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Abstract Background Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. Methods In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. Results There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract Background Drug repositioning has the potential to reduce costs and accelerate the rate of drug development, with highly promising applications. Currently, the development of artificial intelligence has provided the field with fast and efficient computing power. Nevertheless, the repositioning of traditional Chinese medicine (TCM) is still in its infancy, and the establishment of a reasonable and effective research method is a pressing issue that requires urgent attention. The use of graph neural network (GNN) to compute the similarity between TCM prescriptions to develop a method for finding their new indications is an innovative attempt. Methods This paper focused on traditional Chinese medicine prescriptions containing ephedra, with 20 prescriptions for treating external cough and asthma taken as target prescriptions. The remaining 67 prescriptions containing ephedra were taken as to-be-matched prescriptions. Furthermore, a multitude of data pertaining to the prescriptions, including diseases, disease targets, symptoms, and various types of information on herbs, was gathered from a diverse array of literature sources, such as Chinese medicine databases. Then, cosine similarity and Jaccard coefficient were calculated to characterize the similarity between prescriptions using graph convolutional network (GCN) with a self-supervised learning method, such as deep graph infomax (DGI). Results A total of 1340 values were obtained for each of the two calculation indicators. A total of 68 prescription pairs were identified after screening with 0.77 as the threshold for cosine similarity. Following the removal of false positive results, 12 prescription pairs were deemed to have further research value. A total of 5 prescription pairs were screened using a threshold of 0.50 for the Jaccard coefficient. However, the specific results did not exhibit significant value for further use, which may be attributed to the excessive variety of information in the dataset. Conclusions The proposed method can provide reference for finding new indications of target prescriptions by quantifying the similarity between prescriptions. It is expected to offer new insights for developing a scientific and systematic research methodology for traditional Chinese medicine repositioning.

Abstract Lithium is key for a clean energy transition but faces sustainability challenges in the global supply. Here, we use a bottom-up approach to study the evolution of the global lithium-ion battery industry from 2023 to 2050. The supply and demand trends are predicted to determine the supply potential and allocation structure of primary and secondary lithium. The results indicate a projected global lithium demand of 1.93 million metric tons in 2050, a significant increase of 26.2 times compared to 2023. In the process of global lithium resources shifting from underground reserves to in-use stocks, population and Gross Domestic Product (GDP) influence regions’ lithium endowment and per capita primary consumption, respectively. If the European Union’s new battery regulation is implemented globally, then it is projected to reduce global primary lithium consumption by 1.03 million metric tons by 2050, with a 53.48% decrease in the proportion of primary lithium consumption.

In order to investigate the mechanical response behavior of the gas obturator of the breech mechanism, made of polychloroprene rubber (PCR), uniaxial compression experiments were carried out by using a universal testing machine and a split Hopkinson pressure bar (SHPB), obtaining stress-strain responses at different temperatures and strain rates. The results revealed that, in comparison to other polymers, the gas obturator material exhibited inconspicuous strain softening and hardening effects; meanwhile, the mechanical response was more affected by the strain rate than by temperature. Subsequently, a succinct viscoelastic damage constitutive model was developed based on the ZWT model, including ten undetermined parameters, formulated with incorporating three parallel components to capture the viscoelastic response at high strain rate and further enhanced by integrating a three-parameter Weibull function to describe the damage. Compared to the ZWT model, the modified model could effectively describe the mechanical response behavior of the gas obturator material at high strain rates. This research laid a theoretical foundation for further investigation into the influence of chamber sealing issues on artillery firing.

Abstract Bladder cancer (BCa) stands out as a highly prevalent malignant tumor affecting the urinary system. The Sex determining region Y-box protein family is recognized for its crucial role in BCa progression. However, the effect of Sex determining region Y-box 7 (SOX7) on BCa progression has not been fully elucidated. Herein, RNA-sequencing, western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF) and tissue microarray were utilized to assess SOX7 expression in vitro and in vivo. Additionally, SOX7 expression, prognosis, and SOX7 + cytoglobin (CYGB) score were analyzed using R software. In vitro and vivo experiments were performed with BCa cell lines to validate the effect of SOX7 knockdown and overexpression on the malignant progression of BCa. The results showed that SOX7 exhibits low expression in BCa. It functions in diverse capacities, inhibiting the proliferative, migratory, and invasive capabilities of BCa. In addition, the experimental database demonstrated that SOX7 binds to the promoter of DNA methyltransferase 3 beta (DNMT3B), leading to the transcriptional inhibition of DNMT3B. This subsequently results in a reduced methylation of CYGB promoter, ultimately inhibiting the tumor progression of BCa. SOX7 + CYGB scores were significantly linked to patient prognosis. In conclusion, SOX7 inhibits the malignant progression of BCa via the DNMT3B/CYGB axis. Additionally, the SOX7 + CYGB score is capable of predicting the prognostic outcomes of BCa patients. Therefore, SOX7 and CYGB may play an important role in the progression of bladder cancer, and they can be used as prognostic markers of bladder cancer patients.

Abstract To address the problems of low accuracy in fault diagnosis of oil-immersed transformers, poor state perception ability and real-time collaboration during diagnosis feedback, a fault diagnosis method for transformers based on the integration of digital twins is proposed. Firstly, fault sample balance is achieved through Iterative Nearest Neighbor Oversampling (INNOS), Secondly, nine-dimensional ratio features are extracted, and the correlation between dissolved gases in oil and fault types is established. Then, sparse principal component analysis (SPCA) is used for feature fusion and dimensionality reduction. Finally, the Aquila Optimizer (AO) is introduced to optimize the parameters of the Kernel Extreme Learning Machine (KELM), establishing the optimal AO-KELM diagnosis model. The final fault diagnosis accuracy reaches 98.1013%. Combining transformer digital twin models, real-time interaction mapping between physical entities and virtual space is achieved, enabling online diagnosis of transformer faults. Experimental results show that the method proposed in this paper has high diagnostic accuracy and strong stability, providing reference for the intelligent operation and maintenance of transformers.

Background: Immunotherapy has emerged as a novel strategy for cancer treatment following surgery, radiotherapy, and chemotherapy. Immune checkpoint blockade and Chimeric antigen receptor (CAR)-T cell therapies have been successful in clinical trials. Cancer cells evade immune surveillance by hijacking inhibitory pathways via overexpression of checkpoint genes. The Cluster of Differentiation 47 (CD47) has emerged as a crucial checkpoint for cancer immunotherapy by working as a “don’t eat me” signal and suppressing innate immune signaling. Furthermore, CD47 is highly expressed in many cancer types to protect cancer cells from phagocytosis via binding to SIRPα on phagocytes. Targeting CD47 by either interrupting the CD47-SIRPα axis or combing with other therapies has been demonstrated as an encouraging therapeutic strategy in cancer immunotherapy. Antibodies and small molecules that target CD47 have been explored in pre- and clinical trials. However, formidable challenges such as the anemia and palate aggregation cannot be avoided because of the wide presentation of CD47 on erythrocytes. Aim of view: This review summarizes the current knowledge on the regulation and function of CD47, and provides a new perspective for immunotherapy targeting CD47. It also highlights the clinical progress of targeting CD47 and discusses challenges and potential strategies. Key scientific concepts of review: This review provides a comprehensive understanding of targeting CD47 in cancer immunotherapy, it also augments the concept of combination immunotherapy strategies by employing both innate and adaptive immune responses.

Oxide-dispersion-strengthened (ODS) steels are candidate materials for application in advanced nuclear reactors. In this study, the low-cycle fatigue performances of 13Cr-ODS ferritic steel pipes were investigated at 600, 700, and 800 °C. Cyclic softening was observed at high strain amplitudes with an increase in the number of fatigue cycles. However, cyclic hardening appeared first, and then cyclic softening occurred at a low strain amplitude with the increase in the number of fatigue cycles. By comparing the cyclic stress–strain curves and the monotonic stress–strain curves, it was found that cyclic softening occurred regardless of the strain amplitude. The Coffin–Manson and Basquin equations were used to predict the fatigue of the pipes. Microstructure analysis indicated that cyclic softening was induced by the dynamic recovery and recrystallization, which reduced the number of low-angle grain boundaries in the deformed grains by promoting dislocation annihilation and reorganization. A complex multi-layer core–shell structure with a large size (∼500 nm) was observed.

Background: Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair. Method: In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and in vitro biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the in vivo biological effect of the scaffold after implantation. Results: The in vitro and in vivo results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering. Conclusion: The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances in vitro and in vivo, which properties are well-suited with the requirement for treating diabetic bone defects. Translational potential of this article: The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.

Objectives: The objective of this study was to investigate the resistance mechanisms of a multidrug-resistant Salmonella Kentucky ST198 FJ-2064 isolated from a patient in China. Methods: The antimicrobial susceptibility of FJ-2064 was determined by the standard disc dilution and broth microdilution methods. The complete genome of FJ-2064 was sequenced using PacBio and Illumina MiSeq platforms. Polymerase chain reaction (PCR) and S1-PFGE were utilized to confirm the mutation sites and the genomic plasmids, respectively. Results: Isolate FJ-2064 belongs to sequence type ST198 and harboured no visible large plasmids, but was concurrent resistant to 22 detected antimicrobial agents including cefotaxime, ciprofloxacin, and azithromycin. The complete genome sequence identified 20 acquired antibiotic resistance genes (ARGs) and five chromosomal mutations in the gyrA and parC genes of the quinolone resistance determining regions (QRDRs) in FJ-2064. In addition, PCR sequencing confirmed that most of the ARGs were clustered on one multidrug-resistant region and a variant of SGI1-K. In particular, the bla-TEM-1 and bla-CTX−M-55, qnrS1, mph(A) genes, which confer resistance to cephalosporins, quinolones, and macrolides respectively, were all located on the multidrug-resistant region. Conclusions: We have demonstrated one multidrug-resistant region and a variant of SGI1-K in a Salmonella Kentucky ST198 that is co-resistant to cefotaxime, ciprofloxacin, and azithromycin.

Due to matching biomechanical properties and significant biological activity, Mg-based implants present great potential in orthopedic applications. In recent years, the biocompatibility and therapeutic effect of magnesium-based implants have been widely investigated in trauma repair. In contrast, the R&D work of Mg-based implants in spinal fusion is still limited. This review firstly introduced the general background for Mg-based implants. Secondly, the mechanical properties and degradation behaviors of Mg and its traditional and novel alloys were reviewed. Then, different surface modification techniques of Mg-based implants were described. Thirdly, this review comprehensively summarized the biological pathways of Mg degradation to promote bone formation in neuro-musculoskeletal circuit, angiogenesis with H-type vessel formation, osteogenesis with osteoblasts activation and chondrocyte ossification as an integrated system. Fourthly, this review followed the translation process of Mg-based implants via updating the preclinical studies in fracture fixation, sports trauma repair and reconstruction, and bone distraction for large bone defect. Furthermore, the pilot clinical studies were involved to demonstrate the reliable clinical safety and satisfactory bioactive effects of Mg-based implants in bone formation. Finally, this review introduced the background of spine fusion surgeryand the challenges of biological matching cage development. At last, this review prospected the translation potential of a hybrid Mg-PEEK spine fusion cage design.

Oxy-combustion is a promising carbon-capture technology, but atmospheric-pressure oxy-combustion has a relatively low net efficiency, limiting its application in power plants. In pressurized oxy-combustion (POC), the boiler, air separation unit, flue gas recirculation unit, and CO2 purification and compression unit are all operated at elevated pressure; this makes the process more efficient, with many advantages over atmospheric pressure, such as low NOx emissions, a smaller boiler size, and more. POC is also more promising for industrial application and has attracted widespread research interest in recent years. It can produce high-pressure CO2 with a purity of approximately 95%, which can be used directly for enhanced oil recovery or geo-sequestration. However, the pollutant emissions must meet the standards for carbon capture, storage, and utilization. Because of the high oxygen and moisture concentrations in POC, the formation of acids via the oxidation and solution of SOx and NOx can be increased, causing the corrosion of pipelines and equipment. Furthermore, particulate matter (PM) and mercury emissions can harm the environment and human health. The main distinction between pressurized and atmospheric-pressure oxy-combustion is the former’s elevated pressure; thus, the effect of this pressure on the pollutants emitted from POC—including SOx, NOx, PM, and mercury—must be understood, and effective control methodologies must be incorporated to control the formation of these pollutants. This paper reviews recent advances in research on SOx, NOx, PM, and mercury formation and control in POC systems that can aid in pollutant control in such systems.

In response to thermal runaway (TR) of electric vehicles, recent attention has been focused on mitigation strategies such as efficient heat dredging in battery thermal management. Thermal management with particular focus on battery cooling has been becoming increasingly significant. TR usually happened when an electric vehicle is unpowered and charged. In this state, traditional active battery cooling schemes are disabled, which can easily lead to dangerous incidents due to loss of cooling ability, and advanced passive cooling strategies are therefore gaining importance. Herein, we developed an enhanced thermal radiation material, consisting of ∼1 ​μm thick multilayered nano-sheet graphene film coated upon the heat dissipation surface, thereby enhancing thermal radiation in the nanoscale. The surface was characterized on the nanoscale, and tested in a battery-cooling scenario. We found that the graphene-based coating's spectral emissivity is between 91 ​% and 95 ​% in the mid-infrared region, and thermal experiments consequently illustrated that graphene-based radiative cooling yielded up to 15.1 ​% temperature reduction when compared to the uncoated analogue. Using the novel graphene surface to augment a heat pipe, the temperature reduction can be further enlarged to 25.6 ​%. The new material may contribute to transportation safety, global warming mitigation and carbon neutralization.

Abstract Background Facing the significant challenge of overcoming drug resistance in cancer treatment, particularly resistance caused by mutations in epidermal growth factor receptor (EGFR), the aim of our study was to identify potent EGFR inhibitors effective against the T790M/C797S/L858R mutant, a key player in resistance mechanisms. Methods Our integrated in silico approach harnessed machine learning, virtual screening, and activity evaluation techniques to screen 5105 compounds from three libraries, aiming to find candidates capable of overcoming the resistance conferred by the T790M and C797S mutations within EGFR. This methodical process narrowed the search down to six promising compounds for further examination. Results Kinase assays identified three compounds to which the T790M/C797S/L858R mutant exhibited increased sensitivity compared to the T790M/L858R mutant, highlighting the potential efficacy of these compounds against resistance mechanisms. Among them, T001-10027877 exhibited dual inhibitory effects, with IC50 values of 4.34 µM against EGFRT790M/C797S/L858R and 1.27 µM against EGFRT790M/L858R. Further investigations into the antiproliferative effects in H1975, A549, H460 and Ba/F3-EGFRL858/T790M/C797S cancer cells revealed that T001-10027877 was the most potent anticancer agent among the tested compounds. Additionally, the induction of H1975 cell apoptosis and cell cycle arrest by T001-10027877 were confirmed, elucidating its mechanism of action. Conclusions This study highlights the efficacy of combining computational techniques with bioactivity assessments in the quest for novel antiproliferative agents targeting complex EGFR mutations. In particular, T001-10027877 has great potential for overcoming EGFR-mediated resistance and merits further in vivo exploration. Our findings contribute valuable insights into the development of next-generation anticancer therapies, demonstrating the power of an integrated drug discovery approach.

Abstract Although the relationship between hypertension and hyperuricemia is widely recognized, there is still a relative lack of research on prehypertensive individuals and the individual associations of systolic and diastolic blood pressure with the risk of hyperuricemia. From 2011 to 2016, we conducted a study on 53,323 individuals at Wuhu City Hospital in China. Based on initial blood pressure readings, participants were categorized into normal, prehypertension, or hypertension groups. We used Cox regression to analyze the associations with baseline factors. In subgroup analyses, systolic and diastolic pressures were treated as continuous variables, and their relationship with the risk of hyperuricemia was examined using restricted cubic spline analysis. The risk increased in the prehypertension and hypertension groups compared to the normal blood pressure group, with hazard ratios of 1.192 and 1.350, respectively. For each unit increase in blood pressure, the risk of hyperuricemia rose by 0.8% (systolic) and 0.9% (diastolic), especially when blood pressure levels exceeded 115/78 mmHg. Additionally, we observed that factors such as gender, alcohol consumption habits, obesity, and dyslipidemia might further influence this association. These findings emphasize the importance of early risk assessment and intervention in these patient populations in clinical practice.

Abstract Background Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF. Methods The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants. Results During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (P interaction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02–1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF. Conclusions Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Abstract Day-Night imaging technology that obtains full-color and infrared images has great market demands for security monitoring and autonomous driving. The current mainstream solution relies on wide-spectrum silicon photodetectors combined with Infrared Cutfilter Removal, which increases complexity and failure rate. Here, we address these challenges by employing a perovskite photodetector based on Pb−Sn alloyed single crystal with a vertical bandgap-graded structure that presents variable-spectrum responses at different biases and extends the infrared detection range close to 1100 nm. Taking advantage of the Pb−Sn gradients in mobility and built-in field, the perovskite photodetector shows a large linear dynamic range of 177 dB. In addition, the optoelectronic characteristics feature long-term operational stability over a year. We further develop an imaging module prototype without Infrared Cutfilter Removal that exhibits excellent color fidelity with RGB color differences ranging from 0.48 to 2.46 under infrared interference and provides over 26-bit grayscale resolution in infrared imaging.

Abstract Background Glioblastoma (GBM) is a malignant astrocytic tumor and its progression involves the regulation of vascular endothelial growth factor-A (VEGFA). However, the mechanism of VEGFA in regulating GBM progression remains unclear. Methods VEGFA mRNA expression was analyzed by quantitative real-time polymerase chain reaction. Protein expression of VEGFA, cluster of differentiation 9 (CD9), CD81, and transforming growth factor-β1 (TGF-β1) was detected by western blotting assay. Flow cytometry assay was conducted to assess cell proliferation, cell apoptosis and myeloid-derived suppressor cell (MDSC) differentiation. TUNEL cell apoptosis detection kit was utilized to analyze cell apoptosis of tumors. Angiogenic capacity was investigated by tube formation assay. Transwell assay was used to assess cell migration and invasion. The effect of VEGFA on tumor formation was determined by a xenograft mouse model assay. Immunohistochemistry assay was used to analyze positive expression rate of VEGFA in tumor tissues. TGF-β1 level was detected by enzyme-linked immunosorbent assay. Results VEGFA expression was upregulated in GBM tissues, GBM cells, and exosomes from GBM patients and GBM cells. VEGFA silencing led to decreased cell proliferation, tube formation, migration and invasion and increased cell apoptosis. Moreover, VEGFA knockdown also delayed tumor formation. VEGFA promoted MDSC differentiation and TGF-β1 secretion by MDSCs by being packaged into exosomes. In addition, TGF-β1 knockdown displayed similar effects with VEGFA silencing on GBM cell phenotypes, and MDSCs attenuated VEGFA knockdown-induced effects by secreting TGF-β1 in A172 and U251 cells. Conclusion VEGFA contributed to tumor property of GBM cells by promoting MDSC differentiation and TGF-β1 secretion by MDSCs, providing potential targets for GBM treatment.

Abstract Straw pollution and the increasing scarcity of phosphorus resources in many regions of China have had severe impacts on the growing conditions for crop plants. Using microbial methods to enhance straw decomposition rate and phosphorus utilization offers effective solutions to address these problems. In this study, a microbial consortium 6 + 1 (consisting of a straw-degrading bacterium and a phosphate-solubilizing bacterium) was formulated based on their performance in straw degradation and phosphorus solubilization. The degradation rate of straw by 6 + 1 microbial consortium reached 48.3% within 7 days (The degradation ability was 7% higher than that of single bacteria), and the phosphorus dissolution rate of insoluble phosphorus reached 117.54 mg·L− 1 (The phosphorus solubilization ability was 29.81% higher than that of single bacteria). In addition, the activity of lignocellulosic degrading enzyme system was significantly increased, the activities of endoglucanase, β-glucosidase and xylanase in the microbial consortium were significantly higher than those in the single strain (23.16%, 28.02% and 28.86%, respectively). Then the microbial consortium was processed into microbial agents and tested in rice pots. The results showed that the microbial agent significantly increased the content of organic matter, available phosphorus and available nitrogen in the soil. Ongoing research focuses on the determination of the effects and mechanisms of a functional hybrid system of straw degradation and phosphorus removal. The characteristics of the two strains are as follows: Straw-degrading bacteria can efficiently degrade straw to produce glucose-based carbon sources when only straw is used as a carbon source. Phosphate-solubilizing bacteria can efficiently use glucose as a carbon source, produce organic acids to dissolve insoluble phosphorus and consume glucose at an extremely fast rate. The analysis suggests that the microbial consortium 6 + 1 outperformed individual strains in terms of both performance and application effects. The two strains within the microbial consortium promote each other during their growth processes, resulting in a significantly higher rate of carbon source consumption compared to the individual strains in isolation. This increased demand for carbon sources within the growth system facilitates the degradation of straw by the strains. At the same time, the substantial carbon consumption during the metabolic process generated a large number of organic acids, leading to the solubilization of insoluble phosphorus. It also provides a basis for the construction of this type of microbial consortium.

Abstract Multi‐agent reinforcement learning relies on reward signals to guide the policy networks of individual agents. However, in high‐dimensional continuous spaces, the non‐stationary environment can provide outdated experiences that hinder convergence, resulting in ineffective training performance for multi‐agent systems. To tackle this issue, a novel reinforcement learning scheme, Mutual Information Oriented Deep Skill Chaining (MioDSC), is proposed that generates an optimised cooperative policy by incorporating intrinsic rewards based on mutual information to improve exploration efficiency. These rewards encourage agents to diversify their learning process by engaging in actions that increase the mutual information between their actions and the environment state. In addition, MioDSC can generate cooperative policies using the options framework, allowing agents to learn and reuse complex action sequences and accelerating the convergence speed of multi‐agent learning. MioDSC was evaluated in the multi‐agent particle environment and the StarCraft multi‐agent challenge at varying difficulty levels. The experimental results demonstrate that MioDSC outperforms state‐of‐the‐art methods and is robust across various multi‐agent system tasks with high stability.

Landslides induced by reservoir inundation are common in Southwest China, negatively influencing hydropower stations. The Wunonglong hydropower station dam was constructed in the upper reaches of the Lancang River, accordingly causing the water level at the Lajinshengu slope to increase by 30 m. A tension crack with a visible depth of 8 m was observed in the upper sector of the Lajinshengu slope after reservoir impoundment for 170 d. In the following days, numerous cracks appeared on the surface of the slope, and the maximum displacement of the slope reached 3.22 m. Then, a large-scale active deformation body within the Lajinshengu slope formed with an area of 2.62 × 105 m2 and a volume of 1.65 × 107 m3. Detailed field investigations, on-site monitoring, and centrifugal model tests were carried out to analyze the surface features, deformation characteristics, and failure mechanism of the Lajinshengu slope. The results show that the slope is an ancient landslide, divided into two parts (i.e. zone A and zone B) by the gully. Zone B is a traction landslide caused by the displacement of zone A. The long-term inundation weakens the soft rock at the slope foot, intensifying the toppling of bedrock and consequently triggering the sliding of the overburden in zone A. The failure mode of the Lajinshengu slope is a typical case of toppling-sliding failure, and the underlying rock toppling drives the overlying sliding. In addition, early identification methods for toppling deformation covered by overburdened soil were proposed based on monitoring data and deformation signs.

Abstract Video Anomaly Detection (VAD) has been an active research field for several decades. However, most existing approaches merely extract a single type of feature from videos and define a single paradigm to indicate the extent of abnormalities. A coarse‐to‐fine three‐level prediction is built by integrating different levels of spatio‐temporal representations, better highlighting the difference between normal and abnormal behaviors. First, an object‐level trajectory prediction is proposed to model human historical position using a graph transformer network. Subsequently, skeleton‐level prediction is achieved by incorporating the positional information from the trajectory prediction. More importantly, based on the predicted skeleton, a skeleton‐guided pixel‐level region prediction is performed. A novel Skeleton Conditioned Generative Adversarial Network (SCGAN) is designed to explore the correlation between skeleton‐level and pixel‐level motion prediction. Benefiting from SCGAN, the prediction of human regions is contributed by both coarse‐grained and fine‐grained motion features. This three‐level prediction, namely Progressive Prediction Video Anomaly Detection (P3VAD), enlarges the prediction error on irregular motion patterns. Besides, a pixel‐level analysis method is proposed to achieve Background‐bias Elimination (BE) and denoise the predicted region. Experimental results validate the effectiveness of P3VAD on the four benchmark datasets (ShanghaiTech, CUHK Avenue, IITB‐Corridor, and ADOC).

Abstract Background Hepatocellular carcinoma (HCC) poses a serious threat to human health worldwide. lncRNA dysregulation is frequently observed in various cancers, including HCC. However, the function of LINC01370 in HCC progression and its underlying mechanisms remain unclear. Methods LINC01370 expression in HCC tissues with cells was analyzed by applying the GEO and GEPIA databases and qRT-PCR. CCK-8 and Transwell assays were used to assess HCC cell proliferation, migration, and invasion. The PI3K, AKT, with p-AKT protein expression were analyzed by western blotting. Results Gene Expression Omnibus (GEO) and Gene Expression Profiling Interactive Analysis (GEPIA) showed that LINC01370 expression was significantly lower in HCC tissues than in normal tissues. LINC01370 overexpression markedly repressed HepG2 SMMC-7721 cells proliferation, migration, and invasion. To understand the downstream mechanism of LINC01370 regulation, we further analyzed the genes co-expressed with LINC01370 in GSE136247 and GSE132037 and then performed KEGG analysis. The PA pathway was found to be a downstream pathway regulated by LINC01370 in GSE136247 and GSE132037 via gene co-expression and KEGG analysis. Furthermore, PI3K and p-AKT protein levels decreased after LINC01370 overexpression. Importantly, rescue experiments showed that activation of the PI3K/AKT pathway disrupted the repressive effect of LINC01370 overexpression on the proliferation, migration, and invasion of HepG2 of SMMC-7721 cells. Conclusions This study verified that LINC01370 suppresses HCC proliferation with metastasis by regulating the PI3K/AKT pathway.

Abstract Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Pheretimoid earthworms, Amynthas carnosus, were collected from Northeast and North China. An update on the distribution and systematics of the A. carnosus complex in eastern Asia using both morphological and molecular data is provided. Three subspecies, A. carnosus carnosus, A. carnosus naribunji, and A. carnosus roki, are confirmed. Comparisons of morphological characters between the subspecies of A. carnosus are provided. Our results support the subspecies assignment with an intraspecific K2P genetic distance of not greater than 10% using the mitochondrial cytochrome c oxidase subunit I (COI). In addition, a re-description of the morphology of A. carnosus naribunji is presented here.

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract Background Most Chinese joint entity and relation extraction tasks in medicine involve numerous nested entities, overlapping relations, and other challenging extraction issues. In response to these problems, some traditional methods decompose the joint extraction task into multiple steps or multiple modules, resulting in local dependency in the meantime. Methods To alleviate this issue, we propose a joint extraction model of Chinese medical entities and relations based on RoBERTa and single-module global pointer, namely RSGP, which formulates joint extraction as a global pointer linking problem. Considering the uniqueness of Chinese language structure, we introduce the RoBERTa-wwm pre-trained language model at the encoding layer to obtain a better embedding representation. Then, we represent the input sentence as a third-order tensor and score each position in the tensor to prepare for the subsequent process of decoding the triples. In the end, we design a novel single-module global pointer decoding approach to alleviate the generation of redundant information. Specifically, we analyze the decoding process of single character entities individually, improving the time and space performance of RSGP to some extent. Results In order to verify the effectiveness of our model in extracting Chinese medical entities and relations, we carry out the experiments on the public dataset, CMeIE. Experimental results show that RSGP performs significantly better on the joint extraction of Chinese medical entities and relations, and achieves state-of-the-art results compared with baseline models. Conclusion The proposed RSGP can effectively extract entities and relations from Chinese medical texts and help to realize the structure of Chinese medical texts, so as to provide high-quality data support for the construction of Chinese medical knowledge graphs.

Abstract Background Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. Methods To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. Results The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. Conclusions Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.

Abstract The development of cathode materials with controllable physicochemical structures and explicit catalytic sites is important in rechargeable Zn–air batteries (ZABs). Covalent organic frameworks (COFs) have garnered increasing attention owing to their facile synthesis methods, ordered pore structure, and selectivity of functional groups. However, the sluggish kinetics of oxygen evolution reaction (OER) or oxygen reduction reaction (ORR) inhibit their practical applications in ZABs. Herein, nucleophilic substitution is adopted to synthesize pyridine bi‐triazine covalent organic framework (denoted as O‐COF), and meanwhile, ionothermal conversion synthesis is employed to load MOx (M=Fe, Co) onto carbon nanosheet (named as FeCo@NC) to modulate the electronic structure. The Fe, Co‐N codoped carbon material possesses a large portion of pyridinic N and M‐N, high graphitization, and a larger BET surface area. An outstanding bifunctional activity has been exhibited in FeCo@NC, which provides a small voltage at 10 mA cm−2 for OER (E10 = 1.67 V) and a remarkable half‐wave voltage for ORR (E1/2 = 0.86 V). More impressively, when assembling ZABs, it displays notable rate performance, significant specific capacity (783.9 mAh gZn−1), and satisfactory long‐term endurance. This method of regulating covalent organic framework and ionothermal synthesis can be extended to design diverse catalysts.

Abstract Background The role of miR-145-5p in non-small cell lung cancer (NSCLC) has been studied, however, the regulation of hBMSCs-derived exosomes (Exo) transmitted miR-145-5p in NSCLC was still unknown. This study aimed to investigate the role of hBMSCs-derived exosomes (Exo) in the progression of NSCLC. Methods The Exo was extracted from hBMSCs and added to A549 and H1299 cell culture, followed by the detection of cell proliferation, migration, and invasion. The correlation between the expression of miR-145-5p and SOX9, as well as their binding relationship was determined by correlation analysis, luciferase gene reporter assay and RNA pull-down assays. The in vivo animal model was established to further verify the impact of hBMSCs-Exo. Results It showed that miR-145-5p was downregulated and SOX9 was upregulated in NSCLC tissues. HBMSCs-derived Exo, and hBMSCs-Exo with overexpression of miR-145-5p could inhibit cell proliferation, migration, and invasion of both A549 and H1299 cells, and prevent against tumor progression in vivo. MiR-145-5p and SOX9 were found to be able to bind to each other, and a negative correlation were observed between the expression of them in NSCLC tissues. Furthermore, inhibition of SOX9 could reversed the suppressed role of miR-145-5p in vitro and in vivo. Conclusion Therefore, HBMSCs-Exo effectively transmitted miR-145-5p, leading to the suppression of malignant development in NSCLC through the regulation of SOX9.

Abstract Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Abstract Tin dioxide is regarded as an alternative anode material rather than graphite due to its high theoretical specific capacity. Modification with carbon is a typical strategy to mitigate the volume expansion effect of SnO2 during the charge process. Strengthening the interface bonding is crucial for improving the electrochemical performance of SnO2/C composites. Here, SnO2-embedded reduced graphene oxide (rGO) composite with a low graphene content of approximately 5 wt.% was in situ synthesized via a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. The structural integrity of the SnO2/rGO composite is significantly improved by optimizing the Sn–O–C electronic structure with CTAB, resulting a reversible capacity of 598 mAh g−1 after 200 cycles at a current density of 1 A g−1. CTAB-assisted synthesis enhances the rate performance and cyclic stability of tin dioxide/graphene composites, and boosts their application as the anode materials for the next-generation lithium-ion batteries.

Abstract This commentary explores the intersection of Global Health Diplomacy (GHD) and humanitarian action within Fragility, Conflict, and Violence (FCV) contexts. It aims at addressing the multifaceted challenges faced by communities living in these environments, where a convergence of multiple factors, including over 110 active armed conflicts, creates complex emergencies impact on large populations globally. This commentary holds three primary significances: 1) it scrutinizes the profound and enduring health consequences of major humanitarian crises on last-mile populations, highlighting the pivotal role of health diplomacy for better navigating humanitarian challenges; 2) it advocates for a paradigm shift in humanitarian approaches, recognizing GHD’s potential in shaping international cooperation, building consensus on inclusive global health policies, and enabling more effective interventions; 3) it underscores the operational impact of health diplomacy, both at diplomatic tables and on the frontlines of humanitarian efforts. Through real-world cases such as the cholera outbreak in Yemen and the response to Ebola outbreaks in DRC, the paper illustrates how diplomatic dialogue can impact health outcomes in fragile settings.

Abstract Per- and polyfluoroalkyl substances (PFAS) are persistent and bioaccumulative pollutants that can easily accumulate in soil, posing a threat to environment and human health. Current PFAS degradation processes often suffer from low efficiency, high energy and water consumption, or lack of generality. Here, we develop a rapid electrothermal mineralization (REM) process to remediate PFAS-contaminated soil. With environmentally compatible biochar as the conductive additive, the soil temperature increases to >1000 °C within seconds by current pulse input, converting PFAS to calcium fluoride with inherent calcium compounds in soil. This process is applicable for remediating various PFAS contaminants in soil, with high removal efficiencies ( >99%) and mineralization ratios ( >90%). While retaining soil particle size, composition, water infiltration rate, and cation exchange capacity, REM facilitates an increase of exchangeable nutrient supply and arthropod survival in soil, rendering it superior to the time-consuming calcination approach that severely degrades soil properties. REM is scaled up to remediate soil at two kilograms per batch and promising for large-scale, on-site soil remediation. Life-cycle assessment and techno-economic analysis demonstrate REM as an environmentally friendly and economic process, with a significant reduction of energy consumption, greenhouse gas emission, water consumption, and operation cost, when compared to existing soil remediation practices.

Ultra-low-wear polyethylene (ULWPE) is a promising material for artificial joint implants, owing to its good biocompatibility and wear resistance. However, its molecular weight is almost an order of magnitude lower than that of Ultrahigh molecular weight polyethylene (UHMWPE). The mechanism between wear resistance and the structure of ULWPE is still unknown. This study analyzed their attributes from microstructure to macroscopic performance and revealed the wear resistance mechanisms of ULWPE by conducting an in-depth investigation of four types of polyethylene, including ULWPE, UHMWPE, and high-density polyethylene. Impact tests showed that ULWPE, with a molecular weight of 282 kg/mol, exhibited an impact energy of 110 kJ/m2, surpassing the 97 kJ/m2 recorded for UHMWPE (molecular weight over 5000 kg/mol). Furthermore, tribology tests indicated that the wear rate of the most anti-wear ULWPE was 4.479 ± 0.040 mm³/Mc, which was significantly lower than the 5.601 ± 0.456 mm³/Mc for UHMWPE. The excellent mechanical properties and wear resistance of ULWPE were derived from its unique structure. Dynamic rheological assessments and thermal classification techniques confirmed that ULWPE had long-branched chains. The long-branched chains markedly increased the proportion of the high entanglement and the tie molecules in the amorphous regions, endowing it with superior toughness. At the same time, the high crystallinity of ULWPE gives it sufficient hardness and strength. The combination of high crystallinity and high entanglement endowed ULWPE with a good balance between strength and toughness, leading to its exceptional mechanical properties and wear resistance. This study provided robust data for ULWPE's clinical use and theoretical insights for designing durable, implantable polymers.

Background/Aims Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Abstract The study aims to explore the influence of parental over-protection on academic entitlement of nursing students, and examine the mediating roles of external locus of control and psychological entitlement. The study sampled two medical universities in Guizhou and Yunnan provinces, China. Participants were nursing students in grades one to four (N = 1003; mean age = 19.51 years; 81.95% female). Using a structural equation model, we examined the mediating effect of external locus of control and psychological entitlement on parental over-protection and academic entitlement. The results show that there was a significant correlation between all variables, and external locus of control and psychological entitlement played a serial mediating role between parental over-protection and academic entitlement. Our findings suggest that academic entitlement of nursing students can be reduced by adjusting parental rearing behaviors, reducing students’ psychological entitlement, and teaching them how to form a healthier attribution style.

Abstract Background The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. Methods We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. Results CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. Conclusions Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

Abstract Background The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics. Methods The study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9. Results In males, the 97.5th centile NT-proBNP concentration at age

Abstract Background Tricuspid regurgitation (TR) is a common valvular heart disease worldwide, and current guidelines for TR treatment are relatively conservative, as well as with detrimental outcomes. Restoration of sinus rhythm was reported to improve the TR severity in those TR patients with atrial fibrillation (AF). However, relevant research was limited. The aim of this meta-analysis was to evaluate the clinical outcomes of restoration of sinus rhythm in TR patients with AF. Methods In this study, PubMed, Web of Science, and Scopus databases were searched for study enrollment until July 2023. This study was designed under the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. These studies containing the patient’s baseline characteristics, surgical procedure, and at least one of the clinical outcomes were included. The primary endpoint was TR grade during follow-up after restoration of sinus rhythm. Results Out of 1074 records, 6 were enrolled. Restoration of sinus rhythm is associated with a reduction of TR severity (TR grade, odds ratio 0.11, 95% confidence interval (CI): 0.01 to 1.28, P = 0.08, I2 = 83%; TR area, mean difference (MD) -2.19 cm2, 95% CI: -4.17 to -0.21 cm2, P = 0.03, I2 = 96%). Additionally, remolding of right heart with a significant reduction of tricuspid valve annulus diameter (MD -0.36 cm, 95%CI: -0.47 to -0.26 cm, P

ABSTRACT: Adequate energy supply is a crucial factor for maintaining the production performance in cows during the early lactation period. Adding fatty acids (FA) to diets can improve energy supply, and the effect could be related to the chain length and degree of saturation of those FA. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites, and milk FA profile in early lactation dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 days in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in each group. Cows in the 3 treatment groups were provided iso-energy and iso-nitrogen diets, but the C16:0 to cis-9 C18:1 ratios were different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); and (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% on a dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield, and feed efficiency increased linearly with increasing cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, but the percentage of milk total solids and somatic cell count decreased linearly. Although body condition scores were not affected by treatments, body weight loss decreased linearly with increasing cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except for a linear increase in ether extract and neutral detergent fiber digestibility with increasing cis-9 C18:1 ratio. There was a linear increase in the concentration of plasma glucose, but the triglyceride and nonesterified FA concentrations decreased linearly with increasing cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo FA decreased quadratically, but the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio that had the most powerful beneficial effect on early lactation cows was 72.7:27.3 (C16:0 to cis-9 C18:1).

Bone tissue engineering is the main method for repairing large segment bone defects. In this study, a layer of bioactive MgO nanoparticles was wrapped on the surface of spherical Zn powders, which allowed the MgO nanoparticles to be incorporated into 3D-printed Zn matrix and improved the biodegradation and biocompatibility of the Zn matrix. The results showed that porous pure Zn scaffolds and Zn/MgO scaffolds with skeletal-gyroid (G) model structure were successfully prepared by selective laser melting (SLM). The average porosity of two porous scaffolds was 59.3 and 60.0%, respectively. The pores were uniformly distributed with an average pore size of 558.6–569.3 μm. MgO nanoparticles regulated the corrosion rate of scaffolds, resulting in a more uniform corrosion degradation behavior of the Zn/MgO scaffolds in simulated body fluid solution. The degradation ratio of Zn/MgO composite scaffolds in vivo was increased compared to pure Zn scaffolds, reaching 15.6% at 12 weeks. The yield strength (10.8 ± 2.4 MPa) of the Zn/MgO composite scaffold was comparable to that of cancellous bone, and the antimicrobial rate were higher than 99%. The Zn/MgO composite scaffolds could better guide bone tissue regeneration in rat cranial bone repair experiments (completely filling the scaffolds at 12 weeks). Therefore, porous Zn/MgO scaffolds with G-model structure prepared with SLM are a promising biodegradable bone tissue engineering scaffold.

Multi-drug resistant bacterial infections pose a significant threat to human health. Thus, the development of effective bactericidal strategies is a pressing concern. In this study, a ternary heterostructure (Zn–CN/P-GO/BiS) comprised of Zn-doped graphite phase carbon nitride (g-C3N4), phosphorous-doped graphene oxide (GO) and bismuth sulphide (Bi2S3) is constructed for efficiently treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound. Zn doping-induced defect sites in g-C3N4 results in a reduced band gap (ΔE) and a smaller energy gap (ΔEST) between the singlet state S1 and triplet state T1, which favours two-photon excitation and accelerates electron transfer. Furthermore, the formation of an internal electric field at the ternary heterogeneous interface optimizes the charge transfer pathway, inhibits the recombination of electron-hole pairs, improves the photodynamic effect of g-C3N4, and enhances its catalytic performance. Therefore, the Zn–CN/P-GO/BiS significantly augments the production of reactive oxygen species and heat under 808 nm NIR (0.67 W cm−2) irradiation, leading to the elimination of 99.60% ± 0.07% MRSA within 20 min. Additionally, the release of essential trace elements (Zn and P) promotes wound healing by activating hypoxia-inducible factor-1 (HIF-1) and peroxisome proliferator-activated receptors (PPAR) signaling pathways. This work provides unique insight into the rapid antibacterial applications of trace element doping and two-photon excitation.

Utilizing standardized artificial regulatory sequences to fine-tuning the expression of multiple metabolic pathways/genes is a key strategy in the creation of efficient microbial cell factories. However, when regulatory sequence expression strengths are characterized using only a few reporter genes, they may not be applicable across diverse genes. This introduces great uncertainty into the precise regulation of multiple genes at multiple expression levels. To address this, our study adopted a fluorescent protein fusion strategy for a more accurate assessment of target protein expression levels. We combined 41 commonly-used metabolic genes with 15 regulatory sequences, yielding an expression dataset encompassing 520 unique combinations. This dataset highlighted substantial variation in protein expression level under identical regulatory sequences, with relative expression levels ranging from 2.8 to 176-fold. It also demonstrated that improving the strength of regulatory sequences does not necessarily lead to significant improvements in the expression levels of target proteins. Utilizing this dataset, we have developed various machine learning models and discovered that the integration of promoter regions, ribosome binding sites, and coding sequences significantly improves the accuracy of predicting protein expression levels, with a Spearman correlation coefficient of 0.72, where the promoter sequence exerts a predominant influence. Our study aims not only to provide a detailed guide for fine-tuning gene expression in the metabolic engineering of Escherichia coli but also to deepen our understanding of the compatibility issues between regulatory sequences and target genes.

Chronic bioenergetic imbalances and inflammation caused by hyperglycemia are obstacles that delay diabetic wound healing. However, it is difficult to directly deliver energy and metabolites to regulate intracellular energy metabolism using biomaterials. Herein, we propose a light-driven bioenergetic and oxygen-releasing hydrogel (PTKM@HG) that integrates the thylakoid membrane-encapsulated polyphenol nanoparticles (PTKM NPs) to regulate the energy metabolism and inflammatory response in diabetic wounds. Upon red light irradiation, the PTKM NPs exhibited oxygen generation and H2O2 deletion capacity through a photosynthetic effect to restore hypoxia-induced mitochondrial dysfunction. Meanwhile, the PTKM NPs could produce exogenous ATP and NADPH to enhance mitochondrial function and facilitate cellular anabolism by regulating the leucine-activated mTOR signaling pathway. Furthermore, the PTKM NPs inherited antioxidative and anti-inflammatory ability from polyphenol. Finally, the red light irradiated PTKM@HG hydrogel augmented the survival and migration of cells keratinocytes, and then accelerated angiogenesis and re-epithelialization of diabetic wounds. In short, this study provides possibilities for effectively treating diseases by delivering key metabolites and energy based on such a light-driven bioenergetic hydrogel.

Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.