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Abstract Background Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. However, the optimal injection timing of PEG-rhG-CSF after chemotherapy is obscure. The trial was designed to explore the best administration timing of PEG-rhG-CSF when breast cancer patients could benefit most. Methods Patients with early breast cancer were randomly assigned to receive a preventive injection on the 7th or 3rd day following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n = 80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN in the first cycle was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction. Results In comparison to the control group, the experimental group exhibited higher white blood cell count (WBC) and absolute neutrophil count (ANC) on the 9th and 13th days following chemotherapy (P

Abstract The membrane electrode assembly (MEA) is promising for practical applications of the electrocatalytic CO2 reduction reaction (CO2RR) to multi-carbon (C2+) compounds. Water management is crucial in the MEA electrolyser without catholyte, but few studies have clarified whether the co-feeding water in cathode can enhance C2+ formation. Here, we report our discovery of pivotal roles of a suitable nanocomposite electrocatalyst with abundant Cu2O−Cu0 interfaces in accomplishing water-promoting effect on C2+ formation, achieving a current density of 1.0 A cm−2 and a 19% single-pass C2+ yield at 80% C2+ Faradaic efficiency in MEA. The operando characterizations confirm the co-existence of Cu+ with Cu0 during CO2RR at ampere-level current densities. Our studies reveal that Cu+ works for water activation and aids C‒C coupling by enhancing formations of adsorbed CO and CHO species. This work offers a strategy to boost CO2RR to C2+ compounds in industrial-relevant MEA by combining water management and electrocatalyst design.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use. Method PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models. Results After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score. Conclusion Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

Titanium alloy is a typically difficult-to-process material, and its surface state significantly impacts its applications in aerospace, ships, and other fields. To obtain high-quality surface, laser surface melting and electrochemical polishing (LSM-ECP) combined processing was presented to polish Ti6Al4V in this study. The effects of laser surface melting (LSM) on the electrochemical polishing (ECP) surface morphology and properties of Ti6Al4V alloy (LSM-ECP) was studied. The research includes microstructure evolution, surface phase and element change, microhardness, and surface corrosion resistance. The results showed that the LSM-ECP surface roughness was further reduced by 73.8%–168 nm. LSM-ECP can partially remove the remelted layer, and the generated metal oxides such as TiO2, Ti2O3, TiO, Al2O3. and other metal oxides help protect the surface of the specimen, reduce corrosion, and the surface hardness and corrosion resistance of the substrate was improved. It can be concluded that grain refinement, a large number of needle-shaped α′+β phases and dislocatiaon in the LSM Ti6Al4V alloy can provide more numbers of corrosion of grain boundaries, the oxide layer and low roughness during the ECP process. The electrode response of LSM-ECP is faster than that of direct ECP of the substrate surface, better polishing result is obtained in a shorter time.

This study utilized Al–Zn–Mg–Cu alloy chips as raw materials to prepare recycled billets through a solid-state recycling process. Isothermal hot compression tests were conducted using a thermal simulation machine to establish an Arrhenius-type constitutive equation and the hot processing map based on the dynamic materials model. The microstructure of the recycled Al–Zn–Mg–Cu alloy after hot compression was characterized and analyzed using SEM, EBSD, and TEM, exploring the microstructural evolution mechanisms of the recycled alloy at different temperatures and strain rates. The results indicate that the optimal hot deformation parameters for the recycled Al–Zn–Mg–Cu alloy are 300–360 °C at a strain rate of 0.01–0.05 s⁻1 and 400–450 °C at a strain rate of 0.05–0.3 s⁻1. At the same strain rate, as the deformation temperature increases, low-angle grain boundaries gradually disappear, and the grain structure becomes more stable. Dynamic recrystallization replaces dynamic recovery as the dominant mechanism. At the same deformation temperature, low strain rates allow more time for the migration of low-angle grain boundaries, thereby promoting the growth of dynamically recrystallized grains and ultimately forming new, undistorted grains.

Abstract Background Neonatal respiratory distress syndrome (NRDS) is harmful to neonates and the prognosis is variable, ranging from mild to severe forms. This study aims to evaluate the clinical utility of miR-513a-3p in conjunction with arterial blood gas analysis parameters and lung ultrasound (LUS) score in the context of NRDS. Methods The study included 169 preterm infants, including 106 newborns with NRDS and 63 newborns without NRDS. The relative expression level of miR-513a-3p was detected by quantitative real time polymerase chain reaction (qRT-PCR). Umbilical artery blood gas parameter values and LUS score were recorded, and the clinical significance of miR-513a-3p, umbilical artery blood gas parameter and LUS score in NRDS were evaluated by Receiver Operating Characteristic (ROC) analysis. Results Elevated levels of miR-513a-3p were detected in the serum of NRDS, and higher expression of miR-513a-3p was observed in individuals with poor prognosis. Notably, miR-513a-3p exhibited a significant correlation with the parameters of arterial blood gas analysis and LUS score in NRDS patients. Furthermore, miR-513a-3p was one of the risk factors for poor prognosis in NRDS patients. miR-513a-3p levels combined with umbilical artery blood gas parameters and LUS score has diagnostic value for NRDS and is reliable for its prognosis. Conclusions Elevated levels of miR-513a-3p in neonatal serum served as a useful tool in the combined assessment with umbilical artery blood gas analysis and LUS score to diagnosis and prognosis of NRDS. Consequently, miR-513a-3p may be served as a biomarker for diagnosis and prognosis of NRDS.

Abstract Background Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5–10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. Methods Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. Results Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5–10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. Conclusions Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. Trial registration: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic.clinicaltrials.gov/ct2/show/NCT05432128 .

Abstract The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

The germination process of seeds is influenced by the interplay between two opposing factors, pectin methylesterase (PME) and pectin methylesterase inhibitor (PMEI), which collectively regulate patterns of pectin methylesterification. Despite the recognized importance of pectin methylesterification in seed germination, the specific mechanisms that govern this process remain unclear. In this study, we demonstrated that the overexpression of GhPMEI53 is associated with a decrease in PME activity and an increase in pectin methylesterification. This leads to seed cell wall softening, which positively regulates cotton seed germination. AtPMEI19, the homologue in Arabidopsis thaliana, plays a similar role in seed germination to GhPMEI53, indicating a conserved function and mechanism of PMEI in seed germination regulation. Further studies revealed that GhPMEI53 and AtPMEI19 directly contribute to promoting radicle protrusion and seed germination by inducing cell wall softening and reducing mechanical strength. Additionally, the pathways of abscicic acid (ABA) and gibberellin (GA) in the transgenic materials showed significant changes, suggesting that GhPMEI53/AtPMEI19-mediated pectin methylesterification serves as a regulatory signal for the related phytohormones involved in seed germination. In summary, GhPMEI53 and its homologs alter the mechanical properties of cell walls, which influence the mechanical resistance of the endosperm or testa. Moreover, they impact cellular phytohormone pathways (e.g., ABA and GA) to regulate seed germination. These findings enhance our understanding of pectin methylesterification in cellular morphological dynamics and signaling transduction, and contribute to a more comprehensive understanding of the PME/PMEI gene superfamily in plants.

Objective: Cancer survivors have experienced subjective cognitive impairment (SCI) when they received cancer diagnoses or treatments. Their psychosocial and emotional statuses were also impacted. With the advancement of web technologies, web-based cognitive interventions have been implemented in the management and the alleviation of the SCI, the psychosocial distress, and the emotional distress in cancer survivors. This review aimed to summarize the intervention contents of web-based cognitive interventions for SCI, and to explore the effects of the interventions on SCI, psychosocial status, and emotional health. Methods: Six databases (CINAHL Plus, Cochrane Library, Embase, APA PsycInfo, PubMed and CNKI) were searched from the establishment of databases up to December 2023. Literature references were also manually searched for related articles. Results: This review contained 21 studies that covered the contents of web-based cognitive interventions, such as computer-assisted cognitive training, online cognitive rehabilitation, cognitive behavior therapy with the Internet, telehealth physical exercise, and web-based mindfulness interventions. The effects of web-based cognitive interventions positively impacted SCI for cancer survivors. Also, these interventions showed varying degrees of effectiveness in alleviating psychosocial and emotional distresses. Conclusion: By summarizing five types of cognitive intervention contents delivered via web technology, this review demonstrated that web-based cognitive interventions optimized SCI and overall psychosocial and emotional statuses for the cancer survivors. It is recommended that future research focus on the development of customized web-based cognitive interventions for individuals with SCI, along with their psychosocial and emotional statuses.

Abstract Fritillaria cirrhosa, an endangered medicinal plant in the Qinghai-Tibet Plateau, is facing resource scarcity. Artificial cultivation has been employed to address this issue, but problems related to continuous cultivation hinder successful transplantation. Imbalanced microbial communities are considered a potential cause, yet the overall changes in the microbial community under continuous cropping systems remain poorly understood. Here, we investigated the effects of varying durations of continuous cropping on the bacterial and fungal communities, as well as enzymatic activities, in the rhizospheric soil of F. cirrhosa. Our findings revealed that continuous cropping of F. cirrhosa resulted in soil acidification, nutrient imbalances, and increased enzyme activity. Specifically, after 10 years of continuous cropping, there was a notable shift in the abundance and diversity (e.g., Chao1 index) of soil bacteria and fungi. Moreover, microbial composition analyses revealed a significant accumulation of harmful microorganisms associated with soil-borne diseases (e.g., Luteimonas, Parastagonospora, Pseudogymnoascus) in successively cropped soils, in contrast to the significant reduction of beneficial microorganisms (e.g., Sphingomonas, Lysobacter, Cladosporium) that promote plant growth and development and protect against diseases such as Fusarium sp.These changes led to decreased connectivity and stability within the soil microbial community. Structural equation modeling and redundancy analysis revealed that alkaline hydrolytic nitrogen and available phosphorus directly influenced soil pH, which was identified as the primary driver of soil microbial community changes and subsequently contributed to soil health deterioration. Overall, our results highlight that soil acidification and imbalanced rhizosphere microbial communities are the primary challenges associated with continuous cropping of F. cirrhosa. These findings establish a theoretical foundation for standardized cultivation practices of F. cirrhosa and the bioremediation of continuously cultivated soils.

Abstract Realizing an efficient turnover frequency in the acidic oxygen evolution reaction by modifying the reaction configuration is crucial in designing high-performance single-atom catalysts. Here, we report a “single atom–double site” concept, which involves an activatable inert manganese atom redox chemistry in a single-atom Ru-Mn dual-site platform with tunnel Ni ions as the trigger. In contrast to conventional single-atom catalysts, the proposed configuration allows direct intramolecular oxygen coupling driven by the Ni ions intercalation effect, bypassing the secondary deprotonation step instead of the kinetically sluggish adsorbate evolution mechanism. The strong bonding of Ni ions activates the inert manganese terminal groups and inhibits the cross-site disproportionation process inherent in the Mn scaffolding, which is crucial to ensure the dual-site platform. As a result, the single-atom Ru-Ni-Mn octahedral molecular sieves catalyst delivers a low overpotential, adequate mass activity and good stability.

Abstract Electrosynthesis of adipic acid (a precursor for nylon-66) from KA oil (a mixture of cyclohexanone and cyclohexanol) represents a sustainable strategy to replace conventional method that requires harsh conditions. However, its industrial possibility is greatly restricted by the low current density and competitive oxygen evolution reaction. Herein, we modify nickel layered double hydroxide with vanadium to promote current density and maintain high faradaic efficiency (>80%) within a wide potential window (1.5 ~ 1.9 V vs. reversible hydrogen electrode). Experimental and theoretical studies reveal two key roles of V modification, including accelerating catalyst reconstruction and strengthening cyclohexanone adsorption. As a proof-of-the-concept, we construct a membrane electrode assembly, producing adipic acid with high faradaic efficiency (82%) and productivity (1536 μmol cm−2 h−1) at industrially relevant current density (300 mA cm−2), while achieving >50 hours stability. This work demonstrates an efficient catalyst for adipic acid electrosynthesis with high productivity that shows industrial potential.

Abstract DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ’s activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L’s S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.

Abstract This study explores the association between LE8 scores and mortality risks among individuals diagnosed with cardiovascular disease (CVD). Utilizing data from the NHANES conducted between 2005 and 2018, survey-weighted multivariable Cox proportional hazards regression models were utilized. Life’s Essential 8 (LE8) scores dose–response associations were assessed using restricted cubic spline regression. Sub-analyses were performed for different categories of CVD. The study consisted of 2164 participants diagnosed with CVD, ranging in age from 20 to 80 years (weighted mean [SE] age, 61.47 [0.34] years; The average total LE8 was 64.97 [0.54]. 499 participants experienced mortality, with 350 deaths attributed to CVD. After accounting for potential covariates, LE8 score was found to be associated with a decreased both all-cause mortality (OR 0.34, CI 0.22–0.51) and CVD mortality (OR 0.40, CI 0.23–0.68). A survey-weighted multivariable Cox model with restricted cubic splines identified the lowest all-cause mortality (P

Enhancing the thermal shock resistance of Y2O3 ceramic crucibles, coupled with advancements in melting and casting technologies to reduce the adverse influence of interfacial reactions, is essential for producing low-energy consumption, high-quality titanium-aluminum (TiAl) alloys. In this study, the Y2O3 ceramic crucible with good thermal shock resistance was developed through the optimization of particle size distribution and sintering holding time. The interaction mechanisms between Y2O3 ceramics and TiAl alloys under extreme conditions were investigated, and strategies for enhancing the mechanical properties of TiAl alloys through the integration of Y2O3 crucibles with centrifugal casting were discussed. The results indicated that introducing large particles of 1–3 mm under sintering conditions of 2023 K and 6 h effectively enhances the thermal shock resistance of Y2O3 crucible. The interaction between Y2O3 and TiAl alloys primarily involved physical erosion (spalling/dispersion), dissolution of separated particles, and surface modification of interface layer particles (reaction). Physical erosion played an important role in this dynamic interaction, with the extent of erosion intensifying through continuous use of the crucible, while electromagnetic forces ensured the uniform distribution of inclusions within the TiAl alloy matrix. Moreover, the application of centrifugal casting technology substantially refines the grain size and reduces the inclusion count, thereby significantly enhancing the mechanical properties of TiAl alloy.

Abstract Background The study aimed to evaluate the diagnostic efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) parameters in distinguishing sinonasal lymphoma from sinonasal carcinoma. Methods Forty-two participants with histologically confirmed sinonasal lymphomas and fifty-two cases of sinonasal carcinoma underwent imaging with a 3.0T MRI scanner. DCE-MRI and DWI were conducted, and various parameters including type of time-intensity curve(TIC), time to peak, peak enhancement, peak contrast enhancement, washout rate, apparent diffusion coefficient (ADC), and relative ADC were measured. Binary logistic regression and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic capability of individual and combined indices for differentiating nasal sinus lymphoma from nasal sinus carcinoma. Results Sinonasal lymphoma predominantly exhibited type II TIC(n = 20), whereas sinonasal carcinoma predominantly exhibited type III TIC(n = 23). Significant differences were observed in all parameters except washout ratio (p

Abstract Objectives This study pursued two main purposes. The first aim was to expound on the microscopic factors of radiation-related caries (RRC). Further, it aimed to compare the remineralization effect of different remineralizing agents on demineralized teeth after radiotherapy. Methods The enamel and dentin samples of bovine teeth were irradiated with different doses of radiation. After analysis of scanning electron microscope (SEM), X-Ray diffraction (XRD), and energy dispersive spectrometer (EDS), the samples irradiated with 50 Gy radiation were selected and divided into the demineralization group, the double distilled water (DDW) group, the Sodium fluoride (NaF) group, the Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) group, the NaF + CPP-ACP group, and the Titanium tetrafluoride (TiF4) group. After demineralization, remineralizing agents treatment, and remineralization, the samples were evaluated using SEM, atomic force microscope (AFM), EDS, and transverse microradiography (TMR). Results A radiation dose of 30 Gy was sufficient to cause damage to the dentinal tubules, but 70 Gy radiation had little effect on the microstructure of enamel. Additionally, the NaF + CPP-ACP group and the TiF4 group significantly promoted deposit formation, decreased surface roughness, and reduced mineral loss and lesion depth of demineralized enamel and dentin samples after radiation. Conclusions Radiation causes more significant damage to dentin compared to enamel. NaF + CPP-ACP and TiF4 had a promising ability to promote remineralization of irradiated dental hard tissues. Advances in knowledge This in vitro study contributes to determining a safer radiation dose range for teeth and identifying the most effective remineralization approach for RRC.

Improving the anticorrosion property of Mg alloys used as concrete formwork is essential for extending their lifespan and ensuring structural integrity. Therefore, MgCO3·3H2O + MgCO3·Mg(OH)2·3H2O/MgO composite coating was prepared on AZ41 Mg alloys using an ultrasonic-cavitated chemical conversion method under different pH conditions. Electrochemical methods combined with immersion tests in the simulated concrete pore solutions containing 0.6 M NaCl were adopted to assess the anticorrosion performance of the uncoated and coated specimens. Results indicate that the improved pH benefits the densification of the composite coating, thus leading to the enhanced anticorrosion performance. The generation of dense MgCO3·Mg(OH)2·3H2O layer rather than corrosion products after immersion makes such an affordable anticorrosion coating, amenable to large-scale production, holds promise as a viable surface treatment method for Mg alloy concrete formwork.

Abstract Background Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. Methods The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague–Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. Results The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. Conclusion NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

In this study, Mg-13.2Gd-4.3Ni alloys containing continuous bulk-shaped long-period stacking ordered (LPSO), lamellar LPSO, and a small amount of eutectic phase were prepared, and the evolution of microstructure at different extrusion temperatures and its influence on mechanical and degradation properties as well as corrosion mechanism were investigated. Preheating before extrusion can effectively promote the precipitation of lamellar LPSO in matrix. EX400 with higher volume fraction of non-DRXed grains exhibited higher strength, which was mainly due to strong texture, high dislocation density, and high volume fraction of lamellar LPSO. The EX420 with higher volume fraction of DRXed grains showed higher degradation rate, which was mainly due to the higher density of grain boundary. The EX400 exhibited excellent comprehensive properties with tensile yield strength (TYS) of 334 MPa, ultimate tensile strength (UTS) of 484 MPa and elongation (EL) of 7.4%, ultimate compressive strength (UCS) of 638 MPa and compressive yield strength (CYS) of 443 MPa, degradation rate of 86.1 mg/cm2/h at 93 °C in 3 wt.% KCl solution.

Nitrogen dioxide (NO2) is a prevalent air pollutant in urban areas, originating from outdoor sources, household gas consumption, and secondhand smoke. The limited evaluation of the disease burden attributable to NO2, encompassing different health effects and contributions from various sources, impedes our understanding from a public health perspective. Based on modeled NO2 exposure concentrations, their exposure–response relationships with lung cancer, chronic obstructive pulmonary disease, and diabetes mellitus, and baseline disability-adjusted life years (DALYs), we estimated that 1,675 (655–2,624) thousand DALYs were attributable to NO2 in urban China in 2019 [138 (54–216) billion Chinese yuan (CNY) economic losses]. The transition from gas to electricity for household cooking was estimated to reduce the attributable economic losses by 35%. This reduction falls within the range of reductions achieved when outdoor air meets the World Health Organization interim target 3 and air quality guidelines for annual NO2, highlighting the significance of raising awareness of gas as a polluting household energy for cooking. These findings align with global sustainable development initiatives, providing a sustainable solution to promote public health while potentially mitigating climate change.

Abstract Background Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Abstract Background Dysregulation of zinc homeostasis is widely recognized as a hallmark feature of prostate cancer (PCa) based on the compelling clinical and experimental evidence. Nevertheless, the implications of zinc dyshomeostasis in PCa remains largely unexplored. Methods In this research, the zinc homeostasis pattern subtype (ZHPS) was constructed according to the profile of zinc homeostasis genes. The identified subtypes were assessed for their immune functions, mutational landscapes, biological peculiarities and drug susceptibility. Subsequently, we developed the optimal signature, known as the zinc homeostasis-related risk score (ZHRRS), using the approach won out in multifariously machine learning algorithms. Eventually, clinical specimens, Bayesian network inference and single-cell sequencing were used to excavate the underlying mechanisms of MT1A in PCa. Results The zinc dyshomeostasis subgroup, ZHPS2, possessed a markedly worse prognosis than ZHPS1. Moreover, ZHPS2 demonstrated a more conspicuous genomic instability and better therapeutic responses to docetaxel and olaparib than ZHPS1. Compared with traditional clinicopathological characteristics and 35 published signatures, ZHRRS displayed a significantly improved accuracy in prognosis prediction. The diagnostic value of MT1A in PCa was substantiated through analysis of clinical samples. Additionally, we inferred and established the regulatory network of MT1A to elucidate its biological mechanisms. Conclusions The ZHPS classifier and ZHRRS model hold great potential as clinical applications for improving outcomes of PCa patients.

Fermented milk has a long history of being fermented by lactic acid bacteria. Fermented milk contains many elements, including protein, minerals, and vitamins. Fermented milk is gaining more and more attention from customers as people’s desire for a high quality of life improves. Most of the fermented milk on the market today are prepared with single strains or traditional lactic acid bacteria (Streptococcus thermophilus and Lactobacillus bulgaricus) as fermenting agents. However, this production method results in issues like an excessively long fermentation time, a mildly inferior taste, and poor stability. Compound strains have recently gained attention in the field of fermented milk preparation. By utilizing interactions and synergies between various strains, it is possible to increase the quantity and diversity of metabolites, enhancing the quality and functional properties of fermented milk and compensating for some of the shortcomings of conventional fermented milk in terms of product morphology and sensory experience. This study examines how complexing strains have accelerated pH reduction, improved the product’s sensory qualities, rheological characteristics, and water-holding capacity, as well as increased their capacity for lipid-lowering, anti-inflammatory, antioxidant, and bacteriostatic effects. Finally, the future research paths for fermented milk innovation are intended to offer suggestions for the diverse, functionalized, and precise production of fermented milk.

During the Omicron pandemic in late 2022, this study surveyed Chinese students via an online questionnaire to assess their mental health status, prevalence of psychological symptoms, and associated factors. A nationwide cross-sectional survey of 4254 participants was conducted in seven regions of China from January 5 to February 9, 2023. Scales were utilized respectively to measure depressive symptoms, anxiety symptoms, post-traumatic stress disorder (PTSD) symptoms, and perceived social support. Descriptive, univariate, and multivariable analyses were performed to identify associated factors. Protective factors against depressive symptoms include regular exercise and robust social support networks, while risk factors involve excessive alcohol consumption, comorbidities, Omicron infection, and irregular sleep patterns. Risk factors for anxiety symptoms include comorbidities, Omicron infection, living alone, and irregular sleep patterns, while social support emerges as a protective factor. For PTSD symptoms, regular exercise and strong social support systems are identified as protective measures, with risks associated with comorbidities, Omicron infection, and poor sleep quality. Students are particularly vulnerable during the pandemic due to their lifestyle and academic pressures. It's essential to bolster their social support and promote healthier habits.

Magnetic Resonance Imaging (MRI) is a globally acknowledged diagnostic procedure particularly recognized for its superior soft tissue contrast, high-resolution imaging, and non-ionizing radiation properties, making it an indispensable tool in the medical field. However, to optimize MRI’s sensitivity and specificity towards certain diseases, use of contrast agents becomes necessary. Recent developments focus on nanomaterial-based MRI contrast agents to improve diagnostic accuracy and image quality. This review highlights advancements in such agents, including metal oxide nanoparticles, carbon-based materials, gold nanoparticles, and quantum dots. It discusses their roles in MRI-guided therapies like targeted drug delivery, hyperthermia, radiation therapy, photodynamic therapy, immunity-boosting therapy, and gene therapy. Insights into the future potential of MRI contrast agents in imaging medicine are also provided.

To enhance the thermal efficiency of self-cooling oil-immersed transformers in high-temperature environments, this study proposes a method to improve heat transfer by disrupting the boundary layer through incorporating a V-shaped raised structure on the inner wall of the transformer. Numerical calculations using COMSOL software were conducted to compare and analyze the effects of four distinct geometric shapes of protrusions on the thermal performance of 35 kV self-cooling oil-immersed transformers. The results demonstrate that among these four structures, the cone-shaped raised structure exhibits optimal heat dissipation effect and effectively mitigates winding operating temperature. Building upon this finding, response surface methodology was employed for experimental design, constructing a response surface model with minimum winding operating temperature as an objective function while considering variables such as longitudinal spacing (P), height (e), and transverse spacing (g) of cone-shaped protrusions. Through analysis, optimal geometric parameters for cone-shaped raised structures were determined. This research provides an effective solution to address energy consumption and low efficiency issues prevalent in traditional oil-immersed radiators.

Summary: Generative design of promoters has enhanced the efficiency of de novo creation of functional sequences. Though several deep generative models have been employed in biological sequence generation, including variational autoencoder (VAE) or Wasserstein generative adversarial network (WGAN), these models might struggle with mode collapse and low sample diversity. In this study, we introduce the multinomial diffusion model (MDM) for promoter sequence design and propose a structured set of criteria for effectively comparing the performance of generative models. In silico experiments demonstrate that MDM outperforms existing generative AI approaches. MDM demonstrates superior performance in various computational evaluations, remains robust during the training process, and exhibits a strong ability in capturing weak signals. In addition, we experimentally validated that the majority of our model designed promoters have expression activities in vivo, indicating the practicality and potential of MDM for bioengineering.

Purpose: To investigate anatomical and dosimetric changes during volumetric modulated arc therapy (VMAT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) after induction therapy (IT) and explore characteristics of patients with notable variations. Materials and methods: From July 2021 to June 2023, 60 LA-NPC patients undergoing VMAT after IT were retrospectively recruited. Adaptive computed tomography (aCT), reconstructed from weekly cone-beam computed tomography(CBCT), facilitates recontouring and planning transplantation. Volume, dice similarity coefficients, and dose to target volumes and organs at risk(OARs) on planning CT(pCT) and aCT were compared to identify changing patterns. Multivariate logistic regression was used to investigate risk factors. Results: The volumes of PGTVnasopharynx (PGTVp), PGTVnode (PGTVn), ipsilateral and contralateral parotid glands decreased during VMAT, with reductions of 2.25 %, 6.98 %, 20.09 % and 18.00 %, respectively, at 30 fractions from baseline (P

Adipose tissue is traditionally classified into two main types based on their functions: brown adipose tissue (BAT) and white adipose tissue (WAT). Each type plays a distinct role in the body's energy metabolism. Additionally, a third type, beige adipose tissue, can develop within subcutaneous WAT (including inguinal WAT, iWAT) in response to specific stimuli and exhibits characteristics of both BAT and WAT. Extracellular vesicles (EVs) are crucial for intercellular communication, carrying a diverse array of biomolecules such as proteins, lipids, and nucleic acids. While the functional diversity and endocrine roles of adipose tissues are well-documented, a comparative analysis of the functions of EVs released by different adipose tissues from mice housed at room temperature has not been thoroughly explored. MicroRNAs (miRNAs), which are highly enriched in small extracellular vesicles (sEVs), offer a promising avenue for investigating the complex functions and unique roles of various adipose tissues. In this study, we isolated sEVs from different adipose tissues under basal conditions and performed a comprehensive analysis of their miRNA content. By comparing miRNA profiles across different adipose tissues, we aim to elucidate the potential roles of sEV-derived miRNAs in mediating intercellular communication and the distinct physiological functions of adipose tissues. Understanding the molecular features of miRNAs in adipose tissue EVs could reveal new aspects of adipose tissue biology and lay the groundwork for further research into their physiological significance.

Background: Real-world data on the use, healthcare resource utilization (HCRU), and associated costs of antifibrotic therapies in patients with idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To assess the prevalence of antifibrotic treatment, characteristics of patients receiving treatment, discontinuation rates, and HCRU and costs associated with treatment. Design: This retrospective study analyzed de-identified longitudinal and cross-sectional data, respectively, from two US claims databases: Optum’s de-identified Clinformatics ® Data Mart Database (CDM; commercial claims, Medicare Advantage) and the Veterans Health Administration (VHA) database. The study periods were October 1, 2013–March 31, 2019 and October 1, 2014–September 30, 2019, respectively. Eligible individuals were adults with ⩾1 diagnosis claim for IPF. Methods: Antifibrotic prevalence, patient demographics, treatment discontinuation rates, and HCRU and costs were determined separately for each cohort and described using summary statistics. Bivariate comparisons were analyzed using Chi-square and Student’s t -tests for categorical and continuous variables, respectively. Results: Overall, 4223 and 4459 eligible patients were identified in the CDM and VHA databases, respectively. Prevalence of antifibrotic uptake was 9.2% and 29.1% and the rate of index treatment discontinuation was 47% and 66% during follow-up in the CDM and VHA cohorts, respectively. Antifibrotic-treated patients were significantly younger ( p

ABSTRACT Background The hiatal ligament, as the anatomical landmark for the completion of total mesorectal excision (TME) for ultra‐low rectal cancer, represents a continuation of the longitudinal muscle of the rectum. It receives vascular supply from the median sacral artery and contains lymphatic vessels. In cases where ultra‐low rectal cancer is located in the posterior rectal wall, the hiatal ligament may theoretically serve as an anatomical region susceptible to direct tumor cell spread or distant metastasis. Objective To evaluate the effect of circumferential tumor location (CTL) on postoperative survival of low rectal cancer and to determine the effect of total hiatal ligament excision (THLE) on the prognosis of patients with posterior rectal cancer. Methods Patients with ultra‐low rectal cancer who underwent laparoscopic surgery between March 2014 and October 2021 were enrolled in this study. Propensity score matching (PSM) analysis was used to compare the clinicopathological characteristics and prognosis of patients in the posterior group and the non‐posterior group. Prognostic factors were identified using COX regression. PSM analysis was also used in the posterior tumor subgroup to compare the clinicopathological characteristics and prognosis of patients in the hiatal ligament traditional transection (HLTT) and THLE groups. Results After PSM, OS, and DFS were comparable between the posterior and non‐posterior groups. Similarly, no difference was noted in the local recurrence rate between the two groups (p = 0.23). The prognosis of ultra‐low rectal cancer was not affected by CTL. However, the local recurrence rate was significantly lower in the THLE group compared with the HLTT group (p = 0.023). Multivariate analysis of the posterior group identified CRM, TNM stage III, and HLTT as independent risk factors for local recurrence‐free survival. Conclusions CTL is not a prognostic risk factor for low rectal cancer. In posterior wall tumors, THLE significantly reduces the local recurrence rate for low rectal cancer.

Objective: Chronic bowel disease has the characteristics of high recurrence rate, prolonged and non-healing, and the incidence has increased year by year in recent years. Cannabidiol (CBD) has significant anti-inflammatory and antioxidant activities, but it is limited by its characteristics of fat solubility and low bioavailability. This study aims to treat chronic inflammatory bowel disease by preparing a CBD-loaded hydrogel system (GelMA + CBD) that can deliver CBD in situ and improve its bioavailability through slow release. Method: The study designed and constructed GelMA + CBD, and its surface morphology was observed by scanning electron microscopy, and its pore size, swelling rate and release rate were evaluated to evaluate its bioactivity and biosafety. The expression of various inflammatory factors was detected by ELISA, and the expression of protein and reactive oxygen species were observed by laser confocal microscopy to evaluate their anti-inflammatory and antioxidant properties. Results: Our study found that GelMA + CBD with biosafety, could make CBD be slowly released, and effectively inhibit the M1-type polarization of macrophages in vitro, and promote the M2-type polarization. In addition, GelMA + CBD can also reduce the expression of pro-inflammatory factors (such as iNOS) in macrophages, and increase the expression of anti-inflammatory factors (such as Arg-1), clear intracellular reactive oxygen species (ROS), and relieve oxidative stress. Conclusion: The vitro experiments have confirmed that the CBD-loaded hydrogel system has good biosafety, and can alleviate inflammation by regulating the polarization direction of macrophages, and then inhibiting the secretion of pro-inflammatory factors, laying a strong foundation for the treatment of chronic enteritis.

ABSTRACT: Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.

Study region: The Amur River Basin (ARB), a transboundary river basin comprising four sub-regions: the Northeast Plain of China, Mongolian Plateau, Siberian Federal region and Far East Federal region. Study focus: This research presents a comprehensive analysis on the lake dynamics in both lake area and number across the entire ARB from 1999 to 2021, using multi-source remote sensing datasets. The driving mechanisms are analyzed, considering the gradients in climatic conditions and varying levels of anthropogenic activities in different sub-regions. New hydrological insights for the region: The study found that both the total area and number of lakes in ARB decreased before 2009, whereafter increased significantly until 2021. Specifically, lakes in the Mongolian Plateau shrank seriously (-46.6 km2 yr−1), while those in the Northeast Plain of China, Siberian Federal region, and Far Eastern Federal region all showed overall expanding trends. Lake changes in the entire ARB were predominantly influenced by precipitation (R2:0.54,) and soil moisture (R2:0.55). Increasing irrigation and grazing were the main forces in the Mongolian Plateau, while hydro-climatic factors played more important roles in Northeast Plain, Siberian Federal region, and Far Eastern Federal region. This study provides a comprehensive cross-regional analysis of lake area changes and driving forces, which is of great value in ensuring lake ecological safety in ARB and other regions with densely distributed lakes.

Abstract Flexible microwave absorber (MAR), vital in advanced applications such as wearable electronics and precision devices, are highly valued for their lightweight, exceptional electromagnetic waves (EWs), and ease of fabrication. However, optimizing the electromagnetic parameters of microwave absorption materials (MAMs) to enhance absorption ability and expand effective absorption broadband (EAB, reflection loss (RL)

Abstract Herein, hierarchically structured microgrid frameworks of Co3O4 and carbon composite deposited on reduced graphene oxide (Co3O4@C/rGO) are demonstrated through the three‐dimensioinal (3D) printing method, where the porous structure is controllable and the height and width are scalable, for dendrite‐free Na metal deposition. The sodiophilicity, facile Na metal deposition kinetics, and NaF‐rich solid electrolyte interphase (SEI) formation of cubic Co3O4 phase are confirmed by combined spectroscopic and computational analyses. Moreover, the uniform and reversible Na plating/stripping process on 3D‐printed Co3O4@C/rGO host is monitored in real time using in situ transmission electron and optical microscopies. In symmetric cells, the 3D printed Co3O4@C/rGO electrode achieves a long‐term stability over 3950 at 1 mA cm−2 and 1 mAh cm−2 with a superior Coulombic efficiency (CE) of 99.87% as well as 120 h even at 20 mA cm−2 and 20 mAh cm−2, far exceeding the previously reported carbon‐based hosts for Na metal anodes. Consequently, the full cells of 3D‐printed Na@Co3O4@C/rGO anode with 3D‐printed Na3V2(PO4)3@C‐rGO cathode (≈15.7 mg cm−2) deliver the high specific capacity of 97.97 mAh g−1 after 500 cycles with a high CE of 99.89% at 0.5 C, demonstrating the real operation of flexible Na metal batteries.

Background Passion fruit (Passiflora edulis) is loved for its delicious flavor and nutritious juice. Although studies have delved into the cultivation and enhancement of passion fruit varieties, the underlying factors contributing to the fruit’s appealing aroma remain unclear. Methods This study analyzed the full-length transcriptomes of two passion fruit cultivars with different flavor profiles: “Tainong 1” (TN1), known for its superior fruit flavor, and “Guihan 1” (GH1), noted for its strong environmental resilience but lackluster taste. Utilizing PacBio Iso-Seq and Illumina RNA-Seq technologies, we discovered terpene synthase (TPS) genes implicated in fruit ripening that may help explain the flavor disparities. Results We generated 15,913 isoforms, with N50 lengths of 1,500 and 1,648 bp, and mean lengths of 1,319 and 1,463 bp for TN1 and GH1, respectively. Transcript and isoform lengths ranged from a maximum of 7,779 bp to a minimum of 200 and 209 bp. We identified 14,822 putative coding DNA sequences (CDSs) averaging 1,063 bp, classified 1,007 transcription factors (TFs) into 84 families. Additionally, differential expression analysis of ripening fruit from both cultivars revealed 314 upregulated and 43 downregulated unigenes in TN1 compared to GH1. The top 10 significantly enriched Gene Ontology (GO) terms for the differentially expressed genes (DEGs) indicated that TN1’s upregulated genes were primarily involved in nutrient transport, whereas GH1’s up-regulated genes were associated with resistance mechanisms. Meanwhile, 17 PeTPS genes were identified in P. edulis and 13 of them were TPS-b members. A comparative analysis when compared PeTPS with AtTPS highlighted an expansion of the PeTPS-b subfamily in P. edulis, suggesting a role in its fruit flavor profile. Conclusion Our findings explain that the formation of fruit flavor is attributed to the upregulation of essential genes in synthetic pathway, in particular the expansion of TPS-b subfamily involved in terpenoid synthesis. This finding will also provide a foundational genetic basis for understanding the nuanced flavor differences in this species.

The Yan’an gas field in the Ordos Basin is a typical deep coalbed methane field with tremendous resource potential. Evaluation methods for gas content in deep coal seams are urgently required to be established. This study is aimed at quantitatively analyzing the gas content of coalbed methane in deep coalbed methane reservoirs and revealing its influencing factors. With the coal rock samples of typical deep coalbed methane wells in the Yan’an gas field of the Ordos Basin as the research objects, the gas-bearing characteristics of deep coal rocks were analyzed, and the main controlling factors of gas-bearing properties were explored. The research results indicate that (1) the deep coal seams in the Yan’an gas field have a considerable thickness, a high total organic carbon content, and the potential of pyrolysis hydrocarbon generation is generally elevated, presenting excellent hydrocarbon generation potential. (2) Various types of pores and fractures in the deep coal rocks of the Yan’an gas field are well-developed, providing a favorable preservation space and migration channel for deep coalbed methane. (3) The total gas content of on-site analysis of deep coalbed methane in the Yan’an gas field is relatively high, mainly existing in the form of free gas, and has significant exploration and development potential. (4) The gas content of deep coal rocks in the Yan’an gas field is jointly controlled by multiple factors such as the total organic carbon content, minerals, and pore structure. In conclusion, the deep coal seams in the Yan’an gas field have favorable reservoir-forming conditions and great exploration and development potential.

Radiotherapy is a crucial treatment for head and neck malignancies, but it can sometimes cause sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensory neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of heterozygous 8-week-old Cx3cr1GFP/+ male mice were irradiated with 30Gy of X-rays and biological samples were collected on days 1, 7, and 10 after irradiation. Auditory brainstem responses were used to assess auditory function in the mice. Changes in basilar membrane hair cells, spiral ganglion neurons (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cochlear tissue. The results showed no significant hair cell loss after a single high dose of radiation. However, the mice developed pantonal hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence showed decreased neurofilament expression. The number of macrophages in the inner ear reduced over time. RT-qPCR showed that cochlear inflammatory factors and chemokines were briefly upregulated on day 1st after irradiation and then decreased over time. In conclusion, high-dose irradiation causes acute SNHL that is not associated with hair cell loss and may be related to SGN changes. Radiation-induced SNHL is associated with a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two remains to be investigated.

Background: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. Methods: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. Results: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+ T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. Conclusion: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.

Abstract Photocatalytic coupling of methane to ethane and ethylene (C2 compounds) offers a promising approach to utilizing the abundant methane resource. However, the state-of-the-art photocatalysts usually suffer from very limited C2 formation rates. Here, we report our discovery that the anatase TiO2 nanocrystals mainly exposing {101} facets, which are generally considered less active in photocatalysis, demonstrate surprisingly better performances than those exposing the high-energy {001} facet. The palladium co-catalyst plays a pivotal role and the Pd2+ site on co-catalyst accounts for the selective C2 formation. We unveil that the anatase {101} facet favors the formation of hydroxyl radicals in aqueous phase near the surface, where they activate methane molecules into methyl radicals, and the Pd2+ site participates in facilitating the adsorption and coupling of methyl radicals. This work provides a strategy to design efficient nanocatalysts for selective photocatalytic methane coupling by reaction-space separation to optimize heterogeneous-homogeneous reactions at solid-liquid interfaces.

Abstract. Background:. Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD. Methods:. Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared. Results:. Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%–3.10%), 2.09% (95% CI: 1.76%–2.43%), and 1.25% (95% CI: 0.99%–1.51%), respectively. In multivariable models, age ≥60 years (60–69 years, odds ratio [OR]: 1.90, 95% CI: 1.11–3.25; ≥80 years, OR: 2.00, 95% CI: 1.06–3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96–13.21), urban residence (OR: 1.69, 95% CI: 1.07–2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21–2.58; senior high school or above, OR: 2.61, 95% CI: 1.69–4.03), former smoking (OR: 1.79, 95% CI: 1.15–2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29–4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45–0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment. Conclusions:. Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Abstract Background Plant cell walls have evolved precise plasticity in response to environmental stimuli. The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits. However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown. Results In this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification. The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls. The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mechanical properties relative to the wild-type, leading to a substantial improvement in lodging resistance. Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI). Additionally, the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition. Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymatic saccharification of biomass after the alkali pretreatment. Furthermore, the comparative transcriptome analysis revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis. Conclusions Our findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

Abstract Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists’ experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l’Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.