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Abstract G protein-coupled receptor 4 (GPR4) belongs to the subfamily of proton-sensing GPCRs (psGPCRs), which detect pH changes in extracellular environment and regulate diverse physiological responses. GPR4 was found to be overactivated in acidic tumor microenvironment as well as inflammation sites, with a triad of acidic residues within the transmembrane domain identified as crucial for proton sensing. However, the 3D structure remains unknown, and the roles of other conserved residues within psGPCRs are not well understood. Here we report cryo-electron microscopy (cryo-EM) structures of active zebrafish GPR4 at both pH 6.5 and 8.5, each highlighting a distribution of histidine and acidic residues at the extracellular region. Cell-based assays show that these ionizable residues moderately influence the proton-sensing capacity of zebrafish GPR4, compared to the more significant effects of the triad residues. Furthermore, we reveal a cluster of aromatic residues within the orthosteric pocket that may propagate the signaling to the intercellular region via repacking the aromatic patch at the central region. This study provides a framework for future signaling and functional investigation of psGPCRs.

The application of microbially induced carbonate precipitation (MICP) in clayey soils has attracted much attention, and many studies used clay as an additive to enhance microbial mineralization efficiency in sandy soils. Within the sand-clay-bacteria-calcite system, the property and content of clay play crucial roles in affecting bacterial growth and calcite formation. More important, bentonite is particularly sensitive to changes in the geochemical environment. In this study, the sand-bentonite mixtures were treated by biostimulated MICP, aiming to provide insights into the behavior of this system. The bacterial activity and cementation pattern at different bentonite contents were evaluated through a series of tests such as enrichment tests, unconfined compressive strength (UCS) tests, cementation content measurements, mercury intrusion porosimetry (MIP) tests, scanning electron microscopy (SEM) observations, and energy dispersive X-ray spectroscopy (EDS) analyses. The findings showed that the bentonite presence promoted the enrichment of indigenous ureolytic bacteria, with lower bentonite levels enhancing ureolytic activity. Macroscopic and microscopic characterization indicated that the bentonite-coating sand structure was more conducive to the formation of large-sized calcite crystals capable of cementing soil particles compared to sand-supported and bentonite-supported structures. Additionally, excessive calcium ions (Ca2+) concentrations in the cementitious solution would lead to predominant calcite deposition on soil particle surfaces, contributing minimally to strength improvement.

Abstract Cervical cancer is the fourth most common malignant tumor among women globally, posing a significant threat to women’s health. In 2022, approximately 600,000 new cases were reported, and 340,000 deaths occurred due to cervical cancer. Magnetic resonance imaging (MRI) is the preferred imaging method for diagnosing, staging, and evaluating cervical cancer. However, manual segmentation of MRI images is time-consuming and subjective. Therefore, there is an urgent need for automatic segmentation models to identify cervical cancer lesions in MRI scans accurately. All MRIs in our research are from cervical cancer patients diagnosed by pathology at Tongren City People’s Hospital. Strict data selection criteria and clearly defined inclusion and exclusion conditions were established to ensure data consistency and accuracy of research results. The dataset contains imaging data from 122 cervical cancer patients, with each patient having 100 pelvic dynamic contrast-enhanced MRI scans. Annotations were jointly completed by medical professionals from Universiti Putra Malaysia and the Radiology Department of Tongren City People’s Hospital to ensure data accuracy and reliability. Additionally, a novel computer-aided diagnosis model named SwinUNeCCt is proposed. This model incorporates (i) A bidirectional hash-based agent multi-head self-attention mechanism, which optimizes the interaction between local and global features in MRI, aiding in more accurate lesion identification. (ii) Reduced computational complexity of the self-attention mechanism. The effectiveness of the SwinUNeCCt model has been validated through comparisons with state-of-the-art 3D medical models, including nnUnet, TransBTS, nnFormer, UnetR, UnesT, SwinUNetR, and SwinUNeLCsT. In semantic segmentation tasks without a classification module, the SwinUNeCCt model demonstrates excellent performance across multiple key metrics: achieving a 95HD of 6.25, an IoU of 0.669, and a DSC of 0.802, all of which are the best results among the compared models. Simultaneously, SwinUNeCCt strikes a good balance between computational efficiency and model complexity, requiring only 442.7 GFLOPs of computational power and 71.2 M parameters. Furthermore, in semantic segmentation tasks that include a classification module, the SwinUNeCCt model also exhibits powerful recognition capabilities. Although this slightly increases computational overhead and model complexity, its performance surpasses other comparative models. The SwinUNeCCt model demonstrates excellent performance in semantic segmentation tasks, achieving the best results among state-of-the-art 3D medical models across multiple key metrics. It balances computational efficiency and model complexity well, maintaining high performance even with the inclusion of a classification module.

Based on nine C-band Doppler radar observations of Heilongjiang Province and conventional data from 2010 to 2021， combined with 1-h interval ERA5 reanalysis data of 0.25°×0.25° from the European Center for Medium-Range Weather Forecasts， the types and activity characteristics of mesoscale precipitation bands associated with extratropical cyclones in Heilongjiang Province are statistically analyzed， and the similarities and differences in the environment fields of two types of mesoscale precipitation bands are compared through typical cases.The main results are： （1） Mesoscale precipitation bands are primarily divided into single， multi， transitory， and nonbanded.Precipitation bands are mainly located in southern and northeastern Heilongjiang and the northwest and northeast quadrants of surface cyclones， within 900 km from the cyclone centers， and occur in the mature stage of cyclones.The main movement types of mesoscale precipitation bands are laterally translating and hybrid.（2） Vertical profiles of physical quantities can well reflect differences in precipitation intensity of different precipitation bands.Single-banded bands have the most excellent low-level specific humidity and frontogenesis， causing the heaviest precipitation.Non-banded bands have extensively weaker low-level frontogenesis than single-banded bands， with maximum specific humidity near 800 hPa， causing a wide range of precipitation and a weaker precipitation intensity than single-banded bands.（3） The analysis of cases shows that both single-banded and multi-banded bands are located on the north side of the intense 850-hPa warm advection， the northeast quadrant of the surface cyclone， in a small moist symmetric stable or moist symmetric unstable environment.The direction of the mesoscale precipitation band is parallel to the frontogenesis.The differences between them are as follows： for the single-banded band， deformation leads to strong frontogenesis and the upward movement concentrated on a small area， accompanying the development and movement of the low-level low and the surface cyclone， while for the multi-banded， weak deformation and shallow frontogenesis accompanying little movement and intensity change， intense upper-level divergence and low-level warm advection caused more extensive upward motion with multiple upward centers， corresponding to multi bands.

Abstract Background Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability. Methods A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods. Results Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate. Conclusions This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Highlights We classified the carriers that built cancer nanovaccines, discussed their diversified applications and coincidently compared their advantages and disadvantages. Various cellular targets that guide the design and engineering of cancer nanovaccines are categorized and their characteristics and benefits are highlighted. The clinical cases and encountered challenges in cancer nanovaccines are discussed, during which reasonable solutions and future research direction are provided.

Neuron-specific enolase (NSE) is currently the most reliable biomarker for small cell lung cancer (SCLC), which is important for disease monitoring, clinical evaluation and diagnosis. However, traditional methods suffer from various disadvantages, including instability, complexity, time-consuming operations, and the necessity for standards. In this study, we developed a calibration-free concentration analysis (CFCA) method based on surface plasmon resonance (SPR) technology, to accurately quantify the active concentration of NSE without relying on any standards. Based on the principle of CFCA, the active concentration of NSE can be calculated by observing binding rate variations at two flow rates under partial mass transport limitation and combining it with the known diffusion coefficient of the NSE. Using the method of CFCA, the active concentration of NSE was determined was only 0.48 mg/mL with an intra-day repeatability of 4.75%. The method has the advantages of simplicity, rapidity, realistic analysis and ease of implementation of high-throughput automated detection. Therefore, the method is expected to become the main measurement method for protein active concentration, which will be beneficial for the development of active protein standards.

Purpose Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells.Methods We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity.Results Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced.Conclusion YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.

Resistance to sorafenib, an effective first-line treatment for advanced hepatocellular carcinoma (HCC), greatly compromised the prognosis of patients. The extracellular matrix is one of the most abundant components of the tumor microenvironment. Beyond acting as a physical barrier, it remains unclear whether cell interactions and signal transduction mediated by the extracellular matrix contribute to sorafenib resistance. With the analysis of primary HCC organoid RNA-seq data combined with in vivo and in vitro experiments validation, we discovered that fibronectin extra domain A (FN-EDA) derived from cancer-associated fibroblasts played a critical role in sorafenib resistance. Mechanistically, FN-EDA stimulates the up-regulation of the key one-carbon metabolism enzyme SHMT1 in HCC cells via the TLR4/NF-κB signaling pathway, thereby countering the oxidative stress induced by sorafenib. Moreover, we reinforced the clinical significance of our discoveries by conducting in vivo assays with an immunodeficiency subcutaneous xenograft tumor model, which was established using primary cancer-associated fibroblasts derived from clinical HCC tissues, and through the analysis of HCC samples obtained from The Cancer Genome Atlas (TCGA) database. Our findings suggest that targeting the FN-EDA/SHMT1 pathway could be a potential strategy to improve sorafenib responsiveness in HCC patients.

This paper builds on exploring the applications of biomediated pathways to solve geotechnical challenges. First, the state of the art of biological remediation strategies including microbial remediation and phytoremediation have been introduced and critically reviewed in the context of decontaminating the soils. Next, biopolymerisation, biomineralisation and bioneutralisation processes have been depicted with a special emphasis on the applications including but not limited to soil stabilisation, soil erosion prevention, anti-desertification and pH neutralisation. Each of these methods have their own limitations and bottlenecks while scaling up, and these challenges have been summarised and some possible paths to overcome the challenges have also been discussed. The state of the art of electromagnetic (EM) monitoring methods to capture the effects of biomediation on spatio-temporal soil properties are then highlighted as a non-invasive and rapid pathway to track the progress of biomediated soil processes. Finally, each of the technologies discussed have been evaluated for their maturity level using the principles of technology readiness level (TRL). A majority of the technologies amounting to around 77% are still in the TRL 4–7, i.e. in the valley of death. It is thus evident that development of these technologies needs to be supported with appropriate funding for improving their maturity to a level of industrial deployment.

Objectives: The aim of this study was to investigate the molecular mechanism underlying odontoblast damage repair in dentin hypersensitivity (DH) and the role of Yes-associated protein (YAP) in this process. Methods: The DH model was constructed in Sprague-Dawley (SD) rats, and the in vivo expression of Piezo1, Integrin αvβ3, YAP, and dentin sialophosphoprotein (DSPP) was detected by immunohistochemistry. COMSOL Multiphysics software was used to simulate the dentinal tubule fluid flow velocity and corresponding fluid shear stress (FSS) on the odontoblast processes. MDPC-23 cells were cultured in vitro and loaded with a peristaltic pump for 1 hour at FSS values of 0.1, 0.3, 0.5, and 0.7 dyne/cm2. The expression of Piezo1, Integrin αvβ3, and YAP was detected by immunofluorescence. Verteporfin (a YAP-specific inhibitor) was utilised to confirm the effect of YAP on the expression of dentineogenesis-related protein under FSS. Results: The level and duration of external mechanical stimuli have an effect on the functional expression of odontoblasts. In DH, the harder the food that is chewed, the faster the flow of the dentinal tubule fluid and the greater the FSS on the odontoblast processes. The expression of Piezo1, Integrin αvβ3, and YAP can be promoted when the FSS is less than 0.3 dyne/cm2. After YAP inhibition, the DSPP protein expression level was reduced at 0.3 dyne/cm2 FSS. Conclusions: These results suggest that appropriate FSS can enhance the expression of odontoblast-related factors in odontoblasts via the Piezo1–Integrin αvβ3–YAP mechanotransduction pathway and the YAP appears to play an essential role in the response of odontoblasts to external mechanical stimuli.

Abstract Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.

In this study, soft gel stripping experiments were conducted under different temperatures and flow velocity conditions by a flow loop. The flow area of pipes increased with an increase in flow velocity. However, partial or complete removal of soft gels occurred when flow velocity increased to a critical point. The hydrodynamic force from oil flow, adhesive contact force and yield stress of soft gels were calculated and compared. The hydrodynamic force increased with an increase in flow velocity. Under the dissolution and shear effect, the flow area showed a step-wise increase when hydrodynamic force did not meet the requirements of adhesion failure and structural failure. The soft gels were stripped completely when the force met the requirements. The lower strength of soft gels resulted in lower requirements of adhesion failure and structural failure. Thus, accumulation problems of soft gels can be solved by changing flow parameters.

The high momentum tail (HMT) in the momentum distribution of nucleons above the Fermi surface has been regarded as an evidence of short-range correlations (SRCs) in atomic nuclei. It has been showcased recently that the np Bremsstrahlung radiation in heavy ion reactions can be used to extract HMT information. The Richardson-Lucy (RL) algorithm is introduced to the reconstruction of the original Bremsstrahlung γ-ray energy spectrum from experimental measurements. By solving the inverse problem of the detector response to the γ-rays, the original energy spectrum of the Bremsstrahlung γ in 25 MeV/u 86Kr + 124Sn has been reconstructed and compared to the isospin- and momentum-dependent Boltzmann-Uehling-Uhlenbeck (IBUU) simulations. The analysis based on hypothesis test suggests the existence of the HMT of nucleons in nuclei, in accordance with the previous conclusions. With its effectiveness being demonstrated, it is feasible to apply the RL algorithm in future experiments of measuring the Bremsstrahlung γ-rays in heavy ion reactions.

Background The severity of acute gastrointestinal injury (AGI) is a critical determinant of survival in sepsis. However, there is no specifically interventional management for gastrointestinal dysfunction. Toll-like Receptor 4 (TLR4) is an important contributor to sepsis-induced multiple organ dysfunction syndrome. So, we investigated the effect of TLR4 on leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) + cells and goblet cells and its potential mechanism. Methods A cecal ligation and puncture (CLP) model reflecting the development of clinical sepsis was developed. Tak-242, a TLR4 inhibitor, was administered to septic rats at a dose of 3 mg/kg via intraperitoneal injection. Immunohistochemistry was performed to detect TLR4 and Lgr5+ cells. AB-PAS staining was performed to detect goblet cells. MUC1 and MUC2 secreted by goblet cells, biomarkers of endoplasmic reticulum (ER) stress and inflammatory cytokines in the intestine were detected by western blotting and real-time PCR. Results We found that the upregulation of the TLR4/NF-κB signaling pathway activated intestinal inflammatory response in sepsis. Meanwhile, the structure of intestinal mucosa was destroyed, Lgr5+ cells and goblet cells count were significantly reduced, and the secretory function of goblet cells also decreased. Further studies have found that TLR4 increased the levels of activating transcription factor-6 (ATF6), XBP1, ER chaperone (Bip) and CHOP, but did not activate the protein kinase RNA (PKR)-like ER kinase (P-PERK). Conclusion We concluded that the inhibition of TLR4/NF-κB signaling pathway can reduce intestinal inflammatory response, protect intestinal mucosa, protect Lgr5+ cells, goblet cells and relieve ER stress. Our findings suggest that Tak-242 protects Lgr5+ cells and goblet cells after sepsis, partly may be through the suppression of ER stress. Thus, inhibition of TLR4-mediated ER stress may be a promising therapy of septic AGI.

In this study, the process conditions, physicochemical properties, structural composition and activity of polysaccharides isolated from leechee peel (LPP) by ultrasound-assisted extraction (UAE) with enzyme and alkali solution extraction (ASE) were compared. The results showed that the total sugar content of LPP extracted by UAE accounted for 75.65 %, which was significantly higher than that extracted by alkali solution. The optimum conditions were as follows: extraction temperature of 68.78 ℃, ultrasonic enzymolysis time of 39.68 min, pectinase dosage of 4.03 %, solid–liquid ratio of 1:30 g/mL, and ultrasonic power of 360 W. The antioxidant activities and structure of leechee peel polysaccharide (LPP) prepared under different conditions were compared. It was found that UAE-LPP was an α-type polysaccharide containing 15.83 % uronic acid. Moreover, LPP extracted by UAE showed strong activity in anti-lipid peroxidation and reducing ability. Ultrasound-assisted enzymatic method is an effective means to improve the content and activity of natural plant polysaccharides, and this method has the advantages of short time-consuming, simple process and easy operation, which can greatly improve the utilization rate of polysaccharides and lay a theoretical and scientific basis for the development and utilization of LPP.

Fertilization significantly influences soil quality and its sustainable use in urban garden maintenance. The widespread application of inorganic fertilizers has raised ecological concerns due to their potential environmental impacts. Organic fertilizers, while beneficial, often have slow effects and are costly. Biofertilizers, with their eco-friendly nature and low carbon footprint, are gaining attention for their multifaceted role in supporting plant growth. Despite the focus on fruit trees, vegetables, and medicinal plants, ornamental plants have been understudied. This study aims to evaluate the efficacy of a novel microbial fertilizer, ‘natural soil biotin’, on Rhododendron plants, specifically the Azalea hybrid ‘Carnation’. The study employed a comparative approach to assess the impact of different fertilization strategies on soil properties, microbial diversity, enzyme activity, plant morphology, and physiological parameters. The application of ‘natural soil biotin’ was compared with the use of inorganic and organic fertilizers. The combined application of ‘natural soil biotin’ was found to effectively enhance soil properties and mitigate the impact of other fertilizers on soil pH. It also improved the relative abundance of beneficial microbial groups such as Proteobacteria, Ascomycota, and Basidiomycota. Furthermore, the mixed application significantly increased the activities of urease and sucrase in Rhododendron plants, which promoted their growth, development, and stress resistance. The results indicate that the mixed application of ‘natural soil biotin’ with inorganic and organic fertilizers not only improved the soil quality but also enhanced the efficiency of fertilizer utilization. This approach led to increased economic and environmental benefits in Rhododendron cultivation. The findings contribute to the foundation for soil improvement and ecological restoration, suggesting that ‘natural soil biotin’ could be a promising alternative or supplement to traditional fertilization methods in sustainable landscape architecture.

BackgroundChronic hepatitis B (CHB) imposes substantial economic and social burdens globally. The management of CHB involves intricate monitoring and adherence challenges, particularly in regions like China, where a high prevalence of CHB intersects with health care resource limitations. This study explores the potential of ChatGPT-3.5, an emerging artificial intelligence (AI) assistant, to address these complexities. With notable capabilities in medical education and practice, ChatGPT-3.5’s role is examined in managing CHB, particularly in regions with distinct health care landscapes. ObjectiveThis study aimed to uncover insights into ChatGPT-3.5’s potential and limitations in delivering personalized medical consultation assistance for CHB patients across diverse linguistic contexts. MethodsQuestions sourced from published guidelines, online CHB communities, and search engines in English and Chinese were refined, translated, and compiled into 96 inquiries. Subsequently, these questions were presented to both ChatGPT-3.5 and ChatGPT-4.0 in independent dialogues. The responses were then evaluated by senior physicians, focusing on informativeness, emotional management, consistency across repeated inquiries, and cautionary statements regarding medical advice. Additionally, a true-or-false questionnaire was employed to further discern the variance in information accuracy for closed questions between ChatGPT-3.5 and ChatGPT-4.0. ResultsOver half of the responses (228/370, 61.6%) from ChatGPT-3.5 were considered comprehensive. In contrast, ChatGPT-4.0 exhibited a higher percentage at 74.5% (172/222; P

Abstract Graphene films grown by the chemical vapor deposition (CVD) method suffer from contamination and damage during transfer. Herein, an innovative ice‐enabled transfer method under an applied electric field and in the presence of Cu2O (or Cu2O‐Electric‐field Ice Transfer, abbreviated as CEIT) is developed. Ice serves as a pollution‐free transfer medium while water molecules under the electric field fully wet the graphene surface for a bolstered adhesion force between the ice and graphene. Cu2O is used to reduce the adhesion force between graphene and copper. The combined methodology in CEIT ensures complete separation and clean transfer of graphene, resulting in successfully transferred graphene to various substrates, including polydimethylsiloxane (PDMS), Teflon, and C4F8 without pollution. The graphene obtained via CEIT is utilized to fabricate field‐effect transistors with electrical performances comparable to that of intrinsic graphene characterized by small Dirac points and high carrier mobility. The carrier mobility of the transferred graphene reaches 9090 cm2 V−1 s−1, demonstrating a superior carrier mobility over that from other dry transfer methods. In a nutshell, the proposed clean and efficient transfer method holds great potential for future applications of graphene.

Abstract Xanthomonas oryzae pv. oryzae (Xoo) injects major transcription activator-like effectors (TALEs) into plant cells to activate susceptibility (S) genes for promoting bacterial leaf blight in rice. Numerous resistance (R) genes have been used to construct differential cultivars of rice to identify races of Xoo, but the S genes were rarely considered. Different edited lines of rice cv. Kitaake were constructed using CRISPR/Cas9 gene-editing, including single, double and triple edits in the effector-binding elements (EBEs) located in the promoters of rice S genes OsSWEET11a, OsSWEET13 and OsSWEET14. The near-isogenic lines (NILs) were used as tracers to detect major TALEs (PthXo1, PthXo2, PthXo3 and their variants) in 50 Xoo strains. The pathotypes produced on the tracers determined six major TALE types in the 50 Xoo strains. The presence of the major TALEs in Xoo strains was consistent with the expression of S genes in the tracers, and it was also by known genome sequences. The EBE editing had little effect on agronomic traits, which was conducive to balancing yield and resistance. The rice-tracers generated here provide a valuable tool to track major TALEs of Xoo in Asia which then shows what rice cultivars are needed to combat Xoo in the field.

BackgroundThe staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. ObjectiveTo explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. MethodsFrom September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. ResultsOf 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P25, P75) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P25, P75) psychological resilience score was 24.00 (20.00, 30.00) and the median (P25, P75) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P

Objective Carbonate rocks have a significant carbon sink effect in water cycle. Since karst landforms are widely distributed in China, research on the potential of karst carbon sinks plays an important role in formulating regional strategies for increasing carbon sinks. Methods In this study, groundwater monitoring points in Hubei Province, which is located in the karst area of Southwest China, were selected. Quantitative calculations and method comparisons were performed based on the hydrochemical runoff method and the infiltration-equilibrium chemistry method. The spatial pattern and magnitude of karst carbon sinks in the hilly mountains of Hubei Province from 2019 to 2021 were evaluated via ArcGIS spatial analysis techniques. Additionally, the most suitable method for estimating karst carbon sinks at the regional scale were explored, the comprehensive analysis of the drivers of karst carbon sinks was performed, and the potential for increasing sinks were explored. Results The results showed that: (1) the intensity of carbon sinks estimated by the infiltration-equilibrium chemistry method were 2020>2019>2021. The total amount of karst carbon sinks in wet year (2020) was approximately 6 times of that in dry year (2019). The average annual carbon sink intensity in the three years was 12.84 t/(km2·a) and the annual total amount of carbon reached 163.89×104 t/a; (2) the infiltration-equilibrium chemistry method was more accurate in calculation results and simpler in data acquisition than the hydrochemical runoff method, and had a certain universality at both large and small spatial scales; (3) the change in carbon sinks was highly dynamic. The extent of changes in carbon sinks under climate change was mainly determined by runoff depth, with the intensity of carbon sinks increasing with runoff depth, while land use regulated the intensity of carbon sinks in karst processes; and (4) the karstification is strong in southwestern Hubei Province, so a pilot field of karst carbon sinks could be established within the area to quantitatively evaluate artificial interventions to increase carbon sinks. Conclusion This study not only provides an accurate and easy-to-use method for estimating karst carbon sinks, but also determines the magnitude and spatial pattern of karst carbon sinks in Hubei Province and figures out the coupling effect of the driving factors of carbon sink intensity, which demonstrates the complexity and anthropogenic control lability of karst carbon sinks. The results of this study provides a reliable scientific basis for the formulation of environmental protection policies and artificial sink increase measures.

Objectives: The aim of this research was to investigate the functions of Piezo channels in dentin defect, including mechanical signalling and odontoblast responses. Methods: Rat dentin-defect models were constructed, and spatiotemporal expression of Piezo proteins was detected in the pulpo-dentinal complex. Real-time polymerase chain reaction (rtPCR) was used to investigate the functional expression pattern of Piezo channels in odontoblasts. Moreover, RNA interference technology was employed to uncover the underlying mechanisms of the Piezo-driven inflammatory response and repair under fluid shear stress (FSS) conditions in vitro. Results: Piezo1 and Piezo2 were found to be widely expressed in the odontoblast layer and dental pulp in the rat dentin-defect model during the end stage of reparative dentin formation. The expression levels of the Piezo1 and Piezo2 genes in MDPC-23 cells were high in the initial stage under FSS loading and then decreased over time. Moreover, the expression trends of inflammatory, odontogenic, and mineralisation genes were generally contrary to those of Piezo1 and Piezo2 over time. After silencing of Piezo1/Piezo2, FSS stimulation resulted in significantly higher expression of inflammatory, odontogenesis, and mineralisation genes in MDPC-23 cells. Finally, the expression of genes involved in the integrin β1/ERK1 and Wnt5b/β-catenin signalling pathways was changed in response to RNA silencing of Piezo1 and Piezo2. Conclusions: Piezo1 and Piezo2 may be involved in regulating the expression of inflammatory and odontogenic genes in odontoblasts stimulated by FSS.

Abstract Tea is an indispensable beverage in people’s daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P

Objective Apart from the role of the retinoblastoma gene, the genomic events associated with poor outcomes in patients with ophthalmic tumors are poorly understood. Methods We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis. Results We identified four clearly causative genes ( TP53, PTCH1, SMO, BAP1 ). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2 , and BRCA2 , and high-frequency gene analysis identified several genes, including TP53, TTN , and MUC16 . Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD , ELANE , HBA1 , and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis. Conclusions TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A , and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.

Objectives The aim of this analysis was to investigate the worldwide distribution and trends in the burden of female infertility (FI).Design and setting Analysis of cross-sectional data from 1990 to 2019 from the Global Burden of Disease (GBD) Study 2019.Participants Adults aged 20–49 years in various geographical regions, Sociodemographic Index (SDI) levels and populations across 204 countries worldwide.Outcome measures Disability-adjusted life years (DALYs), age-standardised DALY rates and estimated annual percentage changes (EAPCs) for FI over the research period.Results The global burden of FI, as measured by DALYs and age-standardised DALY rates among adults aged 20–49 years, exhibited an upward trend from 1990 to 2019. Regions such as Tropical Latin America (EAPC: 3.76, 95% CI 2.76 to 4.77), South Asia (EAPC: 1.74, 95% CI 1.01 to 2.48) and Andean Latin America (EAPC: 8.54, 95% CI 6.79 to 10.32) had higher DALYs. The age-standardised DALY rates notably increased in low-middle-SDI and low-SDI countries, with EAPCs of 1.42 (95% CI 0.76 to 2.10) and 1.25 (95% CI 0.30 to 2.21), respectively. Despite lower overall DALYs in high-SDI countries, they experienced the highest EAPC in DALYs (1.57, 95% CI 1.30 to 1.83) during the period 1990–2019. China and India consistently had the highest DALYs for FI globally in both 1990 and 2019, while Africa and Latin America bore a significantly greater burden of the disease compared with other regions.Conclusion The GBD Study data on FI among adults aged 20–49 years revealed a rising global trend in FI from 1990 to 2019, with notable variations across different regions.

IntroductionDendrolimus punctatus, a major pest endemic to the native Pinus massoniana forests in China, displays major outbreak characteristics and causes severe destructiveness. In the context of global climate change, this study aims to investigate the effects of climatic variations on the distribution of D. punctatus and its host, P. massoniana. MethodsWe predict their potential suitable distribution areas in the future, thereby offering a theoretical basis for monitoring and controlling D. punctatus, as well as conserving P. massoniana forest resources. By utilizing existing distribution data on D. punctatus and P. massoniana, coupled with relevant climatic variables, this study employs an optimized maximum entropy (MaxEnt) model for predictions. With feature combinations set as linear and product (LP) and the regularization multiplier at 0.1, the model strikes an optimal balance between complexity and accuracy.ResultsThe results indicate that the primary climatic factors influencing the distribution of D. punctatus and P. massoniana include the minimum temperature of the coldest month, annual temperature range, and annual precipitation. Under the influence of climate change, the distribution areas of P. massoniana and its pests exhibit a high degree of similarity, primarily concentrated in the region south of the Qinling−Huaihe line in China. In various climate scenarios, the suitable habitat areas for these two species may expand to varying degrees, exhibiting a tendency to shift toward higher latitude regions. Particularly under the high emission scenario (SSP5-8.5), D. punctatus is projected to expand northwards at the fastest rate. DiscussionBy 2050, its migration direction is expected to closely align with that of P. massoniana, indicating that the pine forests will continue to be affected by the pest. These findings provide crucial empirical references for region-specific prevention of D. punctatus infestations and for the rational utilization and management of P. massoniana resources.

Abstract Liver metastasis is the major reason for most of colorectal cancer (CRC) related deaths. Accumulating evidence indicates that CRC patients with non-alcoholic fatty liver disease (NAFLD) are at a greater risk of developing liver metastasis. With the growing prevalence of NAFLD, a better understanding of the molecular mechanism in NAFLD-driven CRC liver metastasis is needed. In this study, we demonstrated that NAFLD facilitated CRC liver metastasis as a metabolic disorder and promoted the stemness of metastatic CRC cells for their colonization and outgrowth in hepatic niches. Metabolically, the lipid-rich microenvironment in NAFLD activated de novo palmitate biosynthesis in metastatic CRC cells via upregulating fatty acid synthase (FASN). Moreover, increased intracellular palmitate bioavailability promoted EGFR palmitoylation to enhance its protein stability and plasma membrane localization. Furthermore, we demonstrated that the FDA-approved FASN inhibitor orlistat could reduce NAFLD-activated endogenous palmitate production, thus inhibiting palmitoylation of EGFR to suppress CRC cell stemness and restrict liver metastasis in synergy with conventional chemotherapy. These findings reveal that the NAFLD metabolic microenvironment boosts endogenous palmitate biosynthesis in metastatic CRC cells and promotes cell stemness via EGFR palmitoylation, and FASN inhibitor orlistat could be a candidate adjuvant drug to suppress liver metastasis in CRC patients with NAFLD.

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Abstract The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.

Potatoes are typically seeded as tubers, and their slow sprouting significantly impacts production. Therefore, the effects of polyacrylamide (20 g·L−1, 30 g·L−1, and 40 g·L−1) as a seed potato dressing on sprouting, seedling growth, and biomass were investigated. The phytohormone content, respiratory intensity, and starch metabolism enzyme activity were analyzed to elucidate the physiological mechanisms involved. The sprouting rate significantly increased after 20 g·L−1 and 30 g·L−1 treatments by 40.63% and 15.63%, respectively. The sprouting energy was the highest (52.0%) at 20 g·L−1, 7.67 times higher than the control. The 20 g·L−1 and 30 g·L−1 treatments also promoted emergence and growth, with the emergence rate increasing by 18.18% and 27.27% and growth increasing by over 8.1% and 11.9%, respectively. These effects were related to changes in phytohormone content and accelerated starch conversion. After treatment, the auxin and cytokinin contents in the apical buds increased significantly at the germination initiation stage, and during the germination and vigorous growth phases, the auxin, cytokinin, and gibberellin contents increased. Polyacrylamide treatment activated α-amylase and promoted starch degradation, increasing soluble sugar content to provide nutrients and energy for sprouting. This study provides a promising approach for promoting potato tuber sprouting and seedling growth.

Abstract Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal-related death in premature infants. Its etiology is multifactorial, with intestinal dysbiosis playing a major role. Probiotics are a logical preventative therapy for NEC, however their benefits have been inconsistent. We previously developed a novel probiotic delivery system in which planktonic (free-living) Limosilactobacillus reuteri (Lr) is incubated with biocompatible dextranomer microspheres (DM) loaded with maltose (Lr-DM-maltose) to induce biofilm formation. Here we have investigated the effects of Lr-DM-maltose in an enteral feed-only piglet model of NEC. We found a significant decrease in the incidence of Definitive NEC (D-NEC), death associated with D-NEC, and activated microglia in the brains of piglets treated with Lr-DM-maltose compared to non-treated piglets. Microbiome analyses using 16S rRNA sequencing of colonic contents revealed a significantly different microbial community composition between piglets treated with Lr-DM-maltose compared to non-treated piglets, with an increase in Lactobacillaceae and a decrease in Clostridiaceae in Lr-DM-maltose-treated piglets. Furthermore, there was a significant decrease in the incidence of D-NEC between piglets treated with Lr-DM-maltose compared to planktonic Lr. These findings validate our previous results in rodents, and support future clinical trials of Lr in its biofilm state for the prevention of NEC in premature neonates.

Abstract Although there is evidence for the generosity of high-status individuals, there seems to be a strong perception that the elites are selfish and contribute little to others’ welfare, and even less so than poorer people. We argue that this perception may derive from a gap between normative and empirical expectations regarding the behavior of the elites. Using large-scale survey experiments, we show that high-status individuals are held to higher ethical standards in both the US and China, and that there is a strong income gradient in normatively expected generosity. We also present evidence for a gap between people’s normative expectations of how the rich should behave, and their empirical expectations of how they actually do: empirical expectations are generally lower than both normative expectations and actual giving.

The high momentum tail (HMT) of nucleons, as a signature of the short-range correlations in nuclei, has been investigated by the high-energy bremsstrahlung γ rays produced in 86Kr+124Sn at 25 MeV/nucleon. The energetic photons are measured by a CsI(Tl) hodoscope mounted on the spectrometer CSHINE. The energy spectrum ≥35 MeV can be reproduced by the Isospin- and Momentum-Dependent Boltzmann-Uehling-Uhlenbeck model calculations incorporating the photon production channel from np process in which the HMTs of nucleons is considered. A non-zero HMT ratio of about 15% is favored by the data. The effect of the capture channel np→dγ is demonstrated.

The slurry erosion processes of horizontal elbows are investigated numerically using an Eulerian-Lagrangian method coupled with particle rebound and erosion model. First, a mechanical model for the internal multiphase flow involving slurry erosion in the 90° horizontal elbow is established and the corresponding governing equations are presented. Then, a two-way coupled numerical solution procedure is developed and its accuracy and stability are examined carefully using benchmark pipe flow models with experimental results. Using the validated numerical methods, the effects of flow velocity, fluid density and fluid viscosity on the flow and slurry erosion in the horizontal elbow are analyzed in detail. Finally, a prediction method of erosion rate distribution based on the pipe Froude number, particle Stokes number and the Dean number is proposed. In this method the pipe Froude number is employed to qualify the effect of ununiform distribution of particles, particle Stokes number and Dean number are combined to qualify the effects of inertia force, drag force and secondary flow. Using this approach, the location of the maximum erosion rate in horizontal elbows under different operating conditions can be predicted more conveniently.

IntroductionA potential association between periodontitis and endometriosis has been indicated in previous observational studies. Nevertheless, the causal link between these two disorders has not been clarified.MethodsBased on publicly available genome-wide association study (GWAS) summary datasets, we conducted a bidirectional Mendelian randomization (MR) study to investigate the relationship between periodontitis and endometriosis and its subtypes. Single nucleotide polymorphisms (SNPs) strongly associated with candidate exposures at the genome-wide significance level (P < 5 × 10−8) were selected as instrumental variables (IVs). The inverse variance-weighted regression (IVW) was performed to estimate the causal effect of periodontitis on endometriosis. We further conducted two sensitivity analyses, MR-Egger and weighted median, to test the validity of our findings. The main results were replicated via data from the UK Biobank. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causality.ResultsThe IVW method suggested that periodontitis was positively associated with endometriosis of the pelvic peritoneum (OR = 1.079, 95% CI = 1.016 to 1.146, P = 0.014). No causal association was indicated between periodontitis and other subtypes of endometriosis. In reversed analyses, no causal association between endometriosis or its subtypes and periodontitis was found.ConclusionsOur study provided genetic evidence on the causal relationship between periodontitis and endometriosis of the pelvic peritoneum. More studies are necessary to explore the underlying mechanisms.

Introduction: As signal molecules in aerobic organisms, locally accumulated ROS have been reported to balance cell division and differentiation in the root meristem. Protein posttranslational modifications such as lysine acetylation play critical roles in controlling a variety of cellular processes. However, the mechanism by which ROS regulate root development is unknown. In addition, how protein lysine acetylation is regulated and whether cellular ROS levels affect protein lysine acetylation remain unclear. Objectives: We aimed to elucidate the relationship between ROS and protein acetylation by exploring a rice mutant plant that displays a decreased level of ROS in postembryonic crown root (CR) cells and severe defects in CR development. Methods: First, proteomic analysis was used to find candidate proteins responsible for the decrease of ROS detected in the wox11 mutant. Then, biochemical, molecular, and genetic analyses were used to study WOX11-regulated genes involved in ROS homeostasis. Finally, acetylproteomic analysis of wild type and wox11 roots treated with or without potassium iodide (KI) and hydrogen peroxide (H2O2) was used to study the effects of ROS on protein acetylation in rice CR cells. Results: We demonstrated that WOX11 was required to maintain ROS homeostasis by upregulating peroxidase genes in the crown root meristem. Acetylproteomic analysis revealed that WOX11-dependent hydrogen peroxide (H2O2) levels in CR cells promoted lysine acetylation of many non-histone proteins enriched for nitrogen metabolism and peptide/protein synthesis pathways. Further analysis revealed that the redox state affected histone deacetylases (HDACs) activity, which was likely related to the high levels of protein lysine acetylation in CR cells. Conclusion: WOX11-controlled ROS level in CR meristem cells is required for protein lysine acetylation which represents a mechanism of ROS-promoted CR development in rice.

In-situ photocatalytic H2O2 production has been receiving increasing attention in recent years for sustainable H2O2 synthesis. Graphitic carbon nitride (g-C3N4) is regarded as one of the most promising semiconductor photocatalysts for H2O2 evolution. Introducing N defects in g-C3N4 has been proved to be an effective strategy to enhance photocatalytic activity. However, the photocatalytic mechanism of the N vacancies is ambiguous and different types of N vacancies in g-C3N4 may exhibit different effects on photocatalytic activity. Herein, we develop a facile sodium persulfate eutectic polymerization method to prepare the g-C3N4 with abundant three coordinate nitrogen (N3C) vacancies. This type of nitrogen vacancy has not been studied in g-C3N4 for photocatalytic H2O2 production. Our results show that the introduction of N3C vacancies in the g-C3N4 successfully broadens the light absorption range, and inhibits the photoexcited charge recombination with enhanced O2 adsorption to promote oxygen activation. The photocatalytic H2O2 evolution from the N3C-rich g-C3N4 is 4.5 times higher than that of the pristine g-C3N4. This study demonstrates a novel strategy to introduce N3C vacancies in g-C3N4, which offers a new method to develop active catalysts for photocatalytic H2O2 evolution.

Based on the Weather Research and Forecasting Model Coupled with Chemistry (WRF-Chem) atmospheric chemistry model, a parameterization scheme for the radioactive isotope caesium (137Cs), considering processes such as advection, turbulent diffusion, dry deposition, and wet deposition, was constructed, enabling the spatial distribution simulation of the concentration and deposition of 137Cs. The experimental simulation studies were carried out during the high emission period of the Fukushima nuclear accident (from 11 to 17 March 2011). Two sets of comparison experiments, with or without deposition, were designed, the effects of wind field and precipitation on the spatial transport and ground deposition of 137Cs were analyzed, and the influence of wind field and precipitation on 137Cs vertical transport was analyzed in detail. The results indicate that the model can accurately simulate the meteorological and 137Cs variables. On 15 March, 137Cs dispersed towards the Kanto Plain in Japan under the influence of northeastern winds. In comparison to the experiment without deposition, the concentration of 137Cs in the Fukushima area decreased by approximately 286 Bq·m−3 in the deposition experiment. Under the influence of updrafts in the non-deposition experiment, a 137Cs cloud spread upward to a maximum height of 6 km, whereas in the deposition experiment, the highest dispersion of the 137Cs cloud only reach a height of 4 km. Affected by the wind field, dry deposition is mainly distributed in Fukushima, the Kanto Plain, and their eastern ocean areas, with a maximum dry deposition of 5004.5 kBq·m−2. Wet deposition is mainly influenced by the wind field and precipitation, distributed in the surrounding areas of Fukushima, with a maximum wet deposition of 725.3 kBq·m−2. The single-station test results from the deposition experiment were better than those for the non-deposition experiment: the percentage deviations of the Tokyo, Chiba, Maebashi, and Naraha stations decreased by 61%, 69%, 46%, and 51%, respectively, and the percentage root mean square error decreased by 46%, 25%, 38%, and 48%, respectively.

Hydrocolloids, as thickeners, have been receiving increasing attention from researchers. Although they exhibit significant free radical quenching abilities, which demonstrate potential heterocyclic amines (HAs) inhibitory capabilities by blocking the free radical pathway, the inhibitory effect and mechanism are still unclear. This study investigated the effects of three typical hydrocolloids (alginic acid, chitosan, and carrageenan) on both free and bound HAs in fried meatballs, along with their mechanisms of free radical quenching using density functional theory. The result showed that all three hydrocolloids can effectively inhibit the generation of HAs. The maximum inhibition rate reached 33.33% for free HAs and 23.18% for bound HAs. Phenylacetaldehyde, glyoxal and methyl glyoxal, were significantly inhibited, indicating that hydrocolloids alleviated the production of HAs by inhibiting the generation of intermediates. At moment, three hydrocolloids effectively inhibited the generation of total free radicals. Frontier orbital and density functional theory analysis revealed that carrageenan had the lowest HOMO-LUMO energy gaps, ionization potential, highest nucleophilic index, chemical potential, and was more likely to react with free radicals. The results of this study indicate that three hydrocolloids can effectively inhibit HAs and provide theoretical support for their applications in food processing and safety.

The extraction of species-specific calls from passive acoustic recordings is a common preliminary step in ecological analysis. But for many species, especially those occupying noisy, acoustically variable habitats, the call extraction process remains largely manual, a time-consuming, and increasingly unsustainable process. Deep neural networks have been shown to provide excellent performance in a range of acoustic classification applications. We take as an example the recognition of four songs of one of the rarest mammals in the world, the western black-crested gibbon (Nomascus concolors).The process of recognition in this paper which includes distributed BIC ambient sound segmentation based on the OpenPAI platform; DNN-based western black-crested gibbon song enhancement processing; data pre-processing, labeling samples; proposed DNN + ResNet34 + CBAM + GRU + Attention recognition model; comparing other classical neural network models.Our best model converts acoustic recordings into spectrogram images on the mel frequency scale and uses these images to train convolutional neural networks.Our proposed model proved to be very accurate in predicting the segmented western black-crested gibbon songs with an accuracy of 99.8%, and almost a few western black-crested gibbon songs were incorrectly identified when all segmented data were recognized. In the four consecutive years of the acoustic monitoring system deployed in the Ailao Mountain National Nature Reserve, the western black-crested gibbon was most active near the monitoring site from March to August each year, and least active in January and February. Based on call sound intensity analysis, we monitored a total of two different western black-crested gibbon groups (G1 and G2) during the monitoring cycle. We demonstrate that passive acoustic monitoring combined with CNN classifiers is an effective tool for the remote detection of one of the rarest and most threatened species in the world.

Coral sand is widely encountered in coastal areas of tropical and subtropical regions. Compared with silica sand, it usually exhibits weaker performance from the perspective of engineering geology. To improve the geomechanical performance of coral sand and meet the requirement of foundation construction in coastal areas, a novel alkali activation-based sustainable binder was developed. The alkali-activated slag (AAS) binder material was composed of ground granulated blast-furnace slag (GGBS) and hydrated lime with the amendment of biochar, an agricultural waste-derived material. The biochar-amended AAS stabilized coral sand was subjected to a series of laboratory tests to determine its mechanical, physicochemical, and microstructural characteristics. Results show that adding a moderate amount of biochar in AAS could improve soil strength, elastic modulus, and water holding capacity by up to 20%, 70%, and 30%, respectively. Moreover, the addition of biochar in AAS had a marginal effect on the sulfate resistance of the stabilized sand, especially at high biochar content. However, the resistance of the AAS stabilized sand to wet-dry cycles slightly deteriorated with the addition of biochar. Based on these observations, a conceptual model showing biochar-AAS-sand interactions was proposed, in which biochar served as an internal curing agent, micro-reinforcer, and mechanically weak point.

Abstract Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.

Calcareous sand is widely present in coastal areas around the world and is usually considered as a weak and unstable material due to its high compressibility and low strength. Microbial-induced calcium carbonate precipitation (MICP) is a promising technique for soil improvement. However, the commonly adopted bio-augmented MICP approach is in general less compatible with the natural soil environment. Thus, this study focuses on the bio-stimulated MICP approach, which is likely to enhance the dominance of ureolytic bacteria for longer period and thus is deemed more efficient. The main objective of this paper is to investigate the compressibility of calcareous sand treated by bio-stimulated MICP approach. In the current study, a series of one-dimension compression tests was conducted on bio-cemented sand prepared via bio-stimulation with different initial relative densities (Dr). Based on the obtained compression curves and particle size distribution (PSD) curves, the parameters including cementation content, the coefficient of compressibility (av), PSD, relative breakage (Br), and relative agglomeration (Ar) were discussed. The results showed that av decreased with the increasing cementation content. The bio-cemented sand prepared with higher initial Dr had smaller (approximately 20%–70%) av values than that with lower initial Dr. The specimen with higher initial Dr and higher cementation content resulted in smaller Br but larger Ar. Finally, a conceptual framework featuring multiple contact and damage modes was proposed.

The cells of colorectal cancer (CRC) in their microenvironment experience constant stress, leading to dysregulated activity in the tumor niche. As a result, cancer cells acquire alternative pathways in response to the changing microenvironment, posing significant challenges for the design of effective cancer treatment strategies. While computational studies on high-throughput omics data have advanced our understanding of CRC subtypes, characterizing the heterogeneity of this disease remains remarkably complex. Here, we present a novel computational Pipeline for Characterizing Alternative Mechanisms (PCAM) based on biclustering to gain a more detailed understanding of cancer heterogeneity. Our application of PCAM to large-scale CRC transcriptomics datasets suggests that PCAM can generate a wealth of information leading to new biological understanding and predictive markers of alternative mechanisms. Our key findings include: 1) A comprehensive collection of alternative pathways in CRC, associated with biological and clinical factors. 2) Full annotation of detected alternative mechanisms, including their enrichment in known pathways and associations with various clinical outcomes. 3) A mechanistic relationship between known clinical subtypes and outcomes on a consensus map, visualized by the presence of alternative mechanisms. 4) Several potential novel alternative drug resistance mechanisms for Oxaliplatin, 5-Fluorouracil, and FOLFOX, some of which were validated on independent datasets. We believe that gaining a deeper understanding of alternative mechanisms is a critical step towards characterizing the heterogeneity of CRC. The hypotheses generated by PCAM, along with the comprehensive collection of biologically and clinically associated alternative pathways in CRC, could provide valuable insights into the underlying mechanisms driving cancer progression and drug resistance, which could aid in the development of more effective cancer therapies and guide experimental design towards more targeted and personalized treatment strategies. The computational pipeline of PCAM is available in GitHub (https://github.com/changwn/BC-CRC).

Dual active bridge (DAB) converters are extensively used due to the advantages of wide voltage regulation range and easy realization of soft switching. Besides, the concept of partial power converters (PPCs) has been widely applied to increase the converter efficiency by reducing the power actually processed by the converter. Therefore, in this article, the DAB converter and PPC are combined. And a high frequency DAB-based PPC aiming at efficiency optimization is selected out by analyzing and comparing the characteristics of several connections. Considering the wide voltage regulation range of DAB-based PPC, the extended-phase-shift-based control strategy aiming at zero-voltage switching (ZVS) range and current stress optimization is analyzed and adopted in this article. With the trend of high frequency for power converters, the non-ideal factors like output capacitors of switches need to be considered to improve the performance. The output capacitors are taken into consideration when analyzing the ZVS performance and the magnetizing inductor is utilized to expand ZVS range. To verify correctness of theoretical analysis, a prototype using GaN devices with 1 kW rated output power and 500 kHz switching frequency is built. The experimental results are consistent with the analysis.

Abstract Transcription activator-like effectors (TALEs) are proteins produced by plant pathogenic Xanthomonas spp. TALEs exhibit a conserved structure and have the ability to directly bind to the promoter region of host target genes where they activate transcription. TALEs in Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight (BB) in rice, play important roles in triggering resistance (ETI) and susceptibility (ETS) for rice immunity. This review briefly describes rice resistance breeding in China, TALE properties and their roles, BB resistance (R) and susceptibility (S) genes in rice, the arms-race between TALEs and TALE-targets, and strategies for breeding disease-resistant crops. A systematic overview of the complex roles of TALEs are presented along with ongoing efforts to breed crops with durable and broad-spectrum resistance to the pathogenic bacterium.

Abstract Folate (vitamin B9) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 remains unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5–3.6 Å resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work establishes the molecular basis of substrate recognition by this central folate transporter.