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Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

The benefits of using cryogenic liquid nitrogen shock to enhance coal permeability have been confirmed from experimental perspectives. In this paper, we develop a fully coupled thermo-elastic model in combination with the strain-based isotropic damage theory to uncover the cooling-dominated cracking behaviors through three typical cases, i.e. coal reservoirs containing a wellbore, a primary fracture, and a natural fracture network, respectively. The progressive cracking processes, from thermal fracture initiation, propagation or cessation, deflection, bifurcation to multi-fracture interactions, can be well captured by the numerical model. It is observed that two hierarchical levels of thermal fractures are formed, in which the number of shorter thermal fractures consistently exceeds that of the longer ones. The effects of coal properties related to thermal stress levels and thermal diffusivity on the fracture morphology are quantified by the fracture fractal dimension and the statistical fracture number. The induced fracture morphology is most sensitive to changes in the elastic modulus and thermal expansion coefficient, both of which dominate the complexity of the fracture networks. Coal reservoir candidates with preferred thermal-mechanical properties are also recommended for improving the stimulation effect. Further findings are that there exists a critical injection temperature and a critical in-situ stress difference, above which no thermal fractures would be formed. Preexisting natural fractures with higher density and preferred orientations are also essential for the formation of complex fracture networks. The obtained results can provide some theoretical support for cryogenic fracturing design in coal reservoirs.

The Himalayas and their surrounding areas boast vast glaciers rivaling those in polar regions, supplying vital meltwater to the Indus, Ganges, and Brahmaputra rivers, supporting over a billion downstream inhabitants for drinking, power, and agriculture. With changing runoff patterns due to accelerated glacial melt, understanding and projecting glacio-hydrological processes in these basins is imperative. This review assesses the evolution, applications, and key challenges in diverse glacio-hydrology models across the Himalayas, varying in complexities like ablation algorithms, glacier dynamics, ice avalanches, and permafrost. Previous findings indicate higher glacial melt contributions to annual runoff in the Indus compared to the Ganges and Brahmaputra, with anticipated peak melting in the latter basins — having less glacier cover — before the mid-21st century, contrasting with the delayed peak expected in the Indus Basin due to its larger glacier area. Different modeling studies still have large uncertainties in the simulated runoff components in the Himalayan basins; and the projections of future glacier melt peak time vary at different Himalaya sub-basins under different Coupled Model Intercomparison Project (CMIP) scenarios. We also find that the lack of reliable meteorological forcing data (particularly the precipitation errors) is a major source of uncertainty for glacio-hydrological modeling in the Himalayan basins. Furthermore, permafrost degradation compounds these challenges, complicating assessments of future freshwater availability. Urgent measures include establishing comprehensive in situ observations, innovating remote-sensing technologies (especially for permafrost ice monitoring), and advancing glacio-hydrology models to integrate glacier, snow, and permafrost processes. These endeavors are crucial for informed policymaking and sustainable resource management in this pivotal, glacier-dependent ecosystem.

Background: The anterolateral thigh (ALT) flap plays a crucial role in reconstructive surgeries, providing versatile and reliable soft-tissue coverage. Flap thickness is a critical determinant of tissue volume and quality. Vascular factors, including the vascular diameter of the perforators and the length of the vascular pedicle, significantly influence flap viability and postrepair outcomes. To enhance preoperative assessment, this study integrated gender and body mass index (BMI) to analyze the anatomical characteristics of ALT flaps. Methods: This study used somatic penetrating ultrasonography to examine bilateral ALT flaps in patients. This study analyzed the relationship between gender and ALT flap thickness, vascular diameter of the perforators, and vascular pedicle length. Chi-square test was used to assess variations in age and gender. Multiple t-tests compared flap thickness, vascular diameter, and pedicle length between men and women in different BMI groups. Results: A total of 158 patients were included in this study from January 2018 to December 2022. In BMI < 24 and BMI ≥ 24.0 groups, males had lower ALT flap thickness than females (p < 0.0001 in each subgroup). Similarly, the vascular diameter of the perforators followed the same trend, with females having larger vascular diameters than males in BMI < 24 and BMI ≥ 24.0 groups. In terms of vascular pedicle length, males had longer pedicle length than females in both BMI < 24 and BMI ≥ 24.0 groups (p < 0.05 in each subgroup). Conclusions: Females demonstrate greater ALT flap thickness and larger vascular diameter of the perforators than males, whereas males have a longer length of the vascular pedicle.

Karst fracture-cavity carbonate reservoirs, in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances, have become significant fields of oil and gas exploration and exploitation. Proppant fracturing is considered as the best method for exploiting carbonate reservoirs; however, previous studies primarily focused on the effects of individual types of geological formations, such as natural fractures or cavities, on fracture propagation. In this study, true-triaxial physical simulation experiments were systematically performed under four types of stress difference conditions after the accurate prefabrication of four types of different fracture-cavity distributions in artificial samples. Subsequently, the interaction mechanism between the hydraulic fractures and fracture-cavity structures was systematically analyzed in combination with the stress distribution, cross-sectional morphology of the main propagation path, and three-dimensional visualization of the overall fracture network. It was found that the propagation of hydraulic fractures near the cavity was inhibited by the stress concentration surrounding the cavity. In contrast, a natural fracture with a smaller approach angle (0° and 30°) around the cavity can alleviate the stress concentration and significantly facilitate the connection with the cavity. In addition, the hydraulic fracture crossed the natural fracture at the 45° approach angle and bypassed the cavity under higher stress difference conditions. A new stimulation effectiveness evaluation index was established based on the stimulated reservoir area (SRA), tortuosity of the hydraulic fractures (T), and connectivity index (CI) of the cavities. These findings provide new insights into the fracturing design of carbonate reservoirs.

Geotechnical engineering data are usually small-sample and high-dimensional, which brings a lot of challenges in predictive modeling. This paper uses a typical high-dimensional and small-sample swell pressure (Ps) dataset to explore the possibility of using multi-algorithm hybrid ensemble and dimensionality reduction methods to mitigate the uncertainty of soil parameter prediction. Based on six machine learning (ML) algorithms, the base learner pool is constructed, and four ensemble methods, Stacking (SG), Blending (BG), Voting regression (VR), and Feature weight linear stacking (FWL), are used for the multi-algorithm ensemble. Furthermore, the importance of permutation is used for feature dimensionality reduction to mitigate the impact of weakly correlated variables on predictive modeling. The results show that the proposed methods are superior to traditional prediction models and base ML models, where FWL is more suitable for modeling with small-sample datasets, and dimensionality reduction can simplify the data structure and reduce the adverse impact of the small-sample effect, which points the way to feature selection for predictive modeling. Based on the ensemble methods, the feature importance of the five primary factors affecting Ps is the maximum dry density (31.145%), clay fraction (15.876%), swell percent (15.289%), plasticity index (14%), and optimum moisture content (13.69%), the influence of input parameters on Ps is also investigated, in line with the findings of the existing literature.

Pseudorabies (PR) is an acute infectious disease of pigs caused by the PR virus (PRV) and results in great economic losses to the pig industry worldwide. PRV glycoprotein E (gE)-based enzyme-linked immunosorbent assay (ELISA) has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some countries. Nanobody has the advantages of small size and easy genetic engineering and has been a promising diagnostic reagent. However, there were few reports about developing nanobody-based ELISA for detecting anti- PRV-gE antibodies. In the present study, the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian camel. Then, two nanobodies against PRV-gE were screened from the immunized camel by phage display technique. Subsequently, two nanobody-HRP fusion proteins were expressed with HEK293T cells. The PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA (bELISA) to detect anti-PRV-gE antibodies. Through optimizing the conditions of bELISA, the amount of coated antigen was 200 ng per well, and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:5. The cut-off value of bELISA was 24.20%, and the sensitivity and specificity were 96.43 and 92.63%, respectively. By detecting 233 clinical pig sera with the developed bELISA and a commercial kit, the results showed that the coincidence rate of two assays was 93.99%. Additionallly, epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV strains. Simple, great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were developed. The bELISA could be used for monitoring and eradicating PR.

Objective: This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer (CRC) patients in Fudan University Shanghai Cancer Center (FUSCC). Methods: This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020. Patients were divided into five groups for different analytical purposes: (1) the before vs. since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients; (2) the partial vs. total mesorectal excision (TME) groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients; (3) the tumor deposit (TD)(+)N0 vs. TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis (LNM); (4) the before vs. since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients; and (5) the groups with vs. without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients. Patients’ clinicopathological parameters, including age at diagnosis, sex, tumor size, location, differentiation, mucinous subtype, TD, lymphovascular invasion, perineural invasion, tumor depth, LNM and distant metastasis, and tumor-node-metastasis (TNM) stage, were compared between groups. Kaplan-Meier analysis with log rank method was performed for patients’ overall survival (OS) and disease-free survival (DFS) analyses. Results: In pathological reports, there were three parameter changes that impacted patient outcomes. Firstly, changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1: 110.9 to 1: 0.26. In comparison to patients admitted before 2014 (n = 4,754), a significant difference in prognosis between pT3 and pT4 stages was observed since 2014 (n = 9,965). Secondly, we began to evaluate the completeness of the mesorectum since 2016. As a result, 91.0% of patients with low rectal cancer underwent TME (n = 4,111) surgery, and patients with TME had significantly better OS compared with partial mesorectal excision (PME, n = 409). Thirdly, we began to stage TD (+) LNM (-) as N1c since 2017. The results showed that N1c (n = 127) but not N0 (n = 39) can improve the prognosis of patients without LNM and distal metastasis. In molecular testing, there have been three and five iterations of updates regarding mismatch repair (MMR)/microsatellite instability (MSI) status and RAS/BRAF gene mutation detection, respectively. The standardization of MMR status testing has sharply decreased the proportion of deficient MMR (dMMR) patients (from 32.5% to 7.4%) since 2013. The prognosis of patients underwent MMR status testing since 2013 (n = 867) were significantly better than patients before 2013 (n = 1,313). In addition, detection of RAS/BRAF gene mutation status (n = 5,041) resulted in better DFS but not OS, for patients with stage I-III disease (n = 16,557). Conclusion: Over the past few decades, updates in elements in pathological reports, as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.

Chemical exposure and local hypoxia caused by mask-wearing may result in skin physiology changes. The effects of methylparaben (MeP), a commonly used preservative in personal care products, and hypoxia on skin health were investigated by HaCaT cell and ICR mouse experiments. MeP exposure resulted in lipid peroxidation and interfered with cellular glutathione metabolism, while hypoxia treatment disturbed phenylalanine, tyrosine, and tryptophan biosynthesis pathways and energy metabolism to respond to oxidative stress. A hypoxic environment increased the perturbation of MeP on the purine metabolism in HaCaT cells, resulting in increased expression of proinflammatory cytokines. The synergistic effects were further validated in a mouse model with MeP dermal exposure and “mask-wearing” treatment. CAT, PPARG, and MMP2 were identified as possible key gene targets associated with skin health risks posed by MeP and hypoxia. Network toxicity analysis suggested a synergistic effect, indicating the risk of skin inflammation and skin barrier aging.

Background: Patients with fractures of the proximal humerus often local complications and failures attributed to osteoporosis. Currently, there is a lack of straight forward screening methods for assessing the extent of local osteoporosis in the proximal humerus. This study utilizes machine learning techniques to establish a diagnostic approach for evaluating local osteoporosis by analyzing the patient's demographic data, bone density, and X-ray ratio of the proximal humerus. Methods: A cohort comprising a total of 102 hospitalized patients admitted during the period spanning from 2021 to 2023 underwent random selection procedures. Resulting in exclusion of 5 patients while enrolling 97 patients for analysis encompassing patient demographics, shoulder joint anteroposterior radiographs, and bone density information. Using the modified Tingart index methodology involving multiple measurements denoted as M1 through M4 obtained from humeral shafts. Within this cohort comprised 76 females (78.4 %) and 21 males (21.6 %), with an average age of 73.0 years (range: 43–98 years). There were 25 cases with normal bone density, 35 with osteopenia, and 37 with osteoporosis. Machine learning techniques were used to randomly divide the 97 cases into training (n = 59) and validation (n = 38) sets with a ratio of 6:4 using stratified random sampling. A decision tree model was built in the training set, and significant diagnostic indicators were selected, with the performance of the decision tree evaluated using the validation set. Multinomial logistic regression methods were used to verify the strength of the relationship between the selected indicators and osteoporosis. Results: The decision tree identified significant diagnostic indicators as the humeral shaft medullary cavity ratio M2/M4, age, and gender. M2/M4 ≥ 1.13 can be used as an important screening criterion; M2/M4 < 1.13 was predicted as local osteoporosis; M2/M4 ≥ 1.13 and age ≥83 years were also predicted as osteoporosis. M2/M4 ≥ 1.13 and age

In the system-level simulations of heat transfer systems, the characteristics of heat exchangers are often considered constant or used in empirical formulas, which affect the accuracy of the system model. Herein a multi-scale simulation method to analyze the heat transfer characteristics of a thermal management system, including an intermediate loop is proposed. The system model is developed based on the heat current method and flow resistance models. By applying COMSOL LiveLink for MATLAB module, a multi-scale model is obtained, which combines three-dimensional numerical models of the heat exchangers with the system model. Compared to the experimental results, the relative errors associated with the outlet temperatures and heat transfer rate are less than 1.1% and 8.2 %, respectively, thus validating the model. Discussions on the effects of the geometric structure of the heat exchangers on the system show that a plate heat exchanger with 12 plates and a plate spacing of 8 mm is better. For achieving systematic maximum heat dissipation for a certain pumping power consumption, a multi-scale optimization method is proposed by coupling the Lagrange function and numerical model. The results show that the total heat transfer rate improves by 5.89 %, from 8314.81 W to 8804.35 W.

Under the dual pressures of rapid urbanization and global warming, the management of solar radiation has become an urgent issue to address. In this context, the potential regulatory role of urban street networks on solar radiation has garnered widespread attention. However, existing research lacks an understanding of the impact of street direction. By utilising street view data and solar trajectory simulation technology, it becomes possible to facilitate the revelation of spatiotemporal differences in solar radiation across streets with different direction. The results show that solar radiation is generally lower on north–south streets than on east–west streets. In terms of spatial differences, the average solar radiation in the fifth ring of Beijing is 25.38% higher than that in the second ring. Temporally, the average solar radiation in August, the highest month, is 15.98% greater than in October, the lowest month. Additionally, solar radiation on east–west street direction shows more intense variations in summer. A periodic variation in solar radiation was also discovered in relation to street angles, with different frequencies and amplitudes at 30° and 180°. This study is the first to focus on the directional attributes of roads at an urban scale. By utilising 100,000 street view images, it calculates and analyses the spatiotemporal distribution of solar radiation in Beijing during summer across different direction. The findings provide new insights into the relationship between the distribution of solar radiation and the morphology of urban roads.

This study aims to elucidate the mechanism underlying the reduced jejunal injury in PEDV-challenged piglets after oral administration of puerarin and poria cocos polysaccharides combination (PR + PCP, PP). Results showed that the PEDV challenge caused damage to the small intestine by injuring the villi and inducing redox imbalance which exacerbated the diarrhea of piglets, while PP administration trended to reduce the PEDV infection-caused diarrhea in piglets by alleviating the jejunal injury and restoring the redox balance. Further proteomics and qPCR results showed that PP could significantly reduce the decline of the protein and mRNA levels of gene SDSL inhibiting cellular autophagy in PEDV-infected jejunum of piglets. The immunofluorescence results showed that the autophagy levels of the jejunum expressing low SDSL caused by PEDV infection in the PEDV group were significantly higher than those of the jejunum expressing higher levels of SDSL caused by PP administration in the PP + PEDV group. These results showed that PEDV infection caused jejunal excessive autophagy in piglets by reducing the expression level of SDSL. However, the restoration of the expression level of SDSL significantly reduced the PEDV infection-caused jejunal excessive autophagy in piglets, leading to a decrease in jejunal injury. Therefore, PP administration can alleviate the excessive autophagy-caused jejunal injury by increasing SDSL levels in PEDV-infected piglets. This result suggests that PP can be used as a potential feed additive to prevent PEDV infection.

The consumption value seems to be insufficient to explain consumers' domestic electric vehicle purchase behaviour, especially in a highly competitive global environment. This study aims to investigate how consumer ethnocentrism and perceived interactivity influence consumption value and pro-environmental value, subsequently affecting attitude and intention. A total of 353 valid questionnaires were collected through convenience sampling in Xuzhou, China, and the partial least square (PLS) path modelling approach was performed to test the hypotheses. The results show that consumer ethnocentrism and perceived interactivity positively influence function value, emotional value, and social value; perceived interactivity also positively influences altruistic value, biospheric value, and collectivistic value. Function value, social value, and collectivistic value positively influence attitude; however, emotional value, altruistic value and biospheric value did not find a correlation with attitude. Furthermore, attitude positively influences intention to adopt domestic electric vehicles. Finally, the theoretical and practical implications, as well as limitations were discussed accordingly.

Heat stress (HS) can lead to oxidative stress and inflammatory responses, which jeopards animal production. Enzymatically treated mulberry leaf protein (ETMLP) has antioxidant activities and immune regulation. This study aimed to investigate the impacts of ETMLP on mitigate liver injury caused by heat stress in animals. All 25 rats were divided into five groups: control, heat stress, and three ETMLP supplementation groups (HS + 0.4 %, HS + 0.8 %, and HS + 1.2 %). ETMLP supplementation effectively reduced markers of liver damage and increasing the level of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px). It also regulated protein expression associated with stress response and antioxidant defense and suppressed pro-inflammatory proteins and pathways expression. Moreover, ETMLP improved intestinal morphology and increased the intestinal barrier gene abundance. ETMLP also positively influenced the intestinal microbiota by increasing beneficial microorganisms. Overall, ETMLP reversed heat stress-induced damage, improved growth performance, and regulated the intestinal microbiota in the study animals.

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.

Elastic turbulence has emerged as a promising method to enhance heat transfer performance at the microscale. However, previous studies have mainly focused on the overall convective heat transfer performance in curved channels, overlooking the fact that the chaotic flow intensity varies along the streamline, leading to diverse local heat transfer characteristics. In this study, we systematically investigate the hydraulic and thermal properties of a dilute polymer solution under elastic turbulence conditions, where the inflow conditions exhibit a vanishing Reynolds number (Re) and high Weissenberg number (Wi), enabling a comprehensive understanding of the influence of polymers on the system. Through extensive direct numerical simulations using Rheotool, a two-dimensional curvilinear channel flow of an Oldroyd-B viscoelastic fluid is analyzed. By examining the variations of the friction factor and Nusselt number along the serpentine channel, we unveil both global and local characteristics of elastic turbulence. Based on the Wi value, we identify three distinct regimes. In the first regime (05), we observe a remarkable heat transfer enhancement of up to 60% along with a reduced friction factor. The significant enhancement of heat transfer with increasing Wi can be attributed to the intensifying elastic instability resulting from the balance between normal stresses and streamlined curvatures.

The ejector refrigeration technology driven by low-grade heat sources constitutes as one of the crucial means to solve the energy shortage in present-day society and to reduce the global environmental pollution. Thermodynamics ejector models are the basis of performance prediction, system control and structural design in ejector refrigeration systems driven by low-grade heat sources. However, the majority of present ejector models are unable to simultaneously meet the general feasibility of full operating conditions and the level of prediction accuracy for improving the energy efficiency of the refrigeration system. In this study, a novel theoretical model of ejectors is successfully derived based on the foundation of compound-choking theory and gas dynamic relations, which easily predicts the entrainment performance under the on-design and off-design conditions in ejector refrigeration systems. Indeed, a direct solution algorithm is presented to quickly and accurately solve this model and a linear correlation is employed between the mixing loss coefficient and the back pressure at the subcritical mode. The developed model is verified with experimental results in R245fa, R134a and R600a ejector refrigeration system. The results show that the model provides a precise estimation of the entrainment performance with the mean relative errors of 2.45 %, 5.49 % and 3.67 % for R245fa, R134a and R600a refrigerants at full working conditions, while the prediction of critical condensing temperatures is considerably approximated by the experimental measurements. In the comparative analysis with the previous model, this model demonstrates a superior prediction performance, especially in the subcritical mode using the linear function mixing loss coefficient. This study will be a valuable aid in the improvement of energy efficiency in ejector refrigeration systems.

Metformin (MET), a commonly prescribed medication for managing type 2 diabetes, has demonstrated various beneficial effects beyond its primary anti-diabetic efficacy. However, the mechanism underlying MET activity and its distribution within organelles remain largely unknown. In this study, we integrate multiple technologies, including chemical labeling, immunostaining, and high-resolution microscopy imaging, to visualize the accumulation of MET in organelles of cultured cells. To achieve this objective, an alkynylated MET probe is developed that preserves biological activity similar to biguanide drugs. As determined by biorthogonal chemical labeling and imaging, the MET probe selectively localizes to substructures within cells, contrasting with its probe control. Furthermore, the MET probe can be competitively and efficiently washed out through biguanide administration, demonstrating the specific activity of this probe in monitoring the cellular dynamics of biguanide drugs. Our results indicate that the MET probe can reach near-saturated concentrations within 2 h and is rapidly eliminated within an additional 2 h once the exogenous source of the drug is removed. Furthermore, we reveal that the MET probe primarily accumulates in mitochondria, particularly within the mitochondrial matrix, and has a minor presence in other organelles, such as lysosomes and endosomes. Together, this study provides the first view of the subcellular localization of MET and lays the foundation for future investigations on its molecular targets and mechanisms of action in promoting human health.

Summary: Styles and stigmas are crucial components of the fertilization process that allows a pear tree to bear fruit. The information regarding the development mechanism of pear style and stigma is still unclear. Our results demonstrated that IAA, ABA, and BR are significantly increased at 1 DBF, while JA is decreased at 5 DBF. The fructose and starch contents significantly increased at 1 DBF when the style with stigma was ready for pollination. Transcriptome and DNA methylation analysis showed 8087 DEGs and 3771 DMRs were enriched in plant hormones biosynthesis, carbohydrate biosynthesis and metabolism, and TFs in 1 DBF as compared with 7 DBF. The CHH methylation type of DMRs accounts for 84.75%. Most DMRs of CHH upregulated in 1 DBF vs. 7 DBF. This study found for the first time that transcription factor ERFs and DNA methylation are involved in regulating the growth and development of fruit plant style and stigma.

Summary: The digital and social network revolution in the fitness industry will provide consumers with opportunities to achieve their healthy and active lifestyle goals both online and offline. The online fitness communities provide us an ideal context for the health behavior research with behavioral logs and user-generated content. Enhanced user profiles can empower platform operators to implement more tailored recommendations, thereby enhancing the efficiency of precision marketing and fitness promotion. This study aims to accurately construct user profiles for Chinese online fitness community users and provide future health promotion strategies accordingly. We propose a novel approach that integrates explicit behavior logs and implicit user preferences to accurately construct user profiles. Our findings indicate that users primarily prioritize fitness benefits, incentives, and decision-making. Our results demonstrate the relationship between fitness behavior and implicit preferences, suggesting that promoting fitness behavior can be achieved through streamlining decision-making processes, establishing incentive communities, and emphasizing benefits.

Small cell lung cancer (SCLC) is a fatal tumor type that is prone to drug resistance. In our previous study, we showed that human rhomboid-5 homolog-1 (RHBDF1) was differentially expressed in 5 intrinsic cisplatin-resistant SCLC tissues compared with 5 intrinsic cisplatin-sensitive SCLC tissues by RNA sequencing, which intrigued us. We performed gain- and loss-of-function experiments to investigate RHBDF1 function, bioinformatics analysis, qRT-PCR, western blotting, and immunoprecipitation to elucidate the molecular mechanisms as well as detect RHBDF1 expression in SCLC by immunohistochemistry. We found that RHBDF1 knockdown promoted cell proliferation and cisplatin chemoresistance and inhibited apoptosis in vitro and in vivo. These effects could be reversed by overexpressing RHBDF1 in vitro. Mechanistically, RHBDF1 interacted with YAP1, which increased the phosphorylation of Smad2 and transported Smad2 to the nucleus. Among clinical specimens, the RHBDF1 was a low expression in SCLC and was associated with clinicopathological features and prognosis. We are the first to reveal that RHBDF1 inhibited cell proliferation and promoted cisplatin sensitivity in SCLC and elucidate a novel mechanism through RHBDF1/YAP1/Smad2 signaling pathway which played a crucial role in cisplatin chemosensitivity. Targeting this pathway can be a promising therapeutic strategy for chemotherapy resistance in SCLC.

Gas explosion accidents are a leading cause of casualties in underground coal mines. This study investigates the variation patterns of explosion temperature and pressure under different initial gas concentration conditions using a 20 L explosion characteristic test system and high-precision sensors. Accurate post-explosion gas analyses were conducted using a GC9560 gas chromatograph. Our research aligns with global research, finding that initial gas concentrations within the range of 5.8%–13.3% generate maximum explosion pressures between 0.3 and 0.9 MPa, posing a significant overpressure hazard to humans. Comprehensive fitting analyses of various post-explosion gases reveal that at an initial gas concentration of 10.6%, the produced H2 can reach its lower explosion limit, indicating a risk of secondary explosions. Furthermore, post-explosion CO levels can peak at 9.87%, potentially causing poisoning or death, while elevated CO2 levels and diminished O2 concentrations could lead to asphyxiation. A unique observation at a 9.5% concentration was a secondary temperature rise, with the relationship between temperature delay, heating time, and initial gas concentration presenting a U-shaped pattern that mirrors theoretical expectations. This study advances the field by addressing research gaps in post-explosion gas analysis and emphasizing the necessity of precise monitoring and control of gas concentrations, thereby offering novel insights and substantial theoretical and practical contributions to the prevention of gas explosion incidents in underground coal mines.

The temperature of a motor significantly affects its control and lifespan. However, due to the influence of motor structure and operating environment, precise temperature measurement of the motor is challenging with temperature sensors. Therefore, machine learning algorithms are often employed to predict the temperature more accurately. To enhance motor control, integrating machine learning algorithm models with the actual motor control terminal is highly beneficial. This paper proposes a Short and Long Term Memory (LSTM) algorithm model based on Harris's hawk optimization to predict the temperature of the motor stator, which is applied in actual motor control. Furthermore, it evaluates the tracking performance of motor control current. Firstly, an experimental platform for temperature measurement is established to acquire the temperature at different positions of the motor as raw data. Subsequently, the raw data is inputted into three algorithms: LSTM, PSO-LSTM, and HHO-LSTM, for comparison. By comparing evaluation metrics, it is demonstrated that HHO-LSTM exhibits excellent predictive performance. Furthermore, utilizing diverse segments of the motor as model input sets enhances the generalization capability and predictive accuracy of the model. Finally, applied in actual motor control, a comparative analysis of q-axis and d-axis currents reveals reduced fluctuation errors, showcasing improved motor control effectiveness.

For the purpose of enhancing the utilization rate of limestone powder (LP) in concrete and maximizing its activity effect. In this paper, the replacement methods for replacing fly ash (FA) with fine particles and manufactured sand (MS) with coarse particles were proposed. The content of LP replacing FA increased from 10% to 50%, and the content of LP replacing MS increased from 5% to 20%. The effects of LP replacing FA alone, replacing MS alone and particle-screened LP replacing both FA and MS on the workability, mechanical properties, durability of concrete were compared. Analysis of variance (Anova) was used to determine the importance level of the test parameters on the performance characteristics of concrete. The results suggested that LP replacing MS improved the workability and strength of concrete, and ameliorated the carbonation and chloride ion permeability resistance. However, the amount of LP substitution was very low, only 10%. Compared with LP replacing FA alone, the screened substitution improved the cohesion and water retention of concrete. The improvement in strength at 7 and 28 days was better, which was 1.6 MPa and 1.3 MPa higher than replacing FA alone. And there was no significantly adverse effect on the durability of concrete. Moreover, it was conducive to enhancing the utilization rate of LP. According to the research results, the effect of the interaction between LP content and the mixing method on the performance of concrete cannot be ignored. In addition, the screened substitution method was more environmentally friendly and economical, because it was conducive to the recycling of solid waste and landfill waste treatment.

Different driving forces govern the formation of distinct types of oil and gas accumulation and yield diverse oil and gas distributions. Complex oil and gas reservoirs in basins are commonly formed by the combination of multiple forces. It is very difficult but essential to identify driving forces and evaluate their contributions in predicting the type and distribution of oil and gas reservoirs. In this study, a novel method is proposed to identify driving forces and evaluate their contribution based on the critical conditions of porosity and permeability corresponding to buoyancy-driven hydrocarbon accumulation depth (BHAD). The application of this method to the Nanpu Sag of the Bohai Bay Basin shows that all oil and gas accumulations in the reservoirs are jointly formed by four driving forces: buoyance (I), non-buoyance (II), tectonic stress (III1) and geofluid activity (III2). Their contributions to all proven reserves are approximately 63.8%, 16.2%, 2.9%, and 17.0%, respectively. The contribution of the driving forces is related to the depth, distance to faults and unconformity surfaces. Buoyancy dominates the formation of conventional reservoirs above BHAD, non-buoyant dominate the formation of unconventional reservoirs below BHAD, tectonic stress dominates the formation of fractured reservoirs within 300 m of a fault, and geofluids activity dominates the formation of vuggy reservoirs within 100 m of an unconformity surface.

Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN progression. Triterpenoid saponin from Aralia taibaiensis (sAT) has been reported to possess anti-diabetic and anti-oxidant effects. The aim of this study was to examine the influence of sAT on DN treatment and elucidate potential underlying mechanisms. A high-fat diet (HFD) and Streptozotocin (STZ) were employed to induce DN in male Sprague Dawley (SD) rats which were subsequently treated with varying concentrations of sAT for 8 weeks. Our findings reveal that different doses of sAT significantly mitigated hyperglycemia, reduced urinary albumin excretion, and decreased plasma creatinine and blood urea nitrogen levels in DN rats. Moreover, sAT administration improved body weight, alleviated renal fibrosis and histopathological changes in the diabetic kidneys. Notably, sAT treatment partially restored increased Bax expression and decreased Bcl-2 expression. Additionally, sAT inhibited ER stress-related proteins, including GRP78, p-PERK, ATF4 and CHOP in kidneys of DN rats. These results suggest that sAT ameliorated experimental diabetic nephropathy, at least in part, through ER stress pathway. These findings provide a scientific basis for the potential development of sAT as a therapeutic agent for DN treatment.

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer. However, the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations. Furthermore, monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors. In this study, based on our discovery that spore shell (SS) of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity, we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy, chemodynamic therapy and antitumor immunity for synergistic cancer treatment. In detail, SS is separated from probiotic spores and then attached to the surface of liposome (Lipo) that was loaded with hemoglobin (Hb), glucose oxidase (GOx) and JQ1 to construct SS@Lipo/Hb/GOx/JQ1. In tumor tissue, highly toxic hydroxyl radicals (•OH) are generated via sequential catalytic reactions: GOx catalyzing glucose into H2O2 and Fe2+ in Hb decomposing H2O2 into •OH. The combination of •OH and SS adjuvant can improve tumor immunogenicity and activate immune system. Meanwhile, JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response. In this manner, SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis. To summarize, the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the toxic effects and mechanisms of MPs have mostly been conducted in animal models or in vitro cell cultures, which have limitations regarding inter-species differences or stimulation of cellular functions. Organoid technology derived from human pluripotent or adult stem cells has broader prospects for predicting the potential health risks of MPs to humans. Herein, we reviewed the current application advancements and opportunities for different organoids, including brain, retinal, intestinal, liver, and lung organoids, to assess the human health risks of MPs. Organoid techniques accurately simulate the complex processes of MPs and reflect phenotypes related to diseases caused by MPs such as liver fibrosis, neurodegeneration, impaired intestinal barrier and cardiac hypertrophy. Future perspectives were also proposed for technological innovation in human risk assessment of MPs using organoids, including extending the lifespan of organoids to assess the chronic toxicity of MPs, and reconstructing multi-organ interactions to explore their potential in studying the microbiome-gut-brain axis effect of MPs.

Background: Respiratory-triggered (RT) and breath-hold are the most common acquisition modalities for magnetic resonance cholangiopancreatography (MRCP). The present study compared the three different acquisition modalities for optimizing the use of MRCP in patients with diseases of the pancreatic and biliary systems. Materials and methods: Three MRCP acquisition modalities were used in this study: conventional respiratory-triggered sampling perfection with application-optimized contrasts using different flip evolutions (RT-SPACE), modified RT-SPACE, and breath-hold (BH)-SPACE. Fifty-eight patients with clinically suspected pancreatic and biliary system disease were included. All image data were acquired on a 1.5 T MR. Scan time and image quality were compared between the three acquisition modalities. Friedman test, which was followed by post-hoc analysis, was performed among triple-scan protocol. Results: There was a significant difference in the mean acquisition time among conventional RT-SPACE, modified RT-SPACE, and BH-SPACE (167.41±32.11 seconds vs 50.84±73.78 seconds vs 18.00 seconds, P 0.05) among the 3 groups regarding quality of overall image, image clarity, background inhibition, and visualization of the pancreatic and biliary system. Conclusions: MRCP acquisition with the modified RT-SPACE sequence greatly shortens the acquisition time with comparable quality images. The MRCP acquisition modality could be designed based on the patient's situation to improve the examination pass rate and obtain excellent images for diagnosis.

Assessing riverine pollutant loads is a more realistic method for analysing point and non-point anthropogenic pollution sources throughout a watershed. This study compares numerous mathematical modelling strategies for estimating riverine loads based on the chosen water quality parameters: Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Suspended Solids (SS), and Ammoniacal Nitrogen (NH3–N). A riverine load model was developed by employing various input variables including river flow and pollutant concentration values collected at several monitoring sites. Among the mathematical modelling methods employed are artificial neural networks with feed-forward backpropagation algorithms and radial basis functions. The classical multiple linear regression (MLR) statistical model was used for the comparison. Four widely used statistical performance assessment metrics were adopted to evaluate the performance of the various developed models: the root mean square error (RMSE), mean absolute error (MAE), mean relative error (MRE), and coefficient of determination (R2). The considerable number of errors (with RMSE, MAE, and MRE) discovered in estimating riverine loads using the multiple linear regression (MLR) statistical model can be attributed to the nonlinear relationship between the independent variables (Q and Cx) and dependent variables (W). The feed-forward neural network model with a backpropagation algorithm and Bayesian regularisation training algorithm outperformed the radial basis neural network. This finding implies that, in addition to suspended sediment loads, riverine loads may be predicted using an artificial neural network using pollutant concentration (Cx) and river discharge (Q) as input variables. Other geographical and temporal fluctuation characteristics that may impact river water quality, on the other hand, may be incorporated as input variables to enhance riverine load prediction. Finally, riverine load analyses were successfully conducted to reduce the riverine load.

Silver nanoparticles, because of their large absorption surface and small size, are considered to be intelligent magnetic particles. The advancements in nanotechnology have revolutionized cancer treatment, with silver nanoparticles playing a crucial role in this field. In a recent experiment, the effects of Ag nanoparticles formulated from Origanum majorana on breast cancer cells were investigated. It was found that these nanoparticles induce apoptosis through the signal transducer and activator of transcription 3 and P53 signaling pathways. The nanoparticle characterization was conducted using FE-SEM, XRD, and UV–Vis techniques. Furthermore, the Ag nanoparticles exhibited significant antioxidant activity by preventing 50% of DPPH at 183 μg/mL. The MTT assay revealed the anti-breast carcinoma properties of silver NPs on MCF-7, T-47D, and SkBr3 cells. The outcomes demonstrated that as the nanoparticle concentration increased, the cancer cells survival percentage reduced for 3 days. The most effective anticancer effect was observed at 1000 μg/ml. MTT findings indicate that a concentration of nanoparticles at IC50 = 97, 186, and 180 μg/ml effectively targets 50% of MCF-7, T-47D, and SkBr3 breast carcinoma cells. The presence of silver NPs induces cell apoptosis, which is with the Bax markers regulation and the pro-apoptotic cleaved caspase-8 upregulation, while the anti-apoptotic Bcl-2 marker is downregulated. Besides, silver NPs inhibit the formation of colonies. Molecular pathway analysis of breast cells treated with silver NPs reveals an increase in p53 expression, while the total and phosphorylated STAT3 expression is inhibited, suggesting that p53 and STAT3 have a notable role in the remedial efficacies of silver NPs on breast carcinoma cells. Additionally, the Ag nanoparticles exhibit high sensitivity in the hydrazine electrochemical detection, a potentially carcinogenic substance, with a detection limit of 0.25 μM. The developed sensor, utilizing Ag nanoparticles, shows great promise for the environmental monitoring of hydrazine due to its excellent catalytic performance and simple preparation process. Based on clinical research, recent silver nanoparticles have emerged as a viable option for breast cancer treatment.

A novel Mg-Nd-Sm-Zn-Zr alloy with promising age-strengthening effects has been successfully developed to meet the urgent needs of lightweight in the aerospace industry. The precipitation behavior and elastic properties of the nano-precipitates in the alloy have been revealed using transmission electron microscopy and first-principles calculation. The Guinier-Preston (GP) zones, lamellar γ′ precipitates, and granular β′ precipitates formed in the α-Mg matrix after aging at 190 °C for 3 h (under-aging stage). Notably, the alloy reached the peak-aging stage and achieved an excellent ultimate tensile strength of 266 MPa after aging for 18 h. These precipitates further transformed into the lamellar β′ and β1 precipitates, and the enclosed nano-strengthening structure was constructed by γ′, β′ and β1 precipitates. The precipitation sequence of the aged alloy was determined as the supersaturated solid solution (SSSS) → GP zones → β′/γ′ → β1. First-principles calculations and 3D visualization approach demonstrated that the addition of mixed light RE elements can effectively improve the elastic modulus and reduce the elastic anisotropy of β′ nano-precipitates. The Young's modulus (E), shear modulus (G), and anisotropy index (AU) of β′-Mg7(Nd,Sm) precipitates were 48.38 MPa, 18.79 MPa and 2.29, respectively. This study provides a theoretical and experimental basis for further research and development of novel high-performance Mg-light RE alloys.

Phosphorus (P) is a nonrenewable resource and a critical element for plant growth that plays an important role in improving crop yield. Excessive P fertilizer application is widespread in agricultural production, which not only wastes phosphate resources but also causes P accumulation and groundwater pollution. Here, we hypothesized that the apparent P balance of a crop system could be used as an indicator for identifying the critical P input in order to obtain a high yield with high phosphorus use efficiency (PUE). A 12-year field experiment with P fertilization rates of 0, 45, 90, 135, 180, and 225 kg P2O5 ha−1 was conducted to determine the crop yield, PUE, and soil Olsen-P value response to P balance, and to optimize the P input. Annual yield stagnation occurred when the P fertilizer application exceeded a certain level, and high yield and PUE levels were achieved with annual P fertilizer application rates of 90–135 kg P2O5 ha−1. A critical P balance range of 2.15–4.45 kg P ha−1 was recommended to achieve optimum yield with minimal environmental risk. The critical P input range estimated from the P balance was 95.7–101 kg P2O5 ha−1, which improved relative yield (>90%) and PUE (90.0–94.9%). In addition, the P input–output balance helps in assessing future changes in Olsen-P values, which increased by 4.07 mg kg−1 of P for every 100 kg of P surplus. Overall, the P balance can be used as a critical indicator for P management in agriculture, providing a robust reference for limiting P excess and developing a more productive, efficient and environmentally friendly P fertilizer management strategy.

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Since the geopolitical conflict between Russia and Ukraine, Western countries led by the United States and the European Union have launched several energy sanctions against Russia. How will sanctions and countersanctions on energy trade affect the EU-Russia and the world’s energy trade pattern? This paper sets six energy trade scenarios based on the degree of energy sanctions and counter-sanction measures imposed by the EU and Russia. We use the global multi-region comparative static CGE model to simulate the changes in macroeconomic indicators in major countries worldwide. The diversion effect of energy trade and the impact on the national economy caused by geographical risks quantitatively analyzes. The results show: (1) Energy sanctions will cause economic damage to both sides, in the worst-case scenario, the EU economic loss reaches 1.488%, the Russian loss reaches 4.8%, and worldwide inflation will rise; (2) Russia’s counter-sanctions will have a direct economic impact on the EU, but will not improve its economic situation; (3) Energy sanctions will bring about a direct energy trade transfer effect, the EU’s energy imports will be diverted to non-Russian markets, and Russian energy exports will also shift to Asian markets, and energy trade between the two economies will be significantly reduced; (4) Energy supply will have a profound impact on the world’s economy and society, leading to social instability and a decline in total output of 2.895%. Energy games will have a negative impact on the world’s carbon emission reduction and energy consumption structure transformation. Through quantitative analysis of the impact of energy sanctions on the world economy and society, the energy game caused by the geopolitical crisis will harm both parties involved in the game and the world economy. The world pattern will return from the development pattern of cooperative division of labor to a situation of conflict and confrontation, which is not conducive to the transformation of energy trade and consumption structure under market rules.

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16 hours of fasting and 8 hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia.

Dynamic monitoring of surface water bodies is essential for understanding global climate change and the impact of human activities on water resources. Satellite remote sensing is characterized by large-scale monitoring, timely updates, and simplicity, and it has become an important means of obtaining the distribution of surface water bodies. This study is based on a long time-series Landsat satellite images and the Google Earth Engine (GEE) platform, focusing on Anhui Province in China, and proposes a method for extracting surface water that combines water indices, Bias-Corrected Fuzzy Clustering Method (BCFCM), and OTSU threshold segmentation. The spatial distribution of surface water in Anhui Province was obtained from 1984 to 2021, and further analysis was conducted on the spatiotemporal characteristics of surface water in each city and three major river basins within the province. The results indicated that the overall accuracy of water extraction in this study was 94.06 %. Surface water in Anhui was most abundant in 1998 and least in 2001, with more distribution in the south than in the north. Northern Anhui is dominated by rivers, while southern Anhui has more lakes. Permanent surface water with an inundation frequency of above 75 % covered approximately 4341 km2, accounting for 32.03 % of the total water, while seasonal water with an inundation frequency between 5 % and 75 % covered about 6661 km2, accounting for 49.15 % of the total water, others were considered temporary surface water. By comparing our results with the global annual surface water released by the Joint Research Centre (JRC), we found that our study performed better in extracting lakes and rivers in terms of completeness, but the extraction results for aquaculture areas were slightly less than the JRC dataset. Overall, the long-term surface water dataset established in this study can effectively supplement the existing datasets and provide important references for regional water resource investigation, management, as well as flood monitoring.

Xylocarpin H, a limonoid from the Xylocarpin granatum, exhibits significant biological activities, including antioxidant, antiviral, analgesic, hypnotic, antimalarial, and antidepressant effects, demonstrating considerable potential for drug development. However, few studies have been reported to identify and classify active metabolites responsible for such excellent biological activities. In this study, we utilized ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC–Q–TOF–MS/MS) coupled with multiple data postprocessing techniques to rapidly identify in vivo and in vitro metabolites of xylocarpin H. Consequently, a total of 32 metabolites (23 in phase I and 9 in phase II) of xylocarpin H were detected both in rat feces, urine, bile, blood, intestinal flora, and rat and human liver microsomes. The metabolic pathways of xylocarpin H mainly involve hydrolysis, oxidation, reduction, addition, glucose conjugation, glucuronide conjugation, and sulfate conjugation. The metabolite M15 of xylocarpin H was synthesized by ester hydrolysis and its structure was determined by nuclear magnetic resonance spectroscopy. This study elucidates the metabolic pathways of xylocarpin H and provides insights into the origin of its pharmacological activity.

Prior research on vegetation indices (VIs) to estimate species diversity in forest and grassland ecosystems has shown limitations when applied to wetland ecosystems due to their complex structure. Consequently, the predictive capacity of various VIs for wetland plant species diversity and their susceptibility to image noise remain largely unknown. To address these gaps, we utilized high-resolution multispectral images from Unmanned Aerial Vehicles (UAV) and field survey data in marsh wetlands. Various VIs and species diversity indices were computed, and univariate and multiple linear regression models were employed to assess predictive ability of the mean, standard deviation, and coefficient of variation of VIs for wetland plant species diversity. Results revealed that MTCI and NDREI exhibited the highest predictive ability for plant species diversity both before and after masking image noise. While most VIs generally improved in predictive ability after masking image noise, their susceptibility to it varied. MTCI, NDREI, SAVI, MSAVI, and MSAVI2 were less affected by image noise, with minimal changes in predictive ability before and after masking image noise. Conversely, CTVI, NDVI, and other VIs showed high susceptibility to image noise, with significant improvement in predictive ability after masking. ANOVA results indicated that integrating the mean and standard deviation of VIs into models significantly enhanced estimates of species diversity, highlighting their complementarity in predicting species diversity. These findings provide valuable insights into the predictive ability of different VIs for wetland plant species diversity, guiding selection of optimal VIs for predicting plant species diversity at broader scales in the future.

High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.

Hypoxia-induced apoptosis of bone marrow mesenchymal stem cells (BMSCs) limits the efficacy of their transplantation for steroid-induced osteonecrosis of the femoral head (SONFH). As apoptosis and RNA methylation are closely related, exploring the role and mechanism of RNA methylation in hypoxic apoptosis of BMSCs is expected to identify new targets for transplantation of BMSCs for SONFH and enhance transplantation efficacy. We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA-seq on a hypoxia-induced apoptosis BMSC model and found that the RNA methyltransferase-like 3 (METTL3) is involved in hypoxia-induced BMSC apoptosis. The expression of METTL3 was downregulated in BMSCs after hypoxia and in BMSCs implanted in osteonecrosis areas. Knockdown of METLL3 under normoxic conditions promoted apoptosis of BMSCs. In contrast, overexpression of METTL3 promoted the survival of BMSCs under hypoxic conditions, and overexpression of METTL3 promoted the survival of BMSCs in the osteonecrosis area and the repair of the osteonecrosis area. Regarding the mechanism, the m6A levels of the mRNAs of anti-apoptotic genes Bcl-2, Mcl-1, and BIRC5 were significantly increased upon the overexpression of METTL3 under hypoxic conditions, which promoted the binding of Bcl-2, Mcl-1, and BIRC5 mRNAs to IGF2BP2, enhanced the mRNA stability, and increased the protein expression of the three anti-apoptotic genes. In conclusion, overexpression of METTL3 promoted m6A modification of mRNAs of Bcl-2, Mcl-1, and BIRC5, promoted the binding of IGF2BP2 to the above-mentioned mRNAs, enhanced mRNA stability, inhibited hypoxia-induced BMSC apoptosis, and promoted repair of SONFH, thereby providing novel targets for transplantation of BMSCs for SONFH.

Magnesium-based composites are a focal point in biomaterials research. However, the rapid degradation rate of magnesium alloys does not align with the healing time of bone tissue. Additionally, the host reaction caused by magnesium implantation hampers its full osteogenic potential. To maintain an appropriate microenvironment, it is important to enhance both corrosion resistance and osteogenic activity of the magnesium matrix. In this study, a composite scaffold composed of mineralized collagen and magnesium alloy was utilized to investigate the regulatory effect of mineralized collagen on mouse macrophages and evaluate its impact on mouse bone marrow mesenchymal stem cells in terms of osteogenesis, immune response, and macrophage-induced osteogenic differentiation. This experiment examined the biocompatibility of mouse bone marrow mesenchymal stem cells and macrophage-induced osteogenic differentiation in vitro, and examined the expression levels of relevant pathways proteins. Magnesium calcium alloys/mineralized collagen exhibited extensive spreading, facilitated by broad and abundant pseudopodia that firmly adhered them to the material surface and promoted growth and pseudopodia formation. The findings revealed that magnesium calcium alloy/mineralized collagen scaffold materials induced osteogenic differentiation mainly through M2 polarization of macrophages. This effect was mainly mediated by promoting the integrin α2β1-FAK-ERK1/2 signaling pathways and inhibiting the RANK signaling pathways.

Alginate is the most abundant polysaccharide compound in brown algae, which is widely used in various fields. At present, the determination of the content of alginate is mostly carried out using sulfuric acid and trifluoroacetic acid hydrolysis followed by the determination of the content, but the results are not satisfactory, and there are problems such as low hydrolysis degree and low recovery rate. Therefore, in this study, based on the optimization of high performance liquid chromatographic conditions for pre-column derivatization of 1-phenyl-3-methyl-5-pyrazolone (PMP), the hydrolysis effects of sulfuric acid, trifluoroacetic acid (TFA), oxalic acid, and formic acid were compared and the hydrolysis conditions were optimized. The results showed that formic acid was the best hydrolyzing acid. The optimal hydrolysis conditions were 95 % formic acid at 110 °C for 10 h. The hydrolysis effect was stable, with high recovery and low destruction of monosaccharides, which made it possible to introduce formic acid into the subsequent polysaccharide hydrolysis. The pre-column derivatization high performance liquid chromatography method established in this study was accurate and reliable, and the hydrolysis acid with better effect was screened, which provided a theoretical basis for the subsequent determination of alginate content.

Summary: Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients’ survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. Methods: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. Findings: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. Interpretation: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. Funding: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Summary: Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs. Here, we demonstrated in vivo sufficient visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using the pair of a codon-optimized Akaluc and AkaLumine. We engineered the codon-optimized Akaluc gene possessing the similar GC ratio of SARS-CoV-2. Using the SARS-CoV-2 recombinants carrying the codon-optimized Akaluc, we visualized in vivo infection of respiratory organs, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of antivirals by monitoring changes in Akaluc signals. Overall, we offer an effective technology for monitoring viral dynamics in live animals.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a “multi-omics” platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.