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Abstract Background Patients with choriocarcinoma (CC) accompanying chemoresistance conventionally present a poor prognosis. Whether ras protein activator like-1 (RASAL1) functions as a tumor promoter or suppressor depends on tumor types. However, the role of RASAL1 in process of chemoresistance of CC and underlying molecular mechanism remain elusive. Methods The expression pattern of RASAL1 in CC cells and tissues was measured using Western blotting, immunohistochemistry and qRT-PCR. Cell viability and proliferative ability were assessed by MTT assay, Tunnel assay and flow cytometric analysis. Additionally, the stemness was evaluated by the colony formation and tumor sphere formation. Methotrexate (MTX) was applied to exam the chemosensitivity of CC cells. Results The expression of RASAL1 was reduced both at the protein and mRNA levels in CC tissues and cells compared to hydatidiform mole (HM) and invasive mole (IM). Loss of RASAL1 was attributed to its promoter hypermethylation and could be restored by 5-Aza. Knock-down of RASAL1 promoted the viability, proliferative potential, stemness and EMT phenotype of JEG-3 cells. However, induced overexpression of RASAL1 by 5-Aza significantly prohibited cell proliferation and stemness potential of the JAR cell. Additionally, the xenograft model indicated that knockdown of RASAL1 led to a remarkable increase of tumor volume and weight in comparison with its counterpart. Moreover, the stimulatory activity brought by decrease of RASAL1 could be deprived by β-catenin inhibitor XAV 939, yet the suppressive activity resulted from its promoter demethylation could be rescued by β-catenin activator BML-284, indicating that function of RASAL1 depends on β-catenin. Besides, the co-immunoprecipitation assay confirmed the physical binding between RASAL1 and β-catenin. Further investigations showed hypermethylated RASAL1 was regulated by TET2 but not DNMTs. Conclusion Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating β-catenin both in vitro and in vivo.

Abstract Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z 2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

The development and utilization of environment-friendly energy is imminent with global energy shortage and climate change becoming increasingly serious. The advancement and utilization of environment-friendly energy, including photocatalytic hydrogen production, electrocatalytic pollutant removal, and the development of electrochemical energy storage devices, have emerged as prominent research topics. A variety of modern analysis techniques provide strong support in these related studies, such as X-ray absorption spectroscopy (XAS) for investigating the active site geometry and electronic structure of photocatalysts, synchrotron radiation X-ray photoelectron spectroscopy (SR-XPS) for real-time monitoring of interatomic electron excitation and transfer in photocatalysts, in situ electron paramagnetic resonance spectroscopy (EPR) for the detection of free radicals in photocatalysis reactions, Raman spectroscopy (RS) for analyzing the interfacial structure of electrochemical reactions, and in situ transmission electron microscopy (TEM) for studying catalyst structure and reactivity in photocatalytic reactions. While these techniques provide abundant information for the mechanistic aspects of the associated chemical processes, it remains challenging to conduct further identification and structural analysis of the reaction intermediates at a molecular level. Due to the ability in rapid identification of the components in complex system, mass spectrometry (MS) has been widely used in the new energy fields such as photocatalytic reaction, electrocatalytic reaction, and the development of electrochemical energy storage devices. This review introduced the application of mass spectrometry techniques, including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), differential electrochemical mass spectrometry (DEMS), and electrospray ionization mass spectrometry (ESI-MS), in the detection of transient intermediates and products as well as the exploration of reaction mechanisms. Modern mass spectrometry offers critical support for the mechanism analysis of photocatalytic reactions aimed at the mineralization of organic pollutants, hydrogen generation, CO2 reduction, N2 fixation, and organic synthesis. It also provides distinct advantages for real-time product monitoring, isotopic labeling analysis, and the capture and identification of short-lived intermediates in electrocatalytic processes, such as hydrogen evolution, oxygen evolution, CO2 reduction, N2 reduction, and organic synthesis. By analyzing reaction products and intermediates in electrochemical energy storage devices through mass spectrometry, it is possible to elucidate the nature of energy storage and conduct rational design of high-performance materials. Modern mass spectrometry facilitates both offline detection of products and online identification of reaction intermediates, enhancing the understanding of reaction kinetics and elucidating mechanisms when combined with theoretical calculations. Thus, modern mass spectrometry has become a powerful tool for the study of reaction mechanisms. The challenges and prospects of mass spectrometry in the fields of photocatalytic degradation, photocatalytic synthesis, electrocatalytic reduction, electrocatalytic synthesis, lithium-ion batteries, and lithium-sulfur batteries were also discussed in this review. While current mass spectrometry techniques can detect transient intermediates, challenges persist in identifying the reaction intermediates with lower concentrations and reduced stability. Therefore, optimizing the sampling systems and mass analyzers is crucial to improve the sampling speed, transfer efficiency, and analysis throughput. Understanding complex reaction mechanisms requires correlating reaction intermediates with various conditions, such as reaction time, radiation wavelength, and potential. This necessitates a spatial integration between the reactor and the mass spectrometer to preserve the true form of intermediates and ensure accurate signal transmission that reflects the pertinent reaction parameters. Integrating mass spectrometry to analyze the morphology and structure of reaction intermediates and products with theoretical calculations may enable the construction of a comprehensive, multi-dimensional reaction theory system. Ultimately, employing this theoretical framework to advance experimental research could represent a novel idea in the research filed.

In order to solve the problems of low efficiency and cumbersome process of Pichia pastoris genetic manipulation, secretory genetic manipulation tools were constructed and optimized to improve their industrial production and application value. Firstly, the α-amylase was employed as the reporter protein, and the non-integrated expression plasmid was constructed by fusing the self-replicating sequence. Secondly, endogenous signal peptides that best match the target protein were quickly screened and evaluated using universal primers and POE-PCR. Finally, a nutrition-dependent screening marker was constructed with phosphite as the sole phosphorus source. The results indicate that non-integrated plasmids express α-amylase with 2-fold and 1.6-fold higher enzyme activity compared to integrated plasmids, respectively; The use of FLO10, EXG1, and MSB2 signal peptides results in 2.5-fold, 1.94-fold, and 1.75-fold higher α-amylase activity than the conventional signal peptide α-MF, respectively; Arecombinant strain for heterologous expression of α-amylase is successfully screened using the phosphite dehydrogenase gene (ptxD). The process of gene operation is simplified, the genetic operation tools are improved, and green, safe, and low-cost nutrition-dependent screening markers are provided, which lays a foundation for the application and promotion of the Pichia pastoris secretory expression system.

Abstract mRNA vaccines against SARS-CoV-2 have revolutionized vaccine development, but their immunological mechanisms are not fully understood. Here, we investigate injection site responses of mRNA vaccines by generating a comprehensive single-cell transcriptome profile upon lipid nanoparticle (LNP) or LNP-mRNA challenge in female BALB/c mice. We show that LNP-induced stromal pro-inflammatory responses and mRNA-elicited type I interferon responses dominate the initial injection site responses. By tracking the fate of delivered mRNA, we discover that injection site fibroblasts are highly enriched with the delivered mRNA and that they express IFN-β specifically in response to the mRNA component, not to the LNP component of mRNA vaccines. Moreover, the mRNA-LNP, but not LNP alone, induces migratory dendritic cells highly expressing IFN-stimulated genes (mDC_ISGs) at the injection site and draining lymph nodes. When co-injected with LNP-subunit vaccine, IFN-β induces mDC_ISGs at the injection site, and importantly, it substantially enhances antigen-specific cellular immune responses. Furthermore, blocking IFN-β signaling at the injection site significantly decreases mRNA vaccine-induced cellular immune responses. Collectively, these data highlight the importance of injection site fibroblasts and IFN-β signaling during early immune responses against the mRNA vaccine and provide detailed information on the initial chain of immune reactions elicited by mRNA vaccine injection.

Abstract Background The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments. Methods The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized. Results Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2. Conclusions Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

Abstract Background Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15–39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). Result In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. Conclusion ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.

Abstract The triglyceride-glucose (TyG) index is a novel marker of insulin resistance that has been strongly associated with many diseases related to metabolic disorders, such as diabetes, coronary heart disease, myocardial infarction, obesity, nonalcoholic fatty liver disease, and stroke. However, whether the TyG index is associated with the prevalence of gallstones has not been determined. Therefore, the purpose of this study was to evaluate the relationship between the TyG index and the prevalence of gallstones in American adults, as well as the age at which adults in America undergo their first gallstone surgery. We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to March 2020. Based on the goal of our study, comprehensive inclusion and exclusion criteria were created. A logistic regression analysis, dose–response curve, and subgroup analysis were computed to assess the relationship between the TyG index and gallstone prevalence and age at first surgery for gallstone. A total of 3905 participants aged > 20 years were included in our study, of whom 421 had a self-reported history of gallstones. A total of 1884 (48.2%) males and 2021 (51.8%) females were included. After confounders adjustment, it was found single-unit increases in the TyG index were linked with a 25.0% increase in gallstone prevalence (odds ratio [OR] = 1.25, 95% confidence interval [95%CI]: 1.04, 1.51). After conversion of the TyG index values from continuous to categorical variables with tertiles, a marked 48% increase in gallstone incidence was found in tertile 3 relative to tertile 1 (OR = 1.48, 95% CI: 1.09, 1.99). The dose–response curve results indicated positive associations between gallstone prevalence and the TyG index, while the latter was negatively associated with age at first gallstone surgery. Based on subgroup analysis, the positive association between TyG index and high-incidence of gallstones was more significant in females (OR = 1.39, 95% CI: 1.09, 1.77), age

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. However, the relationship between core stability and the effectiveness of athletic performance, particularly in executing the wing kick, remains ambiguous, impeding coaches and athletes in their efforts to improve athletic performance. A total of 26 male participants (height: 167.21 ± 7.29 cm; weight: 62.07 ± 8.03 kg; age: 24.69 ± 2.53 years) participated, and they have been practicing Taekwondo for more than 10 years. Kinematic and kinetic data were collected using 13 infrared cameras at 120 Hz, muscle activity data were collected using epidermal electromyography, and participants’ core stability level were measured using the Sahrmann Core Stability Test (SCST) for correlation with other variables. Core stability levels showed a strong negative correlation with execution time (r = −0.7144, p < 0.001) of the aerial phase of the wing kick as did angular momentum in most lower limb segments (thigh X axis, r = −0.6435, p < 0.001, shank X axis, r = −0.62008, p < 0.001, foot X axis, r = −0.7033, p < 0.001). Bilateral rectus abdominis (RA) showed strong correlations with muscle activation (left rectus abdominis (LRA) of left foot take off-left knee max extension (LTO-LKMF) phase, r = 0.5351, p < 0.001, right rectus abdominis (RRA) of LTO-LKMF phase, r = −0.5628, p < 0.001), and high levels of core stability were associated with better core-muscle coupling. We conclude that incorporating core stability training into taekwondo training has the potential to improve wing kick performance.

The conventional petroleum field in Jiyang Depression has always been the main battlefield of exploration and development in Shengli Oilfield. It has experienced more than 60 years of exploration and development and entered the mature exploration stage as a whole， but it still has a relatively large scale of reserve increase every year， which is not consistent with the traditional growth trend of proven petroleum-in-place in oil and gas-bearing basins. The critical issues concerning the exploration decisions of Shengli Oilfield need to be clarified urgently， including the growth law of the conventional proven petroleum-in-place in Jiyang Depression， the strong trend of reserve increase， and the main fields for reserve increase. By analyzing the exploration process of Jiyang Depression， the geological characteristics， resource conditions， exploration investment， theory and technology， resource sequence， and other exploration elements were analyzed， revealing the exploration discovery law of conventional petroleum in Jiyang Depression. The broom-shaped model prediction method and proven rate method of resource were used to predict the growth trend of conventional proven petroleum-in-place. The scale and favorable direction of future reserve increase of conventional petroleum in Jiyang Depression were clarified by analyzing the main fields with reserve increase. The results show that the complex geological characteristics of Jiyang Depression and the relatively abundant remaining resources determine the diversity of exploration objects， the tortuosity of the exploration process， and the long-term nature of exploration history. The conventional petroleum in Jiyang Depression can still maintain a long period of stable reserve increase under conditions of ensuring a relatively stable exploration investment， continuing to innovate the exploration theory and key technologies， and maintaining a relatively reasonable resource sequence. Jiyang Depression can still produce about 2.5 × 108 t of conventional proven petroleum-in-place in the next 10 years under the current economic and technical conditions and the relative guarantee of exploration investment. It is pointed out that the Neogene river sandstone reservoir， lithologic oil and gas reservoirs in the Upper Submember of the 4th Member of the Eocene Shahejie Formation（Es4U）-the Lower 3rd Member of the Eocene Shahejie Formation（Es3L）， and other mature fields are still the ballast stones for stable reserve increase. Kongdian Formation-the deep field of the Lower Submember of the 4th Member of the Eocene Shahejie Formation（Es4L） is an essential field for large-scale reserve increase， and the pre-Paleogene buried hill is a favorable direction for the petroleum enrichment and high yield. In the future， the exploration progress in the unconventional and new energy fields should be closely tracked， and the research results of the growth law and the reserve increase trend of conventional proven petroleum-in-place in Jiyang Depression should be constantly improved and revised to make them more conform to the development trend of oilfield exploration and guide the oilfield exploration decisions.

Abstract Background Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. Methods This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. Results During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27). Conclusions Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Based on the data of outcrop, core, logging, gas testing, and experiments, the natural gas accumulation and aluminous rock mineralization integrated research was adopted to analyze the controlling factors of aluminous rock series effective reservoirs in the Ordos Basin, NW China, as well as the configuration of coal-measure source rocks and aluminous rock series reservoirs. A natural gas accumulation model was constructed to evaluate the gas exploration potential of aluminous rock series under coal seam in the basin. The effective reservoirs of aluminous rock series in the Ordos Basin are composed of honeycomb-shaped bauxites with porous residual pisolitic and detrital structures, with the diasporite content of greater than 80% and dissolved pores as the main storage space. The bauxite reservoirs are formed under a model that planation controls the material supply, karst paleogeomorphology controls diagenesis, and land surface leaching improves reservoir quality. The hot humid climate and sea level changes in the Late Carboniferous–Early Permian dominated the development of a typical coal-aluminum-iron three-stage stratigraphic structure. The natural gas generated by the extensive hydrocarbon generation of coal-measure source rocks was accumulated in aluminous rock series under the coal seam, indicating a model of hydrocarbon accumulation under the source. During the Upper Carboniferous–Lower Permian, the relatively low-lying area on the edge of an ancient land or island in the North China landmass was developed. The gas reservoirs of aluminous rock series, which are clustered at multiple points in lenticular shape, are important new natural gas exploration fields with great potential in the Upper Paleozoic of North China Craton.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (DosR), White B-like (Wbl) family, Toxin-Antitoxin (TA) systems, sigma factors, and MprAB. We outline the progress in vaccine and drug development associated with Mtb dormancy.

Abstract Background Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain. Methods This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve. Results During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P

Abstract Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2−) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2− breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2− breast cancer patients.

Buildings account for more than one third of global energy consumption and carbon emissions, making the optimization of their energy use crucial for sustainability. Advanced Metering Infrastructures data offers a rich source of information for understanding and improving building energy performance, yet existing frameworks for leveraging this data are limited. This paper presents a comprehensive data-mining framework for analyzing Advanced Metering Infrastructures data at multiple temporal and spatial scales, beneficial for building owners, operators, and utility companies. Utilizing hourly electricity consumption data for the east region of Portland, Oregon, the study systematically extracts key statistics such as start hour, duration, and peak hour of load periods across daily, weekly, and annual evaluation windows. The framework employs a list of techniques including load-level detection, home vacancy detection, and weather-sensitivity analysis and statistical methods to provide detailed insights into building energy dynamics. As an unsupervised study, it reveals patterns and trends without predefined labels or categories. Key findings highlight the substantial impact of the COVID-19 pandemic on residential energy use, uncover patterns like intraday load variations, weekly consumption trends, and annual weather sensitivity. The insights gained can potentially inform better energy management strategies, support grid operations and planning, guide policy-making for energy efficiency improvements, as well as improve input and assumptions in the building energy modeling. This study opens pathways for future research, including integrating more data sources and collaborating with utility companies to validate hypotheses and further explore building energy use insights.

Background: Hypertension is often accompanied by anxiety and sleep disorders, which further complicate the disease. This study aimed to evaluate the feasibility and effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in patients with hypertension and anxiety or sleep disorders. Methods: Eligible participants were randomly assigned to the 10 Hz TEAS, 2 Hz TEAS, or routine treatment groups in a 1:1:1 ratio. Participants continued their routine treatment during the trial, while those in the two TEAS groups received 12 sessions of 30-min TEAS treatment with different stimulation frequencies. The feasibility parameters were successful screening probability, enrollment rate, and dropout rate. The primary outcome was the change in office systolic blood pressure from baseline to week four. Secondary outcomes included changes in office diastolic blood pressure, heart rate, Pittsburgh Sleep Quality Index score, and Generalized Anxiety Disorder 7-item scale score from baseline to week four. Results: Eighty-eight participants (age 58.0 [51.0, 63.0] years; 49 women) were randomized. The successful screening probability was 56.1 %, the enrollment rate was 3.1 participants per week, and the dropout rate was 14.8 %. The change in office systolic blood pressure from baseline to week four was −2.8 ± 13.6 mm Hg, −6.4 ± 10.0 mm Hg, and −7.2 ± 11.2 mm Hg, respectively, in the 10 Hz TEAS, 2 Hz TEAS, and routine treatment groups (P = 0.332). No significant differences were noted, except for a change in the Pittsburgh Sleep Quality Index score (P = 0.014). Both 10 Hz (P = 0.024) and 2 Hz TEAS (P = 0.039) significantly improved sleep quality compared to routine treatment. Conclusions: In patients with hypertension having anxiety or sleep disorders, this study did not demonstrate the superiority of TEAS over routine treatment but did show an improvement in sleep quality and a downward trend in diastolic blood pressure. Therefore, a largescale trial is warranted.

The aim of this study was to investigate the effects of dietary supplementation with selenium yeast (YS) and zinc lysine (ZL) on goose semen quality, testicular tissue structure, reproductive hormone levels, antioxidant capacity and egg fertilization rate. A total of 24 male and 72 female geese, all 180-days-old, were selected and divided into four treatment groups, each with a consistent body weight. Each treatment group had six male and 18 female geese (1:3 ratio of male to female). The control (Ⅰ) group was fed a basal diet. The YS (Ⅱ) group was fed a basal diet supplemented with 0.3 mg/kg of selenium-yeast. The ZL (Ⅲ) group was fed a basal diet supplemented with 106.05 mg/kg of zinc-lysine. The YS + ZL (Ⅳ) group was fed a basal diet supplemented with 0.3 mg/kg of selenium-yeast and 106.05 mg/kg of zinc-lysine. The experimental period lasted for 91 days. The results showed that supplementation of 0.3 mg/kg YS and 106.05 mg/kg ZL significantly increased sperm motility (P < 0.05), and significantly increased VAP, VSL, VCL, ALH, LIN, MAD and STR (P < 0.01) compared with the control group. Compared with the control group, dietary supplementation of YS and ZL increased the number of germ cells and Johnson score in groups Ⅱ, Ⅲ and Ⅳ (P < 0.01), and the number of spermatogonia and sertoli cells were significantly different from the control group (P < 0.05). Dietary supplementation of YS and ZL could increase the reproductive hormone level (P < 0.05) and serum antioxidant capacity (P < 0.05), and the fertilization rate showed a certain promoting trend (P = 0.09). In conclusion, dietary supplementation of 0.3 mg/kg YS and 106.05 mg/kg ZL can improve semen quality, promote testicular development, maintain stability of the fertilization rate, and increase reproductive hormone levels and the serum antioxidant capacity of geese.

Introduction and Objectives: We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC). Materials and Methods: From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups. Results: Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055). Conclusions: Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.