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Background: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. Methods: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. Results: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. Conclusions: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Background: No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC. Methods: Fifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity. Results: In patients with advanced ESCC, the anlotinib plus camrelizumab group (N = 32) exhibited longer PFS (8.00 vs. 4.53 months, P

The delineation of urban development boundaries (UDBs) is an essential part of spatial planning and a powerful tool for implementing spatial governance. With the central city of Nanjing as an example, we used various models, including the logistic regression analysis model, InVEST model, and cellular automaton (CA) model, to evaluate the ecological importance, simulate the spatial expansion of construction land, and delineate the UDBs of various urban spatial units under ecological constraints, and determine the eco-environmental effects of the obtained UDBs. The results revealed that the important ecological lands, which were mostly woodlands, covered 422.05 km2 and acted as the ecological bottom line for regional sustainable development. The simulated UDBs under ecological constraints considered the dual demands of urban spatial expansion and a high-quality eco-environment; they effectively prevented urban expansion from occupying important ecological lands and destroying regional eco-environmental quality. The obtained UDBs were highly consistent with the proposed urban layout of local governments, and our simulated results of the UDBs could provide differentiated development orientations from the perspective of land use protection and development. Finally, we noted that urban expansion is dynamic, complex, and systematic and is also affected by the interaction of multiple factors, and the constraint of ecological importance should be emphasized to coordinate the relationship between land development and ecological protection.

The empirical relationships between tensile strength, mode I and mode II fracture toughness obtained by previous studies have the problem of a small amount of data for fitting, and more data are needed for further study. There is a discrepancy between the theoretical prediction and the experimental results of the relationship between mode II and mode I fracture toughness. Because of this, a review is conducted to determine the relationships among tensile strength, mode I fracture toughness, and mode II fracture toughness from the data gathered from the available literature. The results indicate that the mode I and mode II fracture toughness have linear relationships with tensile strength with the linear coefficient of 0.141 and 0.219, respectively. The linear coefficient between mode II and mode I fracture toughness is 2.389, indicating that the classical mixed mode criteria are mistaken the empirical relationship between mode II and mode I fracture toughness. The microcracking mechanism and failure model are quantified and compared in detail among tensile test, mode I and mode II fracture toughness tests based on moment tensor. It found that the nature of the source can be related to each other, which gives some light on the reason for the existence of certain relationships between these macroscopic parameters from a microcracking perspective.

Summary: Although diverse microorganisms can remove ammonium and nitrate simultaneously, their metabolic mechanisms are not well understood. Paracoccus denitrificans R-1 showed the maximal NH4+ removal rate 9.94 mg L−1·h−1 and 2.91 mg L−1·h−1 under aerobic and anaerobic conditions, respectively. Analysis of the nitrogen balance calculation and isotope tracing experiment indicated that NH4+ was consumed through assimilation. The maximal NO3− removal rate of strain R-1 was 18.05 and 19.76 mg L−1·h−1 under aerobic and anaerobic conditions, respectively. The stoichiometric consumption ratio of acetate to nitrate was 0.902 and NO3− was reduced to N2 for strain R-1 through 15NO3− isotopic tracing experiment, which indicated a respiratory process coupled with the oxidation of electron donors. Genomic analysis showed that strain R-1 contained genes for ammonium assimilation and denitrification, which effectively promoted each other. These findings provide insights into microbial nitrogen transformation and facilitate the simultaneous removal of NH4+ and NO3− in a single reactor.

Achieving spatiotemporal balance between carbon emissions and sinks at multiple spatial scales is vital for addressing climate change globally. The investigation of carbon budget variation and carbon balance zoning at the intra-city scale, however, has not received much scholarly attention. By integrating firm-level big data with other datasets, this paper aims to simulate high-resolution carbon emissions and sinks and to reveal the spatiotemporal variation of carbon budgets within Nanjing, one of metropolises in eastern China, between 2010 and 2019. We then formulated a carbon balance zoning scheme for 111 township-level regions of Nanjing based on the evaluation indicator system and clustering methods. Empirical results imply that the spatial pattern of carbon emissions has experienced a reshaping tendency from core-periphery to polycentric structure, while the scale and geography of territorial ecosystem carbon sinks remained stabilize during the past decade. There existed a spatial agglomeration effect in functional zones oriented by intra-city carbon balance of Nanjing. These are tied to determinants such as urban expansion, population redistribution, industrial restructuring, as well as regulations on energy use, natural resource supervision and ecosystem protection. The newly built urban sub-centers and new-towns in Nanjing were spatially overlapping with regions where significant changes in carbon budgets occurred. Our findings suggest that the current system of territorial governance should be reformed to support the adoption of major function and carbon balance zoning oriented by carbon peaking and neutrality at finer geographical scales in China.

Background: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. Methods: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). Results: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. Conclusion: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients’ prognoses.

Rapidly expanding studies investigate the effects of e-commerce on company operations in the retail market. However, the interaction between agri-food e-commerce (AEC) and the traditional agri-food wholesale industry (AWI) has not received enough attention in the existing literature. Based on the provincial panel data from 2013 to 2020 in China, this paper examines the effect of AEC on AWI, comprising three dimensions: digitalization (DIGITAL), agri-food e-commerce infrastructure and supporting services (AECI), and agri-food e-commerce economy (AECE). First, AWI and AEC are measured using an entropy-based combination of indicators. The results indicate that for China as a whole, AWI has remained practically unchanged, whereas AEC exhibits a significant rising trend. Second, the findings of the fixed-effect regression reveal that DIGITAL and AECE tend to raise AWI, whereas AECI negatively affects AWI. Third, threshold regression results indicate that AECI tends to diminish AWI with three-stage inhibitory intensity, which manifests as a first increase and then a drop in the inhibition degree. These results suggest that with the introduction of e-commerce for agricultural product circulation, digital development will have catfish effects that tend to stimulate the vitality of the conventional wholesale industry and promote technical progress. Furthermore, the traditional wholesale industry benefits financially from e-commerce even while it diverts part of the traditional wholesale circulation for agricultural products.

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

Objective: To investigate the effect of a 16-week Tai Chi practice on strength, tactile sensation, kinesthesia, and static postural control among older adults of different age groups. Methods: This is a quasi-experimental study. Thirteen participants aged 60–69 years (60–69yr), 11 aged 70–79 years (70–79yr), and 13 aged 80–89 years (80–89yr) completed 16 weeks of 24-form Tai Chi practice. Their ankle and hip peak torque, tactile sensation, ankle and knee kinesthesia, and the root mean square of the center of pressure (Cop-RMS) were measured before (week 0) and after (week 17) practice. Results: 80–89yr showed less ankle plantar/dorsiflexion and hip abduction peak torques (p = 0.003, p

A systematic analytical approach has been developed to comprehensively characterize the creep damage material properties of coatings on thin-layer substrates. This involves conducting creep tests using a compound, two-material, miniaturized thin plate specimen (MTPS) with an inverse approach. For demonstration, independent creep tests were performed on miniature specimens of the substrate (P91 steel) and the coating (CoNiCrAlY) at 650 °C, as well as on compound substrate-coating specimens. The reference stress method, coupled with finite element analysis, was utilized to obtain conversion parameters for strain data from the miniature specimen tests. Analytical solutions for the Kachanov creep damage model specific to the two-material substrate-coating system were adopted for inverse optimization. The MTPS testing method and the associated inverse approach have proven effective in accurately determining the complete three-stage creep constants within the coating-substrate system. Results obtained for the P91–CoNiCrAlY coated system have shown a clear demonstration of the accuracy and capability of the method in identifying the full sets of uniaxial creep damage properties, i.e. A, n, m, B, χ, and φ, provided the feasible experimental data are available.

Due to sanctions, more Chinese high-tech SMEs are turning to rent AI computing power through cloud service providers. Therefore, it is necessary to give a variety of suggestions for China's high-tech SMEs to better develop AI applications through computing power leasing. Because traditional theories are difficult to explain this new technology adoption behavior, this research combines and extends TTF and UTAUT2 theories to take an empirical research. A total of 387 questionnaires were received, of which incomplete questionnaires and invalid questionnaires were issued, leaving 281 valid questionnaires. The results indicate that SME innovativeness, perceived risk, performance expectancy, price value and task technology fit are all significantly related to usage, whereas task technology fit moderates the other relationships significantly. Results give a variety of suggestions for China's high-tech SMEs to better develop AI applications through computing power leasing in the context of sanctions. This study not only suggests ways to increase the competitiveness of SMEs by optimizing leasing services but also give directions in investors' investment decisions. The findings are also applicable to the large-scale application of China's domestic AI chips in computing power leasing scenarios in the future.

Summary: Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/β-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

Objective: Osteosarcoma (OS) is the most common primary bone sarcoma with a high propensity for local invasion and metastasis. Although the antitumor effect of apatinib has been well confirmed in advanced OS, the synergistic effect of apatinib and immunotherapies has not yet been elucidated. Methods: In this study, we established tumour-bearing mice and observed tumour size with low and high doses of apatinib treatments. The expression of 17 cytokines, including vascular endothelial growth factor (VEGF), was detected by protein microarray analysis. Moreover, we designed apatinib and antigen-specific dendritic cell (DC)-T combination treatment for tumour-bearing mice. Tumour growth was detected by statistical analysis of tumour size and microvessel density (MVD) counting, the protein expression of VEGF by western blotting, the cytokines interleukin 6 (IL-6), IL-17 and interferon-gamma (IFN-γ) by enzyme-linked immunosorbent assay (ELISA), and the numbers of myeloid-derived suppressor cells (MDSCs) and tumour-infiltration macrophages (TAMs) by flow cytometry. Results: The results showed that apatinib efficiently suppressed tumour growth, and high-dose apatinib achieved a stronger effect. The same was true for DC-T immunotherapy. However, their combination treatment revealed a better oncolytic effect. Meanwhile, apatinib or DC-T treatment inhibited the expression of VEGF and the proangiogenic mediators IL-6 and IL-17 but increased IFN-γ production. Combination therapy further reduced/increased these effects. In addition, the combination treatment reduced MDSC but enhanced TAM-M1 ratios in the OS microenvironment. These findings indicated that apatinib and antigen-specific DC-T combination therapy was more efficient in oncolysis by regulating pro-/anti-angiogenic inducers and improving the immune state in the OS microenvironment. Conclusion: This study proved that it was feasible to employ immunotherapy with therapeutic agents in OS treatment, which may provide a new approach in addition to the combination of surgery with chemotherapy in tumour treatment.

Summary: Atmospheric water harvesting has emerged as an efficient strategy for addressing the global challenge of freshwater scarcity. However, the in being energy-consuming water-collecting process has obstructed its practicality. In this work, a soft drain bed, which was composed of hydrophilic cloth and hygroscopic gel, has been demonstrated to capture atmospheric water effectively, followed by converting it into liquid water spontaneously and sustainably, under all-weather humidity conditions. Under the optimal working condition of 30°C with a relative humidity level of 75%, the bed can provide a spontaneous water oozing ability of 1.25 g (liquid water)/hour within the 8 h of working time. More importantly, after 5 working cycles, 80% of the oozing ability can be reserved, suggesting the high potential for practical freshwater supply application. The proposed design strategy is expected to provide new hints for the development of future energy-saving decentralized freshwater supply systems.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100 nm and/or 1 μm) and Cd for 25 days.The results showed that PS at 100 nm caused more severe oxidative damage and cell apoptosis than PS at 1 μm. Combined exposure to PS at both 100 nm and 1 μm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100 nm vs. 1 μm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100 nm PS+1μm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.

Introduction: The development of small molecule modulators rooted the plant resistance mechanism represents a compelling strategy for improving plant resistance and fortifying food security. Systemins induced by wounds can activate a wide range of plant resistance responses, but compounds that regulate the systemin signaling pathway have yet to be found. Objectives: This study aimed to provide a strategy for the development of small molecule modulators based on virtual screening of systemin receptors. Methods: A systemin receptor model was established for virtual screening, leading to the identification of chemical structure with high binding affinity through molecular docking. Subsequently, the synthesized compound underwent evaluation for its potential to enhance plant resistance against viruses through frictional inoculation. The underlying mechanism of the target compound was analyzed using proteomics. Results: Through virtual screening, a promising active compound, F1, was identified and further optimized. Molecular docking showed that they had the ability to bind SR160. Some of the targeted compounds exhibited potential in enhancing plant resistance against Tobacco mosaic virus (TMV) and Cucumber mosaic virus (CMV). Notably, compound F26 showed satisfactory activity against TMV with an EC50 value of 70.6 μg/mL. The analysis of plant response following treatment with F26 indicated that it may reinforce the plant’s defense mechanisms against viruses by augmenting the wound signaling pathway.

Studies have demonstrated that donkey milk (DM) displays anti-tumor activity. In this study, we investigated the role and underlying mechanism of DM in the progression of 4T1 breast tumors in mice. We found that DM significantly reduced tumor volumes and tumor weights in 4T1-treated mice. Simultaneously, DM ameliorated the pathological changes in spleen, liver and lung tissues of 4T1 tumor-bearing mice. WB results showed that DM inducing the expression of Bax and pyroptosis-related proteins, and inhibiting the expression of Bcl-2 in tumors. Besides, DM up-regulation of Th1 cytokines and down-regulation of Th2/Treg cytokines in the tumors and spleen. Moreover, DM significantly decreased the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-STAT5/STAT5, as well as up-regulation the ratio of p-STAT4/STAT4 in tumors and spleen. Our data suggest that DM inhibit the growth of mouse 4T1 tumors by inducing apoptosis and pyroptosis, as well as promoting Th1 cell activation and quelling immunosuppression from Tregs.

The stability of backfill plays a crucial role in the process of mine operation. In this study, author combined indoor experiments, surface fitting, numerical simulation, and theoretical derivation to investigate how the filling times (FTs), cement tailings ratio (CTR), and minimum CTR filling position (MCFP) affect the uniaxial compressive strength (UCS) and fracture evolution behavior of LCB. The findings demonstrate that an augmentation in FTs reduces the UCS of LCB. Moreover, the highest strength ratio resulting from diverse MCFP amounts to 2.25 times. When once filling, backfill sustain damage as a result of cracks penetrating, whereas LCB that are filled multiple times first encounter damage at the layered contact surface, followed by the gradual spread of cracks until penetrate the LCB. Through an interactive regression model, it is evident that FTs, CTR, and MCFP significantly affect the UCS. Additionally, the interaction between CTR and MCFP has a considerable impact on the UCS. Based on numerical simulation, an increase in FTs results in a wider large displacement area generated by the backfill, leading to greater horizontal and vertical displacement. The MCFP has a significant impact on the lateral displacement and maximum stress of the backfill. Theoretical derivation verifies that MCFP at the top or middle layer results in an increase in the UCS, which is consistent with the experimental findings and numerical simulation. This paper elaborates on the mechanical mechanism behind the interaction between CTR and MCFP. These findings can provide a foundation for assessing the durability and stability of LCB in subsequent stages.

Summary: The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

A novel superhard structure of TiB3 is predicted and its phase transitions, mechanical properties and electronic structure up to 200 GPa are studied employing first-principles calculation. We propose a new structure by substituting the highly stable Amm2 structure with excellent mechanical properties in VB3. Enthalpy calculations demonstrate its superior energetic stability compared to the previously predicted C2/m structure via particle swarm optimization. Furthermore, it maintains stability up to 93.8 GPa and transforms into a P2/m structure under further compression. The Amm2 structure stands as a novel superhard phase with a hardness of 51.6 GPa by Chen’s model, surpassing the C2/m structure by 3.2 GPa. This disparity arises from structural distinctions, with the Amm2 structure featuring boron plates consisting of more layers, resulting in stronger B-B interactions. This novel superhard structure stands as the hardest reported Ti-B compound to date, poised to replace conventional superhard material c-BN in cutting tools and wear-resistant coatings.

Background & Aims: Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery, such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement, and cell polarity. In this study, we explore the role of myeloid Cdc42 in HIRI. Methods: Mouse HIRI models were established with 1-hour ischemia followed by 12-hour reperfusion in myeloid Cdc42 knockout (Cdc42mye) and Cdc42flox mice. Myeloid-derived macrophages were traced with RosamTmG fluorescent reporter under LyzCre-mediated excision. The experiments for serum or hepatic enzymic activities, histologic and immunologic analysis, gene expressions, flow cytometry analysis, and cytokine antibody array were performed. Results: Myeloid deletion of Cdc42 significantly alleviated hepatic damages with the reduction of hepatic necrosis and inflammation, and reserved hepatic functions following HIRI in mice. Myeloid Cdc42 deficiency suppressed the infiltration of myeloid macrophages, reduced the secretion of proinflammatory cytokines, restrained M1 polarization, and promoted M2 polarization of myeloid macrophages in livers. In addition, inactivation of Cdc42 promoted M2 polarization via suppressing the phosphorylation of STAT1 and promoting phosphorylation of STAT3 and STAT6 in myeloid macrophages. Furthermore, pretreatment with Cdc42 inhibitor, ML141, also protected mice from hepatic ischemia-reperfusion injury. Conclusions: Inhibition or deletion of myeloid Cdc42 protects liver from HIRI via restraining the infiltration of myeloid macrophages, suppressing proinflammatory response, and promoting M2 polarization in macrophages.

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 μM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

Due to China’s high demand for foreign crude oil, reducing oil storage energy consumption has become the focus of national attention. In this paper, the mathematical model of the heating process of a single-disk floating roof tank is established. The variation law of the external exergy loss, internal exergy dissipation, exergy flow density and exergy transfer coefficient at different positions of the tank in the heating process are calculated and analysed. The obtained results show that the total exergy flow density is positively correlated with the coil temperature, the number of coil pipes and the diameter of the coil pipes. It is positively correlated with the tank level at the initial stage of heating. The exergy effective utilization rate is proposed to evaluate the energy consumption of the coil in the heating process of the storage tank. The obtained results show that the exergy effective utilization rate is negatively correlated with the liquid level and the temperature of the coil and positively correlated with the number and diameter of the coil, When the heating temperature is 100 °C, the maximum exergy effective utilization rate is 38.73 %.

European Union (EU) has long attached importance to innovation strategies, from the Lisbon strategy to the EU 2020 strategy. The evaluation of sustainable innovation efficiency (SIE) of EU countries aids in defining institutional and policy actions to enhance environmentally friendly innovation in the EU, and is essential and appropriate. Through the data envelopment analysis (DEA) approach, this paper measures the SIE in 27 EU countries, from 2000 to 2017, considering industrial waste and total energy consumption. The results show that the sustainable innovation efficiency among countries differs significantly. Only eight countries consistently have an efficient value of 1 during this period. The EU as a whole has a high efficiency value of 0.7403, but there are obvious differences among the five regions. Efficiency values in the north and south are consistently higher than the EU’s average efficiency value. The results also show that undesirable outputs lead to the reduction of innovation efficiency in most regions. The findings also provide policy makers with useful decision support insights for regional sustainable innovation, energy conservation and emission reduction policies. In addition, sustainable innovation governance should continue to be strengthened to promote and support the improvement of SIE.

Purpose: This study aimed to explore the test-retest reliability of fNIRS in measuring frontal and parietal cortices activation during straight walking and turning walking in older adults, in order to provide a theoretical foundation for selecting assessment tools for clinical research on motor control and some diseases such as Parkinson's disease in older adults. Methods: 18 healthy older participants (69.1 ± 0.7 years) were included in this study. The participants completed straight walking and figure-of-eight turning walking tasks at self-selected speeds. Intra-class correlation coefficients (ICCs) and Bland-Altman scatter plots were used to assess the test-retest reliability of oxyhemoglobin (HbO2) changes derived from fNIRS. p

Summary: Global warming has led to a surge in heat health risks (HHRs), the impacts of which are particularly pronounced in metropolitan areas of developing countries. In the current study, six metropolitan areas - Beijing, China; Cairo, Egypt; Jakarta, Indonesia; Mumbai, India; Rio de Janeiro, Brazil; and Tehran, Iran - were selected as the study area to further differentiate the built-up landscapes by utilizing the concept of local climate zones. Moreover, we assessed the similarities and differences in HHR associated with the landscape. Results revealed a 30.67% higher HHR in compact built-up landscapes than in the open built-up type. Urban green spaces played an effective but differentiated role in mitigating HHR. That is, low vegetation in urbanized areas and trees in suburban areas significantly mitigated HHR. Collectively, our findings emphasize the role of effective planning and management in addressing HHR and provide empirical support for implementing HHR mitigation and adaptation strategies.

This paper presents PyPSA-GB, a dataset and model of Great Britain’s (GB) power system encompassing historical years and the future energy scenarios developed by National Grid. It is the first fully open-source model implementation of the future GB power system with high spatial and temporal resolution, and data for future years up to 2050. Two power dispatch formulations can be optimised: (i) single bus unit commitment problem, and (ii) network constrained linear optimal power flow. The model is showcased through an example analysis of quantifying future wind curtailment in Scotland. PyPSA-GB provides an open-source basis for GB operational and planning studies, e.g., sector coupling and flexibility options.

Ferroptosis, distinct from apoptosis, necrosis, autophagy, and other types of cell death, is a novel iron-dependent regulated cell death characterized by the accumulation of lipid peroxides and redox imbalance with distinct morphological, biochemical, and genetic features. Dysregulation of iron homeostasis, the disruption of antioxidative stress pathways and lipid peroxidation are crucial in ferroptosis. Ferroptosis is involved in the pathogenesis of several cardiovascular diseases, including atherosclerosis, cardiomyopathy, myocardial infarction, ischemia-reperfusion injury, abdominal aortic aneurysm, aortic dissection, and heart failure. Therefore, a comprehensive understanding of the mechanisms that regulate ferroptosis in cardiovascular diseases will enhance the prevention and treatment of these diseases. This review discusses the latest findings on the molecular mechanisms of ferroptosis and its regulation in cardiovascular diseases, the application of ferroptosis modulators in cardiovascular diseases, and the role of traditional Chinese medicines in ferroptosis regulation to provide a comprehensive understanding of the pathogenesis of cardiovascular diseases and identify new prevention and treatment options.

Background: Epidemiological characteristics of human brucellosis (HB) have changed over the last decade. In this study, we depicted the spatiotemporal features of HB in Shenyang, China, from 2013 to 2022 and the objective was to visualise spatiotemporal patterns and identify high-risk regions with the purpose to provide evidence for HB prevention and control. Methods: We performed an observational epidemiological study using HB data obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression analysis was employed to determine the changing trends in the annual incidence. A vector boundary map of Shenyang was used to visualise spatial distribution. Spatial autocorrelation was identified using both global and local Moran's autocorrelation coefficients, while hotspot areas were determined using the Getis-Ord statistic. Results: A combined sum of 4103 HB cases were analysed, and the average level of annual incidence of HB was 5.52 per 100,000. The incidence of HB showed obvious seasonality, with a notable peak observed from April to July (summer peak). The annual incidence in Shenyang has been on the rise since 2013, with an annual percentage change (APC) of 6.39% (95%CI 1.29%, 12.39%). Xinmin County exhibited the most elevated average annual incidence rate, with Faku County ranking second. The average annual incidence in rural areas exhibited a significantly greater disparity compared to suburban areas (P

Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.

Purpose: This study aimed to compare the biomechanical effects of different bone cement distribution methods on osteoporotic vertebral compression fractures (OVCF). Patients and methods: Raw CT data from a healthy male volunteer was used to create a finite element model of the T12-L2 vertebra using finite element software. A compression fracture was simulated in the L1 vertebra, and two forms of bone cement dispersion (integration group, IG, and separation group, SG) were also simulated. Six types of loading (flexion, extension, left/right bending, and left/right rotation) were applied to the models, and the stress distribution in the vertebra and intervertebral discs was observed. Additionally, the maximum displacement of the L1 vertebra was evaluated. Results: Bone cement injection significantly reduced stress following L1 vertebral fractures. In the L1 vertebral body, the maximum stress of SG was lower than that of IG during flexion, left/right bending, and left/right rotation. In the T12 vertebral body, compared with IG, the maximum stress of SG decreased during flexion and right rotation. In the L2 vertebral body, the maximum stress of SG was the lowest under all loading conditions. In the T12-L1 intervertebral disc, compared with IG, the maximum stress of SG decreased during flexion, extension, and left/right bending and was basically the same during left/right rotation. However, in the L1-L2 intervertebral discs, the maximum stress of SG increased during left/right rotation compared with that of IG. Furthermore, the maximum displacement of SG was smaller than that of IG in the L1 vertebral bodies under all loading conditions. Conclusions: SG can reduce the maximum stress in the vertebra and intervertebral discs, offering better biomechanical performance and improved stability than IG.

Surface subsidence pits formed by mining disturbance are highly susceptible to slope instability under rainfall erosion, inducing underground debris flow disasters. To prevent and control underground debris flow disasters in a subsidence area, a test model of subsidence pit slope was established in accordance with the principle of similar simulation, and the erosion-resistant performance of moraine-cured slopes with different soil–slurry ratios and the law of runoff and sand production were investigated through the simulation of artificial rainfall and a simulation test of grouting. Results show that the initial rainfall production time increases exponentially with increasing soil-slurry ratio, while sediment production intensity decreases linearly with increasing rainfall duration. The evolution of soil erosion can be divided into five stages: impact infiltration, water-filled softening, stripping cutting, migration crossing, and steady flow equilibrium. Compared with in situ moraine, moraine particles after grouting between the generation of large amounts of Si–O–Si and Si–OH hydration products become loose and porous soil medium is transformed into a dense cemented structure. The soil-slurry ratio is 5:1, the sand-fixing effect increases by 28.8 times, the resistance of permeability increases by 11.3 times, and the grouting curing effect is remarkable. This study can provide technical support for the prevention and control of geological disasters in subsidence pits.

Summary: Although the impact of sleep loss on social behaviors has been widely observed in recent years, the mechanisms underpinning these impacts remain unclear. In this study, we explored the detrimental effects of sleep deprivation on reciprocity behavior as well as its underlying psychological and neuroimaging mechanisms by combining sleep manipulation, an interpersonal interactive game, computational modeling and neuroimaging. Our results suggested that after sleep deprivation, individuals showed reduced reciprocity behavior, mainly due to their reduced weights on communal concern when making social decisions. At neural level, we demonstrated that sleep deprivation’s effects were observed in the precuneus (hyperactivity) and temporoparietal junction, dorsal lateral prefrontal cortex (DLPFC) (both hypoactivity), and reduced reciprocity was also accounted for by increased precuneus-thalamus connectivity and DLPFC-thalamus connectivity. Our findings contributed to the understanding of the psychological and neuroimaging bases underlying the deleterious impact of sleep deprivation on social behaviors.

Summary: Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain. Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO). Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03). Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4). Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion’s Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Effects of 3 wt% RE (rare earth) addition on microstructures and mechanical properties of a high-pressure die casting Mg–8Zn–6Al (ZA86) alloy before and after aging treatment was thoroughly studied in this work. Microstructural characterizations present that RE addition has indiscernible influence on the well-defined dendrite structure and grain size, but would additionally introduce Al-RE intermetallic phases, which were identified as Al3RE and Al11RE. Simultaneously, two groups of Mg–Al–Zn ternary phases were detected in alloys with/without RE addition, while their volume fraction was clearly reduced by RE addition. After aging at 90 °C for 320 h, a large density of precipitates were observed particularly near grain/cell boundaries, and were identified as MgZn2, Mg4Zn7, and I-phase. Although RE addition seems to have no influence on the components of precipitates, it obviously improves their volume fraction and slightly increases their size. Finally, the yield strength of the ZA86 alloy after aging was improved by ∼33 MPa by RE addition. Therefore, the die cat ZA86 alloy exhibits high-strength and certain precipitation strengthening ability, and RE addition can significantly enhance the precipitation strengthening, accomplishing the highest yield strength in the reported HPDC magnesium alloys, being ∼267 MPa.

In higher plants, the shoot apical meristem produces lateral organs in a regular spacing (phyllotaxy) and timing (plastochron). The molecular analysis of mutants associated with phyllotaxy and plastochron would increase our understanding of the mechanism of shoot architecture formation. In this study, we identified mutant mnd8ynp5 that shows an increased rate of leaf emergence and a larger number of nodes in combination with a dwarfed growth habit from an EMS-treated population of the elite barley cultivar Yangnongpi 5. Using a map-based cloning strategy, the mnd8 gene was narrowed down to a 6.7-kb genomic interval on the long arm of chromosome 5H. Sequence analysis revealed that a C to T single-nucleotide mutation occurred at the first exon (position 953) of HORVU5Hr1G118820, leading to an alanine (Ala) to valine (Val) substitution at the 318th amino acid site. Next, HORVU5Hr1G118820 was defined as the candidate gene of MND8 encoding 514 amino acids and containing two multidrug and toxic compound extrusion (MATE) domains. It is highly homologous to maize Bige1 and has a conserved function in the regulation of plant development by controlling the leaf initiation rate. Examination of modern barely varieties showed that Hap-1 was the dominant haplotype and was selected in barley breeding around the world. Collectively, our results indicated that mnd8ynp5 is a novel allele of the HORVU5Hr1G118820 gene that is possibly responsible for the shortened plastochron and many noded dwarf phenotype in barley.

Chalcopyrite is the main Cu-containing mineral and cannot be separated well from pyrite using traditional xanthate collectors with large amounts of lime depressant, resulting in difficulties of the tailing treatment and associated precious metals recovery. Therefore, in this study, the green and odourless ethylenediamine tetramethylenephosphonic acid (EDTMPA) was introduced as a novel chalcopyrite collector. Flotation results from the binary mineral mixture and real ore demonstrated that EDTMPA could realize the selective separation of chalcopyrite from pyrite relative to ethyl xanthate (EX) without any depressants within the wide pH range of 6.0–11.0, and might replace the traditional high-alkaline lime process. Electrochemical and Fourier transform infrared spectra measurements indicated that the difference in adsorption performance of EDTMPA on chalcopyrite and pyrite was larger than that of EX, suggesting a better selectivity for EDTMPA. Density functional theory calculations demonstrated that there were stronger chemical bonds between P—O groups of EDTMPA and the Fe/Cu atoms on chalcopyrite in the form of a stable six-membered ring. Crystal chemistry calculations further revealed that the activity of metal atoms of chalcopyrite was higher than that of pyrite. Therefore, these basic theoretical results and practical application provide a guidance for the industrial application of EDTMPA in chalcopyrite flotation.

Tuberculosis (TB) remains a significant global health challenge, characterized by high incidence and mortality rates on a global scale. With the rapid advancement of computer-aided diagnosis (CAD) tools in recent years, CAD has assumed an increasingly crucial role in supporting TB diagnosis. Nonetheless, the development of CAD for TB diagnosis heavily relies on well-annotated computerized tomography (CT) datasets. Currently, the available annotations in TB CT datasets are still limited, which in turn restricts the development of CAD tools for TB diagnosis to some extent. To address this limitation, we introduce DeepPulmoTB, a CT multi-task learning dataset explicitly designed for TB diagnosis. To demonstrate the advantages of DeepPulmoTB, we propose a novel multi-task learning model, DeepPulmoTBNet (DPTBNet), for the joint segmentation and classification of lesion tissues in CT images. The architecture of DPTBNet comprises two subnets: SwinUnetR for the segmentation task, and a lightweight multi-scale network for the classification task. Furthermore, to enhance the model's capacity to capture TB lesion features, we introduce an improved iterative optimization algorithm that refines feature maps by integrating probability maps obtained in previous iterations. Extensive experiments validate the effectiveness of DPTBNet and the practicality of the DeepPulmoTB dataset.

Exosome-like nanovesicles isolated from edible plants (ELNs) have been proven to have multiple activities with anti-inflammatory and antioxidant potential beneficial effects, which play an important role in human health. However, ELNs from coarse cereals and legume grains were rarely reported. The aim of this study is to explore the effect of kidney bean derived exosome-like nanovesicles (KBELNs) on obesity induced by HFD. The KBELNs were isolated and characterized similarly to animal cell-derived exosome-like nanovesicles. Oral KBELNs significantly reduced body weight, liver weight, increased SCFAs and improved blood glucose and lipid levels in obese rats. And KBELNs increased the diversity of gut microbiota, and improved obesity by regulating the composition of gut microbiota, increasing the distribution of beneficial bacteria and enhancing the level of metabolite SCFAs. Our study provides important information for the anti-obesity effect of kidney beans, which offers a novel consideration for the improvement of obesity with KBELNs.

Background: The prognostic-related factors of lung invasive mucinous adenocarcinoma(IMA) are unclear because of its rarity. Various inflammation-based biomarkers were reported to predict the survival of malignant diseases. This study aims to explore the prognostic significance of the systemic immune-inflammation index(SII), which is calculated using absolute platelet, neutrophil, and lymphocyte counts, among patients with invasive mucinous adenocarcinoma. Methods: From January 2015 to December 2019, 106 patients were identified as having IMA accepted radical resection and enrolled in the retrospective study. We analyzed the overall survival and disease-free survival using the Kaplan-Meier method and log-rank test. Receiver operating characteristic curve was used to find the optimal SII cut-off values for survival. A Cox regression model was carried out for multivariable analyses. Results: The study cohort included 53 men and 53 women, with a mean age of 60 years (range 29 to 78 years, median 61 years). The median SII measured before surgery was 378.47 (range: 79.87–1701.97). ROC analyses revealed that the optimal cut-off values of SII was 379.43 for predicting both OS and DFS. An elevated SII (≥379.43) was observed in 52 patients (49.1 %), and was associated with younger age (P = 0.02), advanced T staging (P = 0.042), lymph node metastasis (P = 0.018) and pneumonic-type IMA (P = 0.018). Multivariable analysis showed that SII and pneumonic-type IMA were independent prognostic predictors of OS and DFS in radically resected IMA patients (P

Summary: Background: The pathology of keloid and especially the roles of bacteria on it were not well understood. Methods: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. Findings: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. Interpretation: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Flexible tissue modeling plays an important role in the field of telemedicine. It is related to whether the soft tissue deformation process can be accurately, real-time and vividly simulated during surgery. However, most existing models lack the unique biological characteristics. To solve this problem, we proposed a high-fidelity virtual liver model incorporating biological characteristics, such as the viscoelastic, anisotropic and nonlinear biological characteristics. Besides, to the best of our knowledge, our study is the first to introduce the viscoplasticity of biological tissues to improve the fidelity of the liver model. This mothod was proposed to describe the viscoplastic characteristics of the diseased liver resection process, when the liver is in a state of excessive deformation and loss of elasticity, however, there are few works focusing on this problem. The 3DMax2020 and OpenGL4.6 were used to build a liver surgery simulation platform, and the PHANTOM OMNI manual controller was used to sense the feedback force during the operation. The proposed model was verified from three aspects of accuracy, fidelity and real-time performance. The experimental results show that the proposed virtual liver model can enhance visual perception ability, improve deformation accuracy and fidelity.

Study region: Andun river basin of Southern China and 273 watersheds across the continental United States. Study focus: Owing to the data incompleteness and the changing environment, there is bias existing in the data driven models for streamflow prediction, greatly limiting their application in actual practice. In this paper, we incorporate the bias learning components into the data driven models to establish the mapping-bias-learning models, and design two groups of experiments, one in the Andun River basin in China and the other in 273 watersheds in the continental United States (CONUS). In the first group of experiments, we respectively apply three machine learning algorithms and one traditional statistical method to generate sixteen mapping-bias-learning models ae well as four mapping-learning-alone models. We also explore the effectiveness of different bias learning strategies, including multiple bias learning, stacking bias learning and incremental updating bias learning. In the second group of experiments, we apply the mapping-bias-learning models to the streamflow prediction in 273 watersheds of CONUS to verify the universality and robustness of the bias learning method. New hydrological insights for the region: The mapping-bias-learning models significantly outperform the mapping-learning-alone models, and the machine learning methods are superior to the traditional statistical method in term of the ability of bias learning. In addition, adopting the appropriate bias learning strategies can further improve the streamflow forecast performance of data-driven models. The bias learning method is applicable to various watersheds with different hydrological conditions and play efficient roles at different streamflow levels. The median of MRE drops from 0.156 for mapping-learning-alone models to 0.131 for mapping-bias-learning models, while median of NSE increases from 0.918 for mapping-learning-alone models to 0.932 for mapping-bias-learning models. More inspiringly, the bias learning method can still play roles in data driven models under the environmental conditions that never occurred before, suggesting its remarkable superiority. This study highlights the power of the bias learning method for data driven models in streamflow prediction, and the promising prospect of the combination between bias learning and machine learning methods in hydrological modelling.

DNA barcoding has been widely used for herb identification in recent decades, enabling safety and innovation in the field of herbal medicine. In this article, we summarize recent progress in DNA barcoding for herbal medicine to provide ideas for the further development and application of this technology. Most importantly, the standard DNA barcode has been extended in two ways. First, while conventional DNA barcodes have been widely promoted for their versatility in the identification of fresh or well-preserved samples, super-barcodes based on plastid genomes have rapidly developed and have shown advantages in species identification at low taxonomic levels. Second, mini-barcodes are attractive because they perform better in cases of degraded DNA from herbal materials. In addition, some molecular techniques, such as high-throughput sequencing and isothermal amplification, are combined with DNA barcodes for species identification, which has expanded the applications of herb identification based on DNA barcoding and brought about the post-DNA-barcoding era. Furthermore, standard and high-species coverage DNA barcode reference libraries have been constructed to provide reference sequences for species identification, which increases the accuracy and credibility of species discrimination based on DNA barcodes. In summary, DNA barcoding should play a key role in the quality control of traditional herbal medicine and in the international herb trade.