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The aim of this study is to analyze how undergraduate learners seek academic help online at a public university in the United States with Q methodology. Upon completion of the study, we identified three groups of help-seekers. The first group, informal and personal help-seekers, sought help from close friends or classmates to solve problems. The second group, formal and impersonal help-seekers, relied on instructors as their primary source of help, followed by instructional materials such as course websites, syllabi, and rubrics. The participants in the third group expressed a significant reluctance to seek help from instructors and preferred alternative options like tutoring centers, search engines, and discussion boards. Contradicting opinions about help-seeking sources existed, with reasons explored. Implications and recommendations for future studies were also discussed.

Abstract Previous research on the association between Family Doctor Contract Services (FDCS) and health has only considered a single indicator of health and has not considered the endogeneity of independent variables. This study aimed to evaluate the association from a multidimensional perspective of the health of middle-aged and older people using the instrumental variables method and determine the underlying mechanisms. Using data from the 2018 China Health and Retirement Longitudinal Study surveys, a total of 19,438 sample was obtained. Health was measured by health related-quality of life (HR-QoL), subjective well-being, and cognitive function. The instrumental variables method was used to estimate the association. Mediation analysis was employed to analyze the underlying mechanisms. The results of the instrumental variables method showed a correlation between FDCS and health, such as HR-QoL (η = 33.714, p

Abstract Accelerating the design of Ni-based single crystal (SX) superalloys with superior creep resistance at ultrahigh temperatures is a desirable goal but extremely challenging task. In the present work, a deep transfer learning neural network with physical constraints for creep rupture life prediction at ultrahigh temperatures is constructed. Transfer learning enables deep learning model breaks through the generalization performance barrier in the extrapolation space of ultrahigh temperature creep properties in the case of a very small dataset, which is the key to achieving the above design goal. Transfer learning is demonstrated to be effective in utilizing the prior compositional sensitivities information contained in the pre-trained model, and motivates the fine-tuned model to capture the particular relationship between composition and creep rupture life at ultrahigh temperature. Aiming to find advanced SX superalloys applied at 1200 °C, the proposed transfer learning-based model guides us to design a superalloy with a verified creep rupture life of ~170 h at 80 MPa, which exceeds the state-of-art value by 30%. The improved γ/γ′ interface strengthening, which is effectively regulated by the Mo/Ta ratio to form γ′ rafting with longer, flatter interfaces and achieve stronger interfacial bonding, is revealed as the dominant mechanism behind combining experiments and first-principles calculations. Moreover, the excellent extrapolation ability of the proposed model is further confirmed to enhance the efficiency of active learning by reducing its dependence on the initial dataset size. This study provides a pioneering AI-driven approach for the rapid development of Ni-based SX superalloys applied in advanced aero-engine blades.

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

Abstract Because of their large surface areas, nanotubes and nanowires demonstrate exquisite mechanical coupling to their surroundings, promising advanced sensors and nanomechanical devices. However, this environmental sensitivity has resulted in several ambiguous observations of vibrational coupling across various experiments. Herein, we demonstrate a temperature-dependent Radial Breathing Mode (RBM) frequency in free-standing, electron-diffraction-assigned Double-Walled Carbon Nanotubes (DWNTs) that shows an unexpected and thermally reversible frequency downshift of 10 to 15%, for systems isolated in vacuum. An analysis based on a harmonic oscillator model assigns the distinctive frequency cusp, produced over 93 scans of 3 distinct DWNTs, along with the hyperbolic trajectory, to a reversible increase in damping from graphitic ribbons on the exterior surface. Strain-dependent coupling from self-tensioned, suspended DWNTs maintains the ratio of spring-to-damping frequencies, producing a stable saturation of RBM in the low-tension limit. In contrast, when the interior of DWNTs is subjected to a water-filling process, the RBM thermal trajectory is altered to that of a Langmuir isobar and elliptical trajectories, allowing measurement of the enthalpy of confined fluid phase change. These mechanisms and quantitative theory provide new insights into the environmental coupling of nanomechanical systems and the implications for devices and nanofluidic conduits.

In order to sort out the research process and hotspots of honey safety, this paper was based on the China national knowledge infrastructure (CNKI) database and the Web of Science (WOS) core collection, utilizing CiteSpace software to analyze and visualize publication trends, journals, authors, institutions, countries (regions), keywords, and other relevant information. The aforementioned databases yielded a total of 169 Chinese and 281 English literatures. The analysis revealed that the number of publications in Chinese literature on honey safety had been steadily increasing since 2011. The number of publications in English literature had displayed an oscillating upward trend since 2007, with a higher volume of publications in English literature over the past fifteen years compared to Chinese literature. ZHANG Q and GUNDUZ A were the most prolific authors in Chinese and English literature, respectively. While there were established cooperative relationships between researchers in both fields, collaborations between different groups remained relatively limited. Journal of Bee and Food Chemistry were the leading journals for publications on honey safety in English and Chinese, respectively. Both English and Chinese publishing journals primarily focused on the food industry. Yunnan Province Center for Disease Control and Prevention and Karadeniz Technical University were the research institutions with the highest publication output in Chinese and English, respectively. However, there was limited collaboration between research institutes in China. Turkey was the most influential country among the study countries (regions), followed by China, Poland, and New Zealand. During the initial stages of research, Chinese literature primarily explored topics such as "botulinum toxin" "pollen plants" "Triperygium wilfordii Hook. f." and "honey poisoning". However, after 2000, advancements in technologies such as chromatography, spectroscopy, and scanning electron microscopy led to the emergence of new keywords like "melissopalynology" and "gas chromatography". Consequently, gas chromatography, liquid chromatography, liquid-mass spectrometry, and scanning electron microscopy gained popularity as methods for detecting honey safety in research. During the early stages of research, English literature primarily delved into topics such as "pyrrolizidine alkaloids" "mad honey" "grayanotoxin" and "natural toxicants". This indicates that during this time, the primary emphasis was on studying toxic honey and natural toxins found in honey, specifically pyrrolizidine alkaloids and grayanotoxin. As technologies such as chromatography advanced, keywords like "mass spectrometry" began to emerge. It could be seen that the research in Chinese and English literature was focused on similar topics, such as toxic honey, honey poisoning, and the detection and tracing of toxic components in honey. However, there were slight differences in emphasis. In China, the main toxic nectar plants were Triperygium wilfordii Hook. f., Gelsemium elegans (Gardn. & Champ.) Benth. and Macleaya cordata (Willd.) R. Br., while the main toxic components detected in honey were triptolide and koumine. In foreign countries, honey poisoning incidents were mostly caused by grayanotoxin, pyrrolizidine alkaloids or tutin. This study provides reference for analyzing the research content and development process of honey safety and identifying research hotspots.

To explore the structural dynamic characteristics of the impeller and shaft system of the axial flow pump as turbine, the variation law of impeller transient equivalent stress, deformation, and the impeller and shaft system mode are analyzed by the transient fluid-structure interaction method. Findings indicate that the equivalent stress is centralized at the blade root around the hub and tends to decrease as it moves towards the shroud. The maximum equivalent stress at 1.0Qbep and 1.1Qbep is 1.26 times and 2.0 times higher than that at 0.8Qbep. Blade deformation is significantly influenced by flow rate. The maximum deformation of the blade at 1.0Qbep and 1.1Qbep is 1.6 times and 3.6 times higher than that at 0.8Qbep. The impeller and shaft system with prestress in dry mode has an average natural frequency of the first 10 orders that is 16.7 Hz higher than without prestress. However, with the fluid adding mass and flow damping, the average natural frequency of the first 10 orders of the impeller and shaft system in wet mode is reduced by 278.08 Hz compared with dry mode. In fact, the impeller and shaft system of the axial flow pump as turbine is not prone to vibration.

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.

Abstract Disulfidptosis is a recently identified mode of regulated cell death. Regulating disulfidptosis in carcinoma is a promising therapeutic approach. Long non-coding RNAs (lncRNAs) have been reported to be related to the occurrence and development of many cancers. Disulfidptosis-related lncRNAs (DRLs) in HPV-negative oral squamous cell carcinoma (OSCC) have not been studied. Based on The Cancer Genome Atlas (TCGA) database, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to identify overall survival related DRLs and construct the signature. Kaplan–Meier, time-dependent receiver operating characteristics (ROC) and principal component analyses (PCA) were explored to demonstrate the prediction potential of the signature. Subgroup analysis stratified by different clinicopathological characteristics were conducted. Nomogram was established by DRLs signature and independent clinicopathological characteristics. The calibration plots were performed to reveal the accuracy of nomogram. Immune cell subset infiltration, immunotherapy response, drug sensitivity analysis, and tumor mutation burden (TMB) were conducted. Underlying functions and pathways were explored by Gene Set Enrichment Analysis (GSEA) analysis. Previous lncRNA signatures of OSCC were retrieved from PubMed for further validation. Gene expression omnibus (GEO) datasets (GSE41613 and GSE85446) were merged as an external validation for DRLs signature. Consensus clustering analysis of DRLs signature and experimental validation of DRLs were also explored. This research sheds light on the robust performance of DRLs signature in survival prediction, immune cell infiltration, immune escape, and immunotherapy of HPV-negative OSCC.

Abstract Synthetic hexaploid wheats (SHWs) are effective genetic resources for transferring agronomically important genes from wild relatives to common wheat (Triticum aestivum L.). Dozens of reference-quality pseudomolecule assemblies of hexaploid wheat have been generated, but none is reported for SHW-derived cultivars. Here, we generated a chromosome-scale assembly for the SHW-derived cultivar ‘Chuanmai 104’ based on PacBio HiFi reads and chromosome conformation capture sequencing. The total assembly size was 14.81 Gb with a contig N50 length of 58.25 Mb. A BUSCO analysis yielded a completeness score of 99.30%. In total, repetitive elements comprised 81.36% of the genome and 122,554 high-confidence protein-coding gene models were predicted. In summary, the first chromosome-level assembly for a SHW-derived cultivar presents a promising outlook for the study and utilization of SHWs in wheat improvement, which is essential to meet the global food demand.

Abstract Oral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor (A2AR) on trigeminal ganglia. Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.

Abstract Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Abstract. Background:. Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China. Methods:. Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45–64 years and males aged 35–64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg. Results:. A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs. 4.82% [13,868/287,899], χ2 = 187.52, P

Based on the latest results of near-source exploration in the Middle and Lower Jurassic of the Tuha Basin, a new understanding of the source rocks, reservoir conditions, and source-reservoir-cap rock combinations of the Jurassic Shuixigou Group in the Taibei Sag is established using the concept of the whole petroleum system, and the coal-measure whole petroleum system is analyzed thoroughly. The results are obtained in three aspects. First, the coal-measure source rocks of the Badaowan Formation and Xishanyao Formation and the argillaceous source rocks of the Sangonghe Formation in the Shuixigou Group exhibit the characteristics of long-term hydrocarbon generation, multiple hydrocarbon generation peaks, and simultaneous oil and gas generation, providing sufficient oil and gas sources for the whole petroleum system in the Jurassic coal-bearing basin. Second, multi-phase shallow braided river delta–shallow lacustrine deposits contribute multiple types of reservoirs, e.g. sandstone, tight sandstone, shale and coal rock, in slope and depression areas, providing effective storage space for the petroleum reservoir formation in coal-measure strata. Third, three phases of hydrocarbon charging and structural evolution, as well as effective configuration of multiple types of reservoirs, result in the sequential accumulation of conventional-unconventional hydrocarbons. From high structural positions to depression, there are conventional structural and structural-lithological reservoirs far from the source, low-saturation structural-lithological reservoirs near the source, and tight sandstone gas, coal rock gas and shale oil accumulations within the source. Typically, the tight sandstone gas and coal rock gas are the key options for further exploration, and the shale oil and gas in the depression area is worth of more attention. The new understanding of the whole petroleum system in the coal measures could further enrich and improve the geological theory of the whole petroleum system, and provide new ideas for the overall exploration of oil and gas resources in the Tuha Basin.

Abstract Direct chemical vapor deposition (CVD) growth of graphene on dielectric/insulating materials is a promising strategy for subsequent transfer-free applications of graphene. However, graphene growth on noncatalytic substrates is faced with thorny issues, especially the limited growth rate, which severely hinders mass production and practical applications. Herein, graphene glass fiber fabric (GGFF) is developed by graphene CVD growth on glass fiber fabric. Dichloromethane is applied as a carbon precursor to accelerate graphene growth, which has a low decomposition energy barrier, and more importantly, the produced high-electronegativity Cl radical can enhance adsorption of active carbon species by Cl–CH2 coadsorption and facilitate H detachment from graphene edges. Consequently, the growth rate is increased by ~3 orders of magnitude and carbon utilization by ~960-fold, compared with conventional methane precursor. The advantageous hierarchical conductive configuration of lightweight, flexible GGFF makes it an ultrasensitive pressure sensor for human motion and physiological monitoring, such as pulse and vocal signals.

Abstract Background Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT. Methods First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre–post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group. Results This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p

Abstract Waste activated sludge (WAS) is attracting attention for its energy and resource potential. Anaerobic digestion (AD) can be used to efficiently recover energy resources and stabilize pollutants in WAS, with biochar emerging as an ideal additive to boost this process. However, the low abundance of surface functional groups and small pore structure of raw biochar may limit its performance in the AD of WAS. These limitations can be overcome by using functional biochar. In this review, the preparation and modification methods for functional biochar and its role in the AD of WAS are systematically summarized and discussed. Notably, the role of functional biochar in electron transfer, buffering effects, microbial immobilization, alleviation of inhibitory effects, and functional microbial modulation are analyzed. Additionally, the impacts of biochar on digestate utilization, pollutant removal, and carbon fixation are discussed. Special attention is given to functional biochar for its ability to promote circular economy and carbon neutrality. Finally, future perspectives on the use of functional biochar in the AD of WAS are presented. The aim of this review is to provide insights into the application of functional biochar in the AD of WAS from the perspective of performance improvement, resource utilization, and circular economy. Graphical Abstract

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. Method Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. Result Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P

Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

In response to the development of the concepts of “carbon neutrality” and “carbon peak”, it is critical to developing materials with high near-infrared (NIR) solar reflectivity and high emissivity in the atmospheric transparency window (ATW; 8–13 μm) to advance zero energy consumption radiative cooling technology. To regulate emission and reflection properties, a series of high-entropy rare earth stannate ceramics (HE-RE2Sn2O7: (Y0.2La0.2Nd0.2Eu0.2Gd0.2)2Sn2O7, (Y0.2La0.2Sm0.2Eu0.2Lu0.2)2Sn2O7, and (Y0.2La0.2Gd0.2Yb0.2Lu0.2)2Sn2O7) with severe lattice distortion were prepared using a solid phase reaction followed by a pressureless sintering method for the first time. Lattice distortion is accomplished by introducing rare earth elements with different cation radii and mass. The as-synthesized HE-RE2Sn2O7 ceramics possess high ATW emissivity (91.38%–95.41%), high NIR solar reflectivity (92.74%–97.62%), low thermal conductivity (1.080–1.619 W·m−1·K−1), and excellent chemical stability. On the one hand, the lattice distortion intensifies the asymmetry of the structural unit to cause a notable alteration in the electric dipole moment, ultimately enlarging the ATW emissivity. On the other hand, by selecting difficult excitation elements, HE-RE2Sn2O7, which has a wide band gap (Eg), exhibits high NIR solar reflectivity. Hence, the multi-component design can effectively enhance radiative cooling ability of HE-RE2Sn2O7 and provide a novel strategy for developing radiative cooling materials.

The proven geological reserves of the Shenfu deep coalbed methane (CBM) field on the eastern margin of the Ordos Basin exceed 100 billion cubic meters. It is of great significance to realizing the efficient development of deep CBM in this region to ensure the national energy supply. However, the complexity of the geological environment which includes high stress, medium-high temperatures, low permeability, strong heterogeneity, and wide developed cleats and natural fractures, makes it challenging for the existed shallow and medium CBM fracturing techniques to be fully applicable to deep CBM resources. As a result, the stimulation scale and parameters for deep coalbed fracturing are still in the trial-and-error stage. In order to explore the stimulation techniques which are compatible with the geological conditions of deep coalbeds, the Shenfu block in the Ordos Basin was taken as the geological background and the large-scale hydraulic fracturing of deep coal seams was conducted as an engineering practice. The authors designed the idea of “Push the limit to the beyond + balanced propagation + effective support”, and proposed the massive hydraulic fracturing techniques based on “multi-stage multi-clusters with moderate-dense cutting + perforation with equal apertures, deep penetration and limited flow + integrated variable viscosity (rock breaking by higher viscous slick water + complex fracture network generating by lower viscous slick water) + high pumping rate with high proppant concentration + pre-acid treatment to reduce the breakdown pressure + graded proppants with multiple sizes to support fractures”. Then, the authors put forward an integrated “Geology-Engineering-AI” workflow to perform post-frac analysis, through double matching and correcting the fracturing pumping pressure and production rate automatically, accurately characterized the stimulated reservoir volume (SRV) and drained rock volume (DRV), and predicted the estimated ultimate recovery (EUR) under different fracturing scales and well types. Finally, by statistically analyzing the gas production characteristics of multiple wells in the Shenfu block and utilizing the random forest method, the primary controlling factors affecting the production capacity of deep CBM were quantitatively analyzed. The results demonstrate that after reservoir stimulation, directional wells can achieve a maximum daily gas production rate exceeding 10 000 m3/d, while horizontal wells can achieve a maximum daily gas production rate exceeding 20 000 m3/d. It indicates that the deep coal beds have good fracturing properties and great development potential. The primary impact factors for peak gas production rate are gas content, coalbed thickness and proppant concentration, while the major impact factors for cumulative gas production include gas content, proppant concentration, and total volume of proppants.

Abstract Assessing the genetic structure of local varieties and understanding their genetic data are crucial for effective management and preservation. However, the genetic differences among local breeds require further explanation. To enhance our understanding of their population structure and genetic diversity, we conducted a genome-wide comparative study of Chaohu and Ji’an Red ducks using genome sequence and restriction site-associated DNA sequencing technology. Our analysis revealed a distinct genetic distinction between the two breeds, leading to divided groups. The phylogenetic tree for Chaohu duck displayed two branches, potentially indicating minimal impact from artificial selection. Additionally, our ROH (runs of homozygosity) analysis revealed that Chaohu ducks had a lower average inbreeding coefficient than Ji’an Red ducks. We identified several genomic regions with high genetic similarity in these indigenous duck breeds. By conducting a selective sweep analysis, we identified 574 candidate genes associated with muscle growth (BMP2, ITGA8, MYLK, and PTCH1), fat deposits (ELOVL1 and HACD2), and pigmentation (ASIP and LOC101797494). These results offer valuable insights for the further enhancement and conservation of Chinese indigenous duck breeds.

Abstract Background HIV self-testing (HIVST) was recommended to improve HIV testing services. China initiated some of the first HIVST pilots in the world, providing a unique opportunity for implementation research. We aim to investigate HIVST adoption and its following linkage to care among Chinese men who have sex with men (MSM). Methods Data were collected using an online questionnaire distributed on major social media platforms in 2018, one year after HIVST was officially endorsed and allowed for sale. MSM who were at least 16 years old, assigned as male at birth, and ever tested for HIV were eligible. Primary outcome, adoption was defined as ever use of HIVST. Bivariate and multivariable logistic regressions were performed to explore the association between HIVST adoption and sociodemographic and behavioral factors. Linkage to care was also described via the following sequential events as indicators: (1) receiving result after recent test (2), seeking care from healthcare facility if test result was positive or indeterminate, and (3) delayed time before seeking care. Results A total of 540 participants were included with an average age of 27.4 ± 6.6. Most were never married (87.4%) and half completed college (52.2%). Overall, 75.2% had adopted HIVST. Self-test kits were commonly obtained from community-based organizations (54.4%) and from online (46.6%). HIVST adoption was positively associated with having college or higher education (OR = 1.66, 95%CI: 1.07–2.57), and negatively associated with age older than 30 (AOR = 0.52, 95%CI: 0.32–0.84). Adoption was not associated with other socio-demographic or behavioral factors. After receiving HIV-positive or indeterminate results, 25/25 of HIVST adopters sought care while 3 out of 7 (42.9%) non-adopters sought care (p

Abstract Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

Abstract Previous reports have established that rESWT fosters angiogenesis, yet the mechanism by which rESWT promotes cerebral angiogenesis remains elusive. rESWT stimulated HUVECs proliferation as evidenced by the CCK-8 test, with an optimal dosage of 2.0 Bar, 200 impulses, and 2 Hz. The tube formation assay of HUVECs revealed that tube formation peaked at 36 h post-rESWT treatment, concurrent with the lowest expression level of Bach1, as detected by both Western blot and immunofluorescence. The expression level of Wnt3a, β-catenin, and VEGF also peaked at 36 h. A Bach1 overexpression plasmid was transfected into HUVECs, resulting in a decreased expression level of Wnt3a, β-catenin, and VEGF. Upon treatment with rESWT, the down-regulation of Wnt3a, β-catenin, and VEGF expression in the transfected cells was reversed. The Wnt/β-catenin inhibitor DKK-1 was utilized to suppress Wnt3a and β-catenin expression, which led to a concurrent decrease in VEGF expression. However, rESWT treatment could restore the expression of these three proteins, even in the presence of DKK-1. Moreover, in the established OGD model, it was observed that rESWT could inhibit the overexpression of Bach1 and enhance VEGF and VEGFR-2 expression under the OGD environment.

Abstract In rural China, the aging population faces unique challenges that affect their life satisfaction. These challenges are compounded by disparities in access to resources compared to urban areas, making it crucial to address these issues to ensure a dignified and fulfilling later life. Understanding and improving life satisfaction for this demographic is essential, not only for the well-being of the elderly but also for the overall social stability and economic sustainability of these communities. Using a rural sample from the Chinese Social Survey (CSS), this study investigates the interplay between social quality factors and life satisfaction among older adults in rural China. It focuses on the roles of socioeconomic security, social cohesion, social inclusion, and social empowerment in shaping the well-being of this demographic. It was found that the four conditional factors of social quality—socioeconomic security, social cohesion, social inclusion, and social empowerment—have different influences on life satisfaction among older adults in rural areas. The statistical model shows that the influence of absolute family income on social and economic security does not have statistical significance. In contrast, housing, pension insurance participation, and public safety perception positively affect life satisfaction among older adults in rural areas. Among the social cohesion factors, higher social morality, legal system evaluation, social identity, grassroots government, and interpersonal trust contribute to the life satisfaction of older adults in rural areas. Regarding social inclusion factors, good social tolerance, social equity, and perception of government public services can significantly improve life satisfaction among older adults in rural areas. For social empowerment factors, social participation helps expand the social support network of older adults in rural areas, enhancing their life satisfaction. Paths to improving the quality of rural society should be explored to improve relative poverty in rural areas. They should continue to be pursued to strengthen the old-age security system for older adults in rural areas. Further, the National Medium- and Long-Term Plan for Actively Responding to Population Aging should be the base for forming an elderly-friendly society. A good atmosphere promotes the participation of people, families, and society; supports social cohesion; enhances inclusion; and promotes social participation, improving life satisfaction.

Abstract Nano-switch structures are important control elements in nanoelectromechanical systems and have potential applications in future nanodevices. This paper analyzes the effects of surface effects, geometric nonlinearity, electrostatic forces, and intermolecular forces on the nonlinear bending behavior and adhesion stability of nano-switches. Based on the Von Karman geometric nonlinearity theory, four types of boundary conditions for the nano-switch structure were specifically calculated. The results show that surface effects have a significant impact on the nonlinear bending and adhesion stability of nano-switches. Surface effects increase the adhesion voltage of the nano-switch and decrease its adhesion displacement, and as the size of the nano-switch structure increases, the impact of surface effects decreases. A comparative analysis of the linear theory and the nonlinear theory results shows that the adhesion voltage predicted by the linear theory is smaller than that predicted by the nonlinear theory. The effect of geometric nonlinearity increases as the size of the nano-switch structure increases, as the distance between the electrodes increases, and as the aspect ratio of the nano-switch structure increases. These findings provide theoretical support and reference for the design and use of future nanodevices and nanoelectromechanical systems.

Ultra-fine grained magnesium alloys are usually prepared by severe deformation and medium-low temperature deformation. In this work, it has been found that the binary Mg-1.2Ce alloy with the uniform distributed Mg12Ce precipitates smaller than 3 μm is a good candidate to obtain ultra-fine grains by conventional one-step extrusion at high temperatures. All the three Mg-1.2Ce samples extruded at 300 °C, 350 °C and 400 °C show a bimodal microstructure with high-density dislocations, whose average grain sizes are 1.19 ± 0.92 μm, 1.32 ± 1.30 μm, and 1.44 ± 1.33 μm, respectively. A linear relation of ln(d) = -0.05ln(Z)+1.27 was determined relating the average grain size (d) to the Zener-Hollomon parameter (Z). The alloy extruded at 300 °C exhibits an exceptionally high ultimate tensile strength (UTS) of 412.3 ± 5.3 MPa and yield strength (TYS) of 387.6 ± 3.2 MPa, but a low elongation after fracture (El) of 4.9 ± 0.8 %. With the extrusion temperature increasing, the tensile strength gradually decreases. For the 1.2E-400 sample, the TYS and the UTS drop to 347.2 ± 2.1 MPa and 349.4 ± 2.8 MPa, while the El increases to a more acceptable value of 12.6 ± 1.4 %. The microstructure analysis reveals that Ce atoms segregate along grain boundaries and dislocations in the Mg-1.2Ce alloy, which can limit the gliding of GBs or the slipping and climbing of dislocations. Additionally, dislocations can be pinned by Mg12Ce precipitates, thereby also restricting dislocation and grain boundary mobility. Consequently, the dynamic recrystallization (DRX) process is delayed, leading to the formation of a bimodal microstructure.

Abstract Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Abstract Background This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. Methods This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. Results A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P

Abstract Hydrogen-bonded organic frameworks (HOFs) are versatile materials with potential applications in proton conduction. Traditional approaches involve incorporating humidity control to address grain boundary challenges for proton conduction. This study finds vitrification as an alternative strategy to eliminate grain boundary effect in HOFs by rapidly melt quenching the kinetically stable HOF-SXU-8 to glassy state HOF-g. Notably, a remarkable enhancement in proton conductivity without humidity was achieved after vitrification, from 1.31 × 10−7 S cm−1 to 5.62× 10−2 S cm−1 at 100 °C. Long term stability test showed negligible performance degradation, and even at 30 °C, the proton conductivity remained at high level of 1.2 × 10−2 S cm−1. Molecule dynamics (MD) simulations and X-ray total scattering experiments reveal the HOF-g system is consisted of three kinds of clusters, i.e., 1,5-Naphthalenedisulfonic acid (1,5-NSA) anion clusters, N,N-dimethylformamide (DMF) molecule clusters, and H+-H2O clusters. In which, the H+ plays an important role to bridge these clusters and the high conductivity is mainly related to the H+ on H3O+. These findings provide valuable insights for optimizing HOFs, enabling efficient proton conduction, and advancing energy conversion and storage devices.

Abstract The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Abstract Herein, the feasibility of artificial black soil (ABS) derived from hydrothermal humification-hydrothermal carbonization (HTH-HTC) for restructuration of weak soil was verified. This study breaks through the long history of soil formation and evolution, and obtains reconstructed anthropogenic soil (AS) system which only takes one month, for the further application of rice seedlings. HTH-HTC derived by-products are slightly acidic, which facilitates the effective nutrient uptake and prevention of wilt diseases for acid-loving rice seedlings. AS mainly consists of the inherent components retained from weak soil such as SiO2 and minerals, and exogenous components such as artificial humic substances and hydrochar, as introduced by hydrothermal humification processes. Results exhibit that AS has high contents of ammonium nitrogen, organic matter, organic carbon, and abundant porous structure for nutrient transport and water holding, especially, the community diversity and richness of microbial system gets the expected recovery and new beneficial bacteria (such as Caballeronia calidae) or fungi (such as Humicola) appear. Positive effects of AS on agronomic traits in rice seedlings are quantified. As a general result, this study supports the application of AS in sustainable agriculture, and provides a novel strategy to tackle the already-omnipresent land degradation by anthropogenic misuse and larger scale accidents.

Background/Aims Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.

20CrMnTi steel is widely used in the gear manufacturing field of engineering machinery. The addition of Ti element to steel can effectively improve its low-temperature impact toughness and enhance its mechanical properties. However, during the smelting process of 20CrMnTi, large-sized TiN inclusions are inevitably formed in the steel, which affects its service performance improvement. This paper focuses on the directional modification behaviors of TiN inclusions in 20CrMnTi gear steel by rare earth Ce under deoxygenation conditions of Si–Ca–Ba alloy. The results show that under the deoxygenation conditions of Si–Ca–Ba alone, there are composite inclusions in 20CrMnTi steel with CaAl12O19 as the core and TiN wrapped around the periphery, all of which have sizes greater than 2 μm. This type of inclusion is square or diamond shaped, and the addition of Si–Ca–Ba deoxygenation alone has poor TiN modification effect on gear steel 20CrMnTi. Adding Ce element can effectively improve the nucleation core of inclusions. The CeAlO3–TiN and (CaAl12O19–Ba–Ce)–TiN composite inclusions are formed, and the TiN inclusions are modified in terms of morphology and size. The average size of inclusions decreases from 4.1 to 3.0 μm, which prevented the excessive growth of pure TiN inclusions to some extent.

The inferior creep ductility of Inconel 718 (IN718) fabricated by selective laser melting (SLM), which is unable to meet aerospace material specification (≥4%), limits its engineering application. Despite persistent optimization efforts in the SLM process and post-heat treatment, this issue remains unresolved. This study involved SLM fabrication of the modified IN718 with trace amounts of LaB6 and/or P, followed by homogenization and double aging heat treatment. The addition of trace LaB6 notably influenced the recrystallized grain structure and carbide precipitation at grain boundaries, while trace P addition had minimal impact. All samples exhibited similar γ′ and γ″ strengthening precipitates. Creep tests conducted at 650°C/690 MPa revealed that the individual modification of LaB6 showed limited improvement in creep performance and P showed no improvement, but the combined addition of LaB6 and P led to a substantial enhancement in creep performance, especially reaching as high as 8.6% creep strain. This remarkable improvement in creep ductility is unlikely to arise from the altered grain structure and grain boundary precipitates induced by LaB6 but predominantly arises from the synergistic effect of P and B in enhancing resistance to crack propagation during the third stage of creep.