EPDM blends to hot air aging, radiation-vulcanized NR/EPDM blends were prepared by γ-ray radiation. The effects of blend ratio and radiation vulcanization on the mechanical properties of the blends were investigated by using a uniaxial tensile test. With increasing EPDM content, the tensile strength and elongation at break of the hot-vulcanized sample first decreased and then increased due to the poor compatibility between NR and EPDM. In addition, the mechanical properties of the radiation-vulcanized sample degraded with increasing blend ratio of EPDM. The irradiation treatment improved the initial mechanical properties of the NR/EPDM rubber, and radiation crosslinking enhanced the coupling structure between the NR and EPDM polymer. Following aging treatment in hot air, the mechanical properties of the radiation-vulcanized sample were found to be less degraded than those of the hot-vulcanized one. This proved that the introduction of radiation technology via thermal crosslinking improved the elongation retention rate of the radiative crosslinked sample after thermal aging. In particular, the change rate of elongation at break of the radiation sample was reduced by ~50% when the blend ratio of the NR was greater than that of EPDM. The results showed that the NR/EPDM blends prepared by radiation vulcanization had greater resistance to hot air aging than those prepared by hot vulcanization.

Abstract Background Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. Methods A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1 $$\alpha$$ α . Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. Results ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1 $$\alpha$$ α degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice’s median survival. Conclusions Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1 $$\alpha$$ α /VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.

Abstract Objective The causal association between osteoarthritis (OA) and bladder cancer remains unclear. This Mendelian randomization (MR) study was carried out to assess the potential causal effects of any OA, knee OA and hip OA, and bladder cancer. Method Genome‐wide association study (GWAS) summary data for OA and bladder cancer were obtained in GWAS CATALOG, UK Biobank, and FinnGen Consortium. Inverse‐variance weighted (IVW) approach was primarily conducted to evaluate the causal relationships between OA and bladder cancer, and MR‐Egger intercept and Cochran's Q test were mainly used to estimate heterogeneity and pleiotropy. MR‐PRESSO was used to test the presence of horizontal outliers. Leave‐one‐out analysis was utilized to ensure the reliability of the results. Results A higher genetic predisposition to any OA has a causal association with bladder cancer risk, while neither knee OA nor hip OA is causally linked to bladder cancer. MR‐Egger intercept analysis exhibited that any OA and knee OA had no pleiotropic effect on the risk of bladder cancer, and Cochran's Q test showed that any OA, knee OA and hip OA had no heterogeneity on bladder cancer risk. Neither MR PRESSO analysis nor leave‐one‐out analysis revealed any outlier SNPs. Conclusions This MR study exhibited a positive cause‐and‐effect relationship between any type of OA and bladder cancer risk, but not between site‐specific OA, knee OA and hip OA, and bladder cancer. Attention should be paid to the screening and prevention of bladder cancer in OA patients at any site.

Abstract Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.

Abstract Background Condyloma acuminatum (CA) is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective externally administered prescription used to treat CA; however, its molecular mechanism remains unclear. This study aimed to identify and experimentally validate the major active ingredients and prospective targets of FFGL. Methods Network pharmacology, transcriptomics, and enrichment analysis were used to identify the active ingredients and prospective targets of FFGL, which were confirmed through subsequent experimental validation using mass spectrometry, molecular docking, western blotting, and in vitro assays. Results The network pharmacology analysis revealed that FFGL contains a total of 78 active compounds, which led to the screening of 610 compound-related targets. Among them, 59 overlapped with CA targets and were considered to be targets with potential therapeutic effects. The protein–protein interaction network analysis revealed that protein kinase B (Akt) serine/threonine kinase 1 was a potential therapeutic target. To further confirm this result, we performed ribonucleic acid sequencing (RNA-seq) assays on HPV 18+ cells after FFGL exposure and conducted enrichment analyses on the differentially expressed genes that were screened. The enrichment analysis results indicated that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be a key pathway through which FFGL exerts its effects. Further in vitro experiments revealed that FFGL significantly inhibited the activity of HPV 18+ cells and reduced PI3K and Akt protein levels. A rescue experiment indicated that the reduction in cell viability induced by FFGL was partially restored after the administration of activators of the PI3K/Akt pathway. We further screened two active components of FFCL that may be efficacious in the treatment of CA: periplogenin and periplocymarin. The molecular docking experiments showed that these two compounds exhibited good binding activity to Akt1. Conclusion FFGL reduced HPV 18+ cell viability by inhibiting key proteins in the PI3K/Akt pathway; this pathway may represent an essential mechanism through which FFGL treats CA. Periplogenin and periplocymarin may play a significant role in this process.

In order to clarify the cause of formation of siderite cement, and study the influence of siderite cement on reservoir and its geological model, and explore the influence of siderite-bearing reservoir on oilfield development and production, the study of the cause of formation of siderite cement and its influence on physical properties was carried out. Based on conventional core analysis, thin section analysis and X-ray analysis, statistics on the types and characteristics of cements in middle-shallow reservoirs in the Enping oil area, Pearl River Mouth Basin, reveal that siderite cement is abundant. The redox state and sedimentary environment of the paleo-ocean were used to study the genetic mechanism of siderite and quantitatively study the influence of siderite on middle-shallow reservoir quality. The results show that siderite in the reservoir is the product of the combination of CO2 produced by the degradation of organic matter and Fe2+ enriched in pore water during diagenesis. It formed in the early diagenetic stage when the primary pores of sandstone developed, which has a positive significance for the preservation of the overall pores of the reservoir. However, the local cementation of siderite (mostly developed in thin argillaceous belts) is destructive to the reservoir because it occupies a large proportion of the primary pore space. The "permeability control" effect of siderite cement makes the vertical permeability of the muddy strip much lower than that in other directions, thus greatly increasing the shielding effect of the muddy thin layer on the bottom water, which is conducive to reservoir development. Due to the blocking of argillaceous belts, the reservoir geological pattern will change from bottom water reservoir to edge water reservoir and edge water reservoir to multilayer edge water reservoir, which can be exploited by corresponding development measures. The development of siderite leads to differences in the energy supply in the top, middle and edge of the reservoir, which can guide water injection and improve the well pattern strategy. The research results were applied in Oilfield B, where the horizontal strip interlayer of fulling siderite cements resulted in insufficient energy supply in the high position. By injecting hot water to increase energy, oil field production is doubled, and reservoir recovery is greatly improved.

Background: Low-temperature stress significantly restricts maize germination, seedling growth and development, and yield formation. However, traditional methods of evaluating maize seedling quality are inefficient. This study established a method of grading maize seedling quality based on phenotypic extraction and deep learning. Methods: A pot experiment was conducted using different low-temperature combinations and treatment durations at six different stages between the sowing and seedling phases. Changes in 27 seedling quality indices, including plant morphology and photosynthetic performance, were investigated 35 d after sowing and seedling quality grades were classified based on maize yield at maturity. The 27 quality indices were extracted, and a total of 3623 sample datasets were obtained and grouped into training and test sets in a 3:1 ratio. A convolutional neural network-based grading method was constructed using a deep learning model. Results: The model achieved an average precision of 98.575%, with a recall and F1-Score of 98.7% and 98.625%, respectively. Compared with the traditional partial least squares and back propagation neural network, the model improved recognition accuracy by 8.1% and 4.19%, respectively. Conclusions: This study provided an accurate grading of maize seedling quality as a reference basis for the standardized production management of maize in cold regions.

The deterioration of water quality caused by human activities has triggered significant impacts on aquatic ecosystems. Submerged macrophytes play an important role in freshwater ecosystem restoration. Understanding the relative contributions of the sources and environment to the adaptive strategies of submerged macrophytes is crucial for freshwater restoration and protection. In this study, the perennial submerged macrophyte Myriophyllum spicatum was chosen as the experimental material due to its high adaptability to a variable environment. Through conducting reciprocal transplant experiments in two different artificial environments (oligotrophic and eutrophic), combined with trait network and redundancy analysis, the characteristics of the plant functional traits were examined. Furthermore, the adaptive strategies of M. spicatum to the environment were analyzed. The results revealed that the plant source mainly influenced the operational pattern among the traits, and the phenotypic traits were significantly affected by environmental factors. The plants cultured in high-nutrient water exhibited a higher plant height, longer leaves, and more branches and leaves. However, their physiological functions were not significantly affected by the environment. Therefore, the adaptation strategy of M. spicatum to the environment mainly relies on its phenotypic plasticity to ensure the moderate acquisition of resources in the environment, thereby ensuring the stable and efficient operation of plant physiological traits. The results not only offered compelling evidence on the adaptation strategies of M. spicatum in variable environments but also provided theoretical support for the conservation of biodiversity and sustainable development.

Objective: This study aims to investigate the impact of Polyphyllin VII (PP7) on pulmonary hypertension (PH) and elucidate the underlying mechanism involving microRNA (miR)−205–5p/β-catenin. Methods: The PH rat model was induced through hypoxia exposure. The effects of intraperitoneal injection of PP7 on pulmonary artery tissue pathology, hemodynamics, miR-205–5p expression and β-catenin protein levels were assessed. In vitro, pulmonary arterial smooth muscle cells (PASMCs) were subjected to hypoxic conditions. Moreover, miR-205–5p and/or β-catenin were overexpressed through transfection. PASMCs were pre-cultured in 20 μM PP7, and subsequent measurements included proliferation, apoptosis and vascular remodeling protein expression. Results: PP7 ameliorated PH symptoms in rats, upregulated miR-205–5p expression and inhibited β-catenin protein expression. Furthermore, miR-205–5p upregulation inhibited β-catenin expression in PASMCs. The overexpression of β-catenin aggravated hypoxia-induced proliferation, inhibited apoptosis and further augmented VEGF and α-SMA protein expression. Additionally, miR-205–5p overexpression alleviated the hypoxia-induced PASMC proliferation and apoptosis by inhibiting β-catenin protein expression. Under hypoxic conditions, PP7 significantly elevated miR-205–5p while downregulating β-catenin protein expression. Furthermore, inhibiting miR-205–5p counteracted the inhibitory effect of PP7 on β-catenin, consequently blocking the regulatory role of PP7 in PASMC proliferation and apoptosis. Conclusion: PP7 likely modulates β-catenin protein levels by promoting miR-205–5p expression, thereby alleviating PH, vascular remodeling and airway smooth muscle remodeling.

BackgroundInfluenza outbreaks pose a significant threat to global public health. Traditional surveillance systems and simple algorithms often struggle to predict influenza outbreaks in an accurate and timely manner. Big data and modern technology have offered new modalities for disease surveillance and prediction. Influenza-like illness can serve as a valuable surveillance tool for emerging respiratory infectious diseases like influenza and COVID-19, especially when reported case data may not fully reflect the actual epidemic curve. ObjectiveThis study aimed to develop a predictive model for influenza outbreaks by combining Baidu search query data with traditional virological surveillance data. The goal was to improve early detection and preparedness for influenza outbreaks in both northern and southern China, providing evidence for supplementing modern intelligence epidemic surveillance methods. MethodsWe collected virological data from the National Influenza Surveillance Network and Baidu search query data from January 2011 to July 2018, totaling 3,691,865 and 1,563,361 respective samples. Relevant search terms related to influenza were identified and analyzed for their correlation with influenza-positive rates using Pearson correlation analysis. A distributed lag nonlinear model was used to assess the lag correlation of the search terms with influenza activity. Subsequently, a predictive model based on the gated recurrent unit and multiple attention mechanisms was developed to forecast the influenza-positive trend. ResultsThis study revealed a high correlation between specific Baidu search terms and influenza-positive rates in both northern and southern China, except for 1 term. The search terms were categorized into 4 groups: essential facts on influenza, influenza symptoms, influenza treatment and medicine, and influenza prevention, all of which showed correlation with the influenza-positive rate. The influenza prevention and influenza symptom groups had a lag correlation of 1.4-3.2 and 5.0-8.0 days, respectively. The Baidu search terms could help predict the influenza-positive rate 14-22 days in advance in southern China but interfered with influenza surveillance in northern China. ConclusionsComplementing traditional disease surveillance systems with information from web-based data sources can aid in detecting warning signs of influenza outbreaks earlier. However, supplementation of modern surveillance with search engine information should be approached cautiously. This approach provides valuable insights for digital epidemiology and has the potential for broader application in respiratory infectious disease surveillance. Further research should explore the optimization and customization of search terms for different regions and languages to improve the accuracy of influenza prediction models.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have been demonstrated to act as key regulators in various pathophysiological processes and play significant roles in a wide range of human diseases, particularly cancer. Current research highlights the aberrant expression of microRNA-488 (miR-488) in multiple human diseases and its critical involvement in disease initiation and progression. Moreover, the expression level of miR-488 has been linked to clinicopathological features and patient prognosis across different diseases. However, a comprehensive systematic review of miR-488 is lacking. Therefore, our study aims to consolidate the current knowledge surrounding miR-488, with a primary focus on its emerging biological functions, regulatory mechanisms, and potential clinical applications in human diseases. Through this review, we aim to establish a comprehensive understanding of the diverse roles of miR-488 in the development of various diseases.

Collapse columns which can usually destroy the integrity of strata are widespread in the Carboniferous and Permian coalfields for North China type. The incubation and development process of collapse column could change the mechanical property and acoustic feature of surrounding rock. Rock wave velocity was tested under uniaxial loading and the relationship of wave velocity and stress was obtained before plastic deformation. Based on the physical property parameters of rock and coal, homogeneous medium for three symmetrical layers was established. For the full-wave-fields forward modeling, elastic wave equations were analyzed through finite difference method. Wave field snapshot, plane-wave seismogram and frequency dispersion curve were obtained after analysis for the collapse column in the model. In-seam seismic wave field was inversed through velocity analysis and CT analysis of energy attenuation coefficient. The effect on inversion result was researched for different physical property parameters of collapse column and observing system parameters. The research results showed that seismic wave field was decayed with the increase of propagation distance. In-seam seismic wave signal was weakened or even disappeared when the collapse column is encountered. When the wave velocity of the collapse column is larger than that of the surrounding rock or smaller than that of the coal seam, an obvious diffraction in-seam wave is formed and the Airy phase pulsates. When the wave velocity of the collapse column is less than that of the coal seam, it is characterized by low speed anomaly, and the collapse column with low speed or high speed produces obvious energy attenuation anomaly. When the field observation system is arranged, the gun spacing and channel spacing can be selected as 20 m.

Abstract Background The impact of coronavirus diseases 2019 (COVID-19) related non-pharmaceutical interventions (NPIs) on influenza activity in the presence of other known seasonal driving factors is unclear, especially at the municipal scale. This study aimed to assess the impact of NPIs on outpatient influenza-like illness (ILI) consultations in Beijing and the Hong Kong Special Administrative Region (SAR) of China. Methods We descriptively analyzed the temporal characteristics of the weekly ILI counts, nine NPI indicators, mean temperature, relative humidity, and absolute humidity from 2011 to 2021. Generalized additive models (GAM) using data in 2011–2019 were established to predict the weekly ILI counts under a counterfactual scenario of no COVID-19 interventions in Beijing and the Hong Kong SAR in 2020–2021, respectively. GAM models were further built to evaluate the potential impact of each individual or combined NPIs on weekly ILI counts in the presence of other seasonal driving factors in the above settings in 2020–2021. Results The weekly ILI counts in Beijing and the Hong Kong SAR fluctuated across years and months in 2011–2019, with an obvious winter-spring seasonality in Beijing. During the 2020–2021 season, the observed weekly ILI counts in both Beijing and the Hong Kong SAR were much lower than those of the past 9 flu seasons, with a 47.5% [95% confidence interval (CI): 42.3%, 52.2%) and 60.0% (95% CI: 58.6%, 61.1%) reduction, respectively. The observed numbers for these two cities also accounted for only 40.2% (95% CI: 35.4%, 45.3%) and 58.0% (95% CI: 54.1%, 61.5%) of the GAM model estimates in the absence of COVID-19 NPIs, respectively. Our study revealed that, “Cancelling public events” and “Restrictions on internal travel” measures played an important role in the reduction of ILI in Beijing, while the “restrictions on international travel” was statistically most associated with ILI reductions in the Hong Kong SAR. Conclusions Our study suggests that COVID-19 NPIs had been reducing outpatient ILI consultations in the presence of other seasonal driving factors in Beijing and the Hong Kong SAR from 2020 to 2021. In cities with varying local circumstances, some NPIs with appropriate stringency may be tailored to reduce the burden of ILI caused by severe influenza strains or other respiratory infections in future. Graphical Abstract

Abstract Background Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential. Results CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change. Conclusions Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.

Abstract Background Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. Methods HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. Results In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P

ABSTRACT: Infections with Scedosporium and Lomentospora species are usually found in patients who are immunodeficient, particularly in the transplant population. However, they are relatively rare in patients who are immunocompetent, which is especially useful in ruling out near-drowning and aspiration situations. Here, we report a case of a patient who is immunocompetent, with clinically suspected community-acquired pneumonia caused by Lomentospora prolificans detected by metagenomics next-generation sequencing (mNGS) and polymerase chain reaction from bronchoalveolar lavage fluid. This case highlights mNGS in the clinical diagnosis of pulmonary invasive fungal disease. mNGS is proposed as an important adjunctive diagnostic approach for rare pathogens.

Abstract Background Dandelion is an herb with high nutritional and medicinal values, which has been listed in Chinese Pharmacopeia, European Pharmacopoeia and British Pharmacopoeia, gaining increasing acceptance around the world. However, the current quality control of dandelion is lagging behind. Only in Chinese Pharmacopeia, cichoric acid is used as a marker compound for its quality evaluation, whereas, it can not comprehensively reflect the bioactivity of dandelion. Methods This study developed a strategy by integrating chemometrics with in silico pharmacology to reveal the bioactive markers of dandelion for its quality control. Firstly, the major chemicals in dandelion were characterized using HPLC-DAD-MS/MS, and the corresponding antioxidant and anti-inflammatory activities were evaluated in vitro. Subsequently, the active components were screened by relating the chemicals and bioactivity of dandelion via grey relational assay and partial least squares regression analysis. The potential active components were then subjected to a validation for their activities. Moreover, in silico pharmacology was utilized to evaluate the contribution of active components to efficacy. Results A total of 22 phenolic compounds were characterized. Among them, cichoric acid, caffeic acid and luteolin were identified as quality markers owing to their good correlations with the bioactivities of dandelion. These three markers were quantified in frequently-used dandelion species, viz. Taraxacum mongolicum Hand.-Mazz. (TAM) and T. officinale F. H. Wigg. (TAO). TAM, with acceptably higher content of cichoric acid and caffeic acid, showed better antioxidant activity than TAO. While TAO included higher content of luteolin, presenting slightly more effective in anti-inflammation. Conclusion An useful strategy for the quality marker discovery was successfully designed. And the results provided more knowledge for the quality evaluation of dandelion.