The impact of digital transformation of commercial banks on household income: Evidence from China.

Scholars have focused on the digital transformation of commercial banks, yet there remains a lack of systematic and integrative research at the micro-level of household finance. This article uses data from the China Household Finance Survey (CHFS) and the Digital Transformation Index of Chinese Commercial Banks from Peking University. It employs empirical methods such as mechanism analysis and heterogeneity analysis to explore the impact of the digital transformation of commercial banks on household income. The findings indicate that the digital transformation of commercial banks significantly enhances household income. Second, increasing credit availability, fostering the development of digital inclusive finance, enhancing entrepreneurial possibilities, and increasing the purchase of wealth management products are key pathways through which digital transformation affects household income. Third, heterogeneity analysis reveals that the positive effects of digital transformation on household income are more pronounced in the central and western regions, areas with lower financial industry competition, regions with underdeveloped inclusive finance, rural areas, and among low-income families. This study highlights the significant role that the digital transformation of commercial banks plays in enhancing the welfare of the resident sector.

Low-carbon Treatment and Remediation of Oil Sludge in Mid-to-high Latitude Regions: A Coupled Approach of Freeze-Thaw and Supercritical CO2 Extraction.

The oil sludge produced while extracting large oil and gas fields in the middle and high latitude regions has caused serious pollution to the surrounding soil. The key to solving this problem in the future is to unify the remediation of soil and the treatment of oil sludge. This study uses supercritical carbon dioxide(scCO2) technology to construct a low-carbon method, providing a new approach to achieve this goal. The study determines the optimal extraction conditions for black calcareous soil with 15% oil content to be 55 °C, 25 MPa, and 90 min through single factor and response surface experiments. Experiments on the scCO2 extraction coupled with freeze-thaw cycles show that oil sludge with a water content of 10% can improve the extraction efficiency of scCO2 by about 2.69% after less than five freeze-thaw cycles. The study also compares the extraction efficiency of the four soils, with a difference of 6.03% observed under the same conditions. Additionally, we analyze the impact of the extraction process on changes in the properties of the oil and soil in the oil sludge. Comprehensive tests, including scanning electron microscope (SEM), nutrient detection, X-ray powder diffractometer (XRD), fourier transform infrared spectroscopy (FTIR), and Gas Chromatography (GC), have been conducted. Results show that standalone scCO2 extraction can remove up to 98.2% of petroleum hydrocarbons from the oil sludge, while simultaneously causing small changes to the soil microstructure and the crystal structure of the oil sludge. Furthermore, this process does not lead to a significant depletion of key nutrients or the generation of new pollutants.

Fibroblast activation protein inhibitor positron emission tomography imaging in muscles of patients with idiopathic inflammatory myopathy.

OBJECTIVES: Mesenchymal stromal cells in muscles participate in regeneration following muscle injury. This study explored the potential of [18F]fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography (PET) targeting mesenchymal stromal cells to evaluate disease activity of idiopathic inflammatory myopathy (IIM). METHODS: Patients with IIM (n = 26) were prospectively included and underwent [18F]FAPI-42 PET/CT and whole-body MRI between January 2023 and July 2023. Patients with malignancies were retrospectively included in the control group and only underwent [18F]FAPI-42 PET/CT (n = 28). [18F]FAPI-42 PET/CT images were evaluated using for avid-FAPI uptake and the target-to-background ratio (TBR). Whole-body MRI was evaluated for oedema, fatty infiltration, and atrophy in 42 muscles in the IIM group. The global FAPI- and MRI-derived parameters were calculated for each. PATIENT: . Clinical assessment of disease activity and muscle strength were collected. RESULTS: Patients with IIM had significantly higher global FAPI-avid muscle ratios (0.68 [interquartile range (IQR): 0.45, 0.79] vs 0.06 [IQR: 0, 0.11], p< 0.001) and global muscle TBR (2.26 [IQR: 1.71, 2.75] vs 1.23 [IQR: 1.02, 1.52], p< 0.001) compared with controls. In the IIM group, the median TBR was higher in muscles with oedema than in those without (2.44 [IQR: 1.46, 3.27] vs 1.31 [IQR: 0.95, 1.99], p< 0.001). Global FAPI-avid muscle ratios significantly correlated with global oedema score (r = 0.833), muscle strength (r=-0.649), serum creatine kinase (r = 0.456), and disease activity index (r = 0.495-0.621). CONCLUSION: Increased [18F]FAPI-42 uptake was associated with muscle oedema in IIM. FAPI-derived parameters correlated with IIM disease activity. [18F]FAPI-42 is a promising PET tracer for evaluating IIM disease activity.

The relationship between air pollution and the occurrence of hypertensive disorders of pregnancy: Evidence from a study in Wuhan, China.

Ambient air pollution has been reported to be a risk factor for hypertensive disorders of pregnancy (HDP). Past studies have reported supportive evidence, but evidence from China is scarce and does not integrate the different periods of the pregnancy course. In this study, 1945 pregnant women with HDP and healthy pregnancies between 2016 and 2022 from the Renmin Hospital of Wuhan University registry network database were analysed. The geographic information, biological information and demographic information of the case were fused in the analysis. Machine learning methods were used to obtain the weight of the variable. Then, we used the generalized linear mixed model to evaluate the relationship between increased exposure to each pollutant at different periods of HDP and examined it in different groups. The results showed that SO2 had the predominate impact (12.65 %) on HDP compared with other air pollutants. SO2 exposure was associated with an increased risk of HDP. Increased unit SO2 concentrations were accompanied by an increased risk of HDP (OR = 1.33, 95 % CI: 1.13, 1.566), and the susceptible window for this effect was mainly in the first trimester (OR = 1.242, 95 % CI: 1.092, 1.412). In addition, SO2 exposure was associated with an increased risk of HDP in urban maternity (OR = 1.356, 95 % CI: 1.112, 1.653), obese maternity (OR = 3.58, 95 % CI: 1.608, 7.971), no higher education maternity (OR = 1.348, 95 % CI: 1.065, 1.706), nonzero delivery maternity (OR = 1.981, 95 % CI: 1.439, 2.725), maternal with first time maternity (OR = 1.247, 95 % CI: 1.007, 1.544) and other groups. In summary, SO2 exposure in early pregnancy is one of the risk factors for HDP, and the increased risk of HDP due to increased SO2 exposure may be more pronounced in obese, urban, low-education, and nonzero delivery populations.

The Synthesis and Properties of Spirophenanthrene.

Motivated by the success of 9,9'-spirobifluorene (SBF) in optoelectronic materials, we synthesized a novel spiro compound, spirophenanthrene (SP). Incorporating a phenanthrene unit as the core, we aimed to leverage the π-conjugation of SPs to surpass the limitations of SBF. Experimental and theoretical studies revealed significant advantages over SBF, including red-shifted wavelengths, tunable LUMO energy levels, and enhanced thermal stability. These advantages suggest the potential of SPs as versatile building blocks for diverse optoelectronic devices.

Construction of highly active and stable recombinant nattokinase by engineered bacteria and computational design.

Nattokinase (NK) is an enzyme that has been recognized as a new potential thrombolytic drug due to its strong thrombolytic activity. However, it is difficult to maintain the enzyme activity of NK during high temperature environment of industrial production. In this study, we constructed six NK mutants with potential for higher thermostability using a rational protein engineering strategy integrating free energy-based methods and molecular dynamics (MD) simulation. Then, wild-type NK and NK mutants were expressed in Escherichia coli (E. coli), and their thermostability and thrombolytic activity were tested. The results showed that, compared with wild-type NK, the mutants Y256P, Q206L and E156F all had improved thermostability. The optimal mutant Y256P showed a higher melting temperature (Tm) of 77.4 °C, an increase of 4 °C in maximum heat-resistant temperature and an increase of 51.8 % in activity at 37 °C compared with wild-type NK. Moreover, we also explored the mechanism of the increased thermostability of these mutants by analysing the MD trajectories under different simulation temperatures.

Family management styles for children with asthma: A latent profile analysis.

AIM: To identify the latent profiles and predictors of family management styles for children with asthma. DESIGN: This is a secondary data analysis. The demographic data of 506 primary caregivers of children with asthma and their scores of the Family Management Scale in a cross-sectional study were used. Latent profile analysis and multiple logistic regression analyses were employed. RESULTS: Three family management styles were identified: Thriving (Profile 1), Accommodating (Profile 2), and Enduring (Profile 3) Family Management Style. The child's age, gender, mother's education level, family structure, influence of illness on parents' work and family life, whether they had follow-up plans and whether their parents had read disease and health knowledge pamphlets were found to be the predictors of different styles. CONCLUSION: Three distinct family management styles exist for children with asthma. Future interventions designed to enhance family management for children with asthma should be based on their demographic characteristics and family management styles. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The precise classification of family management styles in this study can serve as a guide to form multi-disciplinary teams of physicians and nurses to provide individualized care and conduct in-depth research to explore the mechanisms of biomedicine and the social psychology of asthma in the future. IMPACT: This paper aims to identify the latent profiles and predictors of family management styles of children with asthma. Thriving, accommodating, and enduring family management styles were identified in this paper. Child's characteristics, family and organizational factors were the predictors of different family management styles. Findings of this paper provide guidance for physicians and nurses to offer individualized care and conduct in-depth research to explore the mechanisms of biomedicine and the social psychology of asthma in the future. REPORTING METHOD: The article was reported according to the STROBE Checklist. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Chinese medicine Linggui Zhugan formula protects against diabetic kidney disease in close association with inhibition of proteinase 3-mediated podocyte apoptosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY: This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND METHODS: LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage. RESULTS: Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis. CONCLUSION: Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.

Association between dietary magnesium intake and pelvic inflammatory disease in US women: a cross-sectional study of NHANES.

Background: Pelvic inflammatory disease (PID) is a common gynecological condition associated with significant morbidity and healthcare costs. Emerging evidence suggests that dietary factors, such as magnesium intake, may play a role in PID risk. However, the relationship between dietary magnesium intake and PID risk remains uncertain. This cross-sectional study aimed to investigate the association between dietary magnesium intake and the risk of PID. Methods: This cross-sectional study included data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018. Weighted multivariable logistic regression was used to examine the association between dietary magnesium intake and PID. Restricted cubic spline (RCS) analysis was performed to assess the linear and non-linear associations. Subgroup analyses were performed based on baseline characteristics. Results: A total of 3,034 women aged 20-59 were included in the study. Magnesium intake exhibited a significant association with lower PID risk in weighted multivariable logistic regression. Adjusted odds ratios (ORs) for dietary magnesium intake in quartiles Q2 (133.12-214.93 mg/day), Q3 (214.93-287.19 mg/day), and Q4 (above 287.19 mg/day) compared to Q1 (below 133.12 mg/day) were 0.48 (95% CI: 0.28-0.82), 0.64 (95% CI: 0.32-1.27), and 0.40 (95% CI: 0.18-0.88), respectively. Stratified analyses showed that significant association between dietary magnesium intake and PID in older subgroup but not in younger subgroup. Additionally, RCS analyses consistently revealed a linear negative correlation between dietary magnesium intake and PID risk. Conclusion: This study reveals a significant negative correlation between dietary magnesium intake and risk of PID, particularly among older individuals. These findings underscore the importance of dietary factors in gynecological health and highlight the potential role of magnesium supplementation in PID prevention strategies.

An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.

PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. METHODS: To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in GC. RESULTS: Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. CONCLUSION: PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.

Enzyme-Responsive Micelles with High Drug-Loading Capacity for Antitumor Therapy.

To overcome the poor targeting of conventional chemotherapeutic drugs and the defects of low drug-loading capacity of conventional drug delivery systems, novel drug delivery systems with high drug-loading capacity are developed. Herein, the high drug-loaded mPEG79-GFLGDDD-DOX copolymer is first synthesized via an amide reaction, which can bond multiplex DOX. After PEGylation, the drug can resist the adsorption of proteins in the plasma in blood circulation, avoid being rapidly cleared out of the body, and prolong the circulation time of the drug in the blood, which is conducive to the enrichment of micelles in tumor tissues through the EPR effect. In tumor tissues, the peptide Glycine- Phenylalanine- Leucine- Glycine (GFLG) is recognized and sheared by overexpressed cathepsin B, which stripped the outer layer of methoxy polyethylene glycol (mPEG) and made it more readily available for uptake by tumor cells. After entering the tumor cells, the bonded DOX and the physically encapsulated DOX in the micelles played a synergistic role, realizing the killing of tumor cells, thus effectively enhancing the therapeutic effect on tumors. The findings in this work suggest that a high drug-loading drug delivery system has great potential in the clinical treatment of tumors.

Synthesis and Antiallergic Activity of Dicoumarin Derivatives.

Allergies are one of the diseases whose incidence rates have increased in recent years due to the greenhouse effect and extreme climate change. Therefore, the development of new antiallergic drugs has attracted the interest of researchers in chemistry and pharmacy fields. Dicoumarin is a coumarin derivative with various biological activities, but its antiallergic activity has not been evaluated. In this study, 14 different dicoumarin derivatives were synthesized by diethylamine-catalyzed condensation reactions of 4-hydroxycoumarin with 14 different aldehydes, and they were identified on the basis of their spectral data. The dicoumarin derivatives were subjected to studies on the degranulation of rat basophilic leukemia cells (RBL-2H3 cells) and mouse bone-marrow-derived mast cells (mBMMCs), and some of them showed good inhibitory effects on the degranulation of the two types of mast cells, demonstrating their good antiallergic activity. This study presents a new method of developing new antiallergic drugs.

ConvFormer-KDE: A Long-Term Point-Interval Prediction Framework for PM2.5 Based on Multi-Source Spatial and Temporal Data.

Accurate long-term PM2.5 prediction is crucial for environmental management and public health. However, previous studies have mainly focused on short-term air quality point predictions, neglecting the importance of accurately predicting the long-term trends of PM2.5 and studying the uncertainty of PM2.5 concentration changes. The traditional approaches have limitations in capturing nonlinear relationships and complex dynamic patterns in time series, and they often overlook the credibility of prediction results in practical applications. Therefore, there is still much room for improvement in long-term prediction of PM2.5. This study proposes a novel long-term point and interval prediction framework for urban air quality based on multi-source spatial and temporal data, which further quantifies the uncertainty and volatility of the prediction based on the accurate PM2.5 point prediction. In this model, firstly, multi-source datasets from multiple monitoring stations are preprocessed. Subsequently, spatial clustering of stations based on POI data is performed to filter out strongly correlated stations, and feature selection is performed to eliminate redundant features. In this paper, the ConvFormer-KDE model is presented, whereby local patterns and short-term dependencies among multivariate variables are mined through a convolutional neural network (CNN), long-term dependencies among time-series data are extracted using the Transformer model, and a direct multi-output strategy is employed to realize the long-term point prediction of PM2.5 concentration. KDE is utilized to derive prediction intervals for PM2.5 concentration at confidence levels of 85%, 90%, and 95%, respectively, reflecting the uncertainty inherent in long-term trends of PM2.5. The performance of ConvFormer-KDE was compared with a list of advanced models. Experimental results showed that ConvFormer-KDE outperformed baseline models in long-term point- and interval-prediction tasks for PM2.5. The ConvFormer-KDE can provide a valuable early warning basis for future PM2.5 changes from the aspects of point and interval prediction.

Self-Referenced Au Nanoparticles-Coated Glass Wafers for In Situ SERS Monitoring of Cell Secretion.

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for discrimination of bimolecules in complex systems. However, its practical applications face challenges such as complicated manufacturing procedures and limited scalability of SERS substrates, as well as poor reproducibility during detection which compromises the reliability of SERS-based analysis. In this study, we developed a convenient method for simultaneous fabrication of massive SERS substrates with an internal standard to eliminate the substrate-to-substrate differences. We first synthesized Au@CN@Au nanoparticles (NPs) which contain embedded internal standard molecules with a single characteristic peak in the Raman-silent region, and then deposited the NPs on 6 mm glass wafers in a 96-well plate simply by centrifugation for 3 min. The one-time obtained 96 SERS substrates have excellent intrasubstrate uniformity and intersubstrate repeatability for SERS detection by using the internal standard (relative standard deviation = 10.47%), and were able to detect both charged and neutral molecules (crystal violet and triphenylphosphine) at a concentration of 10-9 M. Importantly, cells can be directly cultured on glass wafers in the 96-well plate, enabling real time monitoring of the secretes and metabolism change in response to external stimulation. We found that the release of nucleic acids, amino acids and lipids by MDA-MB-231 cells significantly increased under hypoxic conditions. Overall, our approach enables fast and large-scale production of Au@CN@Au NPs-coated glass wafers as SERS substrates, which are homogeneous and highly sensitive for monitoring trace changes of biomolecules.

LATS1 inhibitor and zinc supplement synergistically ameliorates contrast-induced acute kidney injury: Induction of Metallothionein-1 and suppression of tubular ferroptosis.

Contrast-induced acute kidney injury (CI-AKI) is a prevalent cause of renal dysfunction among hospitalized patients, yet the precise pathogenesis and effective therapeutic strategies remain elusive. In this study, we investigated the role of tubular ferroptosis in both experimental CI-AKI models and in primary tubular epithelial cells (PTECs) treated with ioversol. Using whole exome sequencing, we identified metallothioneins (MTs) as being among the most significantly downregulated genes following ioversol exposure. Our findings reveal that overexpression of Mt1 mitigates, whereas suppression of Mt-1 exacerbates, ioversol-induced tubular ferroptosis. Interestingly, the level of MTF1 (metal regulatory transcription factor 1), a principal regulator of Mt1, was found to increase in response to ioversol treatment. We further elucidated that ioversol activates LATS1 (Large tumor suppressor homolog 1), a kinase that promotes the phosphorylation and nuclear translocation of MTF1, thereby inhibiting its transcriptional activity for Mt1. Both genetic and pharmacological inhibition of LATS1 reversed the ioversol-induced suppression of Mt-1. From a therapeutic perspective, the LATS1 inhibitor TDI-011536, in combination with zinc acetate, was administered to a rodent model of CI-AKI. Our data indicate that this combination synergistically upregulates Mt1 expression and provides protection against contrast media-induced tubular ferroptosis. In summary, our study demonstrates that the reduction of Mt-1 contributes to tubular ferroptosis associated with CI-AKI. We show that contrast media activate LATS1, which in turn suppresses the transcriptional activity of MTF1 for Mt1. Herein, the combination of zinc acetate and a LATS1 inhibitor emerges as a potential therapeutic approach for the treatment of CI-AKI.

miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2.

MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.

Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587.

Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.

Characterization and structural identification of a novel alginate-specific carbohydrate-binding module (CBM): The founding member of a new CBM family.

Alginate is a commercially important polysaccharide widely distributed in brown algae. Carbohydrate-binding modules (CBMs), a class of commonly used polysaccharide-binding proteins, have greatly facilitated the investigations of polysaccharides. Few alginate-binding CBMs have been hitherto reported and structurally characterized. Herein, an unknown domain from a potential PL6 family alginate lyase in the marine bacterium Vibrio breoganii was discovered and recombinantly expressed. The obtained protein, designated VbCBM106, displayed the favorable specificity to alginate. The unique sequence and well-defined function of VbCBM106 reveal a new CBM family (CBM106). Moreover, the structure of VbCBM106 was determined at a 1.5 Å resolution by the X-ray crystallography, which shows a typical ß-sandwich fold comprised of two antiparallel ß-sheets. Site-directed mutagenesis assays confirmed that positively charged polar residues are crucial for the ligand binding of VbCBM106. The discovery of VbCBM106 enriches the toolbox of alginate-binding proteins, and the elucidation of critical residues would guide the future practical applications of VbCBM106.

Identification of spatial protection and restoration priorities for ecological security pattern in a rapidly urbanized region: A case study in the Chengdu-Chongqing economic Circle, China.

The continuous expansion of modern cities not only leads to ecological degradation but also seriously threatens regional ecological security and sustainable development. The construction of ecological security patterns (ESPs) has emerged as a significant approach to alleviate or even solve the conflict between regional development and ecological protection. The Chengdu-Chongqing Economic Circle (CCEC) represents the core area of regional economic development strategy in western China, characterized by rapid economic growth from 2000 to 2020. This study integrates assessments of ecosystem services importance, eco-environmental sensitivity and landscape connectivity; uses circuit theory and hydrological analysis to establish a research framework for the spatiotemporal evolution of regional ESP; and develops an optimized ESP combined with the Major Function Oriented Zone. The results indicate that urban expansion significantly impacted the ESP of the CCEC between 2000 and 2020. The fragmentation and merging of ecological sources occurred simultaneously, the number of patches reduced by 28.13% from 64 to 46. The early ecological security network was compromised, leading to the disappearance or elongation of some ecological corridors. The number of ecological corridors decreased by 36.03% from 136 to 87; the total length was reduced by 29.92% from 7500.57 km to 5256.28 km. Urgent optimization of the ESP is needed, reducing the number of key ecological protection areas by 50% from 106 to 53 while increasing priority restoration areas by 13.51% from 37 to 42. The study also reveals the insufficiency of the current Major Function Oriented Zone in protecting linear corridors, necessitating focused attention on the protection and restoration of ecological sources and surrounding corridors in important development zones. Additionally, a spatial optimization strategy of "one shelter, two cores, and three regions" is proposed to enhance regional ecosystem stability and connectivity. The aim was to strike a balance between ecological protection and food security by recommending an ecological corridor width range of 30∼100 m. These research findings offer scientific guidance for ecological space protection and restoration in the CCEC, contributing to the enhancement of both scientific and rational ecological planning in rapidly urbanizing areas.