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Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract The release and escape of radioactive materials has posed tremendous threats to the global environment. Among various radioactive elements, 90Sr has attracted growing attention due to its long half-life and its tendency to accumulate in bone tissue. Nonetheless, the concentration of 90Sr in radioactive waste is exceedingly low, far below the detection limits of currently available strontium-targeting chemical sensors. Herein, we propose an optical nanosensor (Sr2+-nanosensor) that exhibits an ultra-low detection limit of 0.5 nM, surpassing the 90Sr in the treated radioactive water from the Fukushima. The sensor offers wide sensing range of eight orders of magnitude, rapid response of less than 10 s, and high selectivity against 31 common ions. These excellent performances are attributed to a specific ligand (Sr2+-ligand) for Sr2+ recognition. The Sr2+ is found to be bound by six oxygen atoms from the Sr2+-ligand with a stability constant at least two orders higher than that of other traditional ligands. This study offers invaluable insights for the design of Sr2+-sensing methodologies as well as a technique for detecting trace amounts of environmental radioactive pollution.

Abstract The concept of sustainable development has led to a growing research interest in bio-based flame-retardant polyurethane foams. These foams offer environmentally friendly, sustainable, and flame-retardant raw materials for the construction, automotive, and furniture industries. The 15 wt% soybean oil-based polyol rigid polyurethane foams (RPUF-S3A20B system) were modified with 20 wt% ammonium polyphosphate (APP) and homemade magnesium borate hydroxide (MgBO2(OH)). Thermogravimetric analysis, pyrolysis kinetic analysis, limiting oxygen index (LOI) test, cone calorimetry (CONE), morphological analysis, and smoke density (Ds) were employed to investigate the impact of MgBO2(OH) on the thermal stability and flame-retardant properties of the RPUF-S3A20B system. The results indicated that RPUF-S3A20B12.5 with 12.5 wt% MgBO2(OH) had better thermal stability and higher activation energy. In addition, its LOI was increased by 3.1% compared to RPUF-S3A20 without MgBO2(OH). The peak heat release rate (PHRR) and total heat release rate (THR) of RPUF-S3A20B12.5 at a radiant flux of 25 kW/m2 were reduced by 45.8% and 35.0% compared with RPUF-S3A20. RPUF-S3A20B12.5 demonstrated the lowest smoke density (17.4 and 17.5) and highest light transmission (73.9% and 73.7%) in both flameless and flame conditions, indicating superior flame-retardant and smoke-suppression properties. These findings offered valuable insights for further research on synergistic flame-retardant systems in bio-based polyurethane foams.

Abstract Background Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. Methods Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. Results A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. Conclusions This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Abstract Maintaining food safety and quality is critical for public health and food security. Conventional food preservation methods, such as pasteurization and dehydration, often change the overall organoleptic quality of the food products. Herein, we demonstrate a method that affects only a thin surface layer of the food, using beef as a model. In this method, Joule heating is generated by applying high electric power to a carbon substrate in ~2000 K. The beef surface in direct contact with the heating substrate is subjected to ultra-high temperature flash heating, leading to the formation of a microbe-inactivated, dehydrated layer of ~100 µm in thickness. Aerobic mesophilic bacteria, Enterobacteriaceae, yeast and mold on the treated samples are inactivated to a level below the detection limit and remained low during room temperature storage of 5 days. Meanwhile, the product quality, including visual appearance, texture, and nutrient level of the beef, remains mostly unchanged. In contrast, microorganisms grow rapidly on the untreated control samples, along with a rapid deterioration of the meat quality. This method might serve as a promising preservation technology for securing food safety and quality.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Studying rice water requirements (ETc) and area is crucial for developing irrigation schedules and adjusting crop structures. The cold rice cultivation region is China’s main high-quality rice production base and has the lowest temperature, highest latitude, and greatest sensitivity to climate. However, little research has focused on its past rice distributions and ETc, and its future variations are not yet clear. Past ETc was calculated by the Penman–Monteith and crop-corrected coefficient method, and past rice distribution patterns were analyzed based on the annual paddy rice planting area datasets. Future reference crop evapotranspiration (ET0) was projected by the statistical downscaling model (SDSM) based on the CMIP6 ensemble of daily predictor variables. The food and agriculture projections to 2050 datasets were used to project future rice areas, and the patch-generating land use simulation (PLUS) model simulated rice distribution. Finally, we projected future rice water supply demand. The results showed that ETc showed a decreasing trend, and the total rice area and production increased by 4.52 and 5.49 times from 1990 to 2020. Both in the past and future, rice was densely distributed in and expanded into the Sanjiang and Songnen Plains, and the spatial characteristic of ETc was as follows: the west was larger than the east, the north was larger than the south, and the central was in between. In the four future periods, the total ETc demonstrated an upward trend, increasing by 7.44–21.04, 15.64–34.74, 24.74–45.84, and 16.14–41.14 mm under the SSP126, SSP245, SSP370, and SSP585 scenarios, respectively, compared to the historical period. And it is generally ranked as SSP370 > SSP245 > SSP126. Finally, we projected future rice water supply meet the demand caused by rice area expansion.

Purpose: To investigate the factors influencing hypothermia during pancreaticoduodenectomy and establish and verify a prediction model. Method: The clinical data of patients undergoing pancreaticoduodenectomy in Hunan People's Hospital between January 1, 2022 and October 15, 2022 were analysed. The patients were divided into a hypothermia group (n = 302) and a non-hypothermia group (n = 164) according to whether hypothermia occurred during surgery. A binary logistic regression model was used to analyse the independent risk factors for hypothermia in patients undergoing pancreaticoduodenectomy. A risk prediction model was established, and R software was used to plot a column graph. The predictive value of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: Among the 466 patients undergoing pancreaticoduodenectomy, 302 (64.81 %) had hypothermia, including 154 men and 148 women, with a median age of 58.6 (38–86) years. The binary logistic regression analysis showed that low body mass index (BMI), room temperature at the time of entry, intraoperative flushing fluid volume and peritoneal flushing fluid temperature were independent risk factors for intraoperative hypothermia in patients undergoing pancreaticoduodenal surgery (P

Amorphophallus spp. is an important group of crop and medicinal plants, but it is susceptible to infection by soft rot disease during both field growth and storage stages. This results in huge economic and yield losses, which must be properly addressed. Combined applications of Biological Control Agents (BCAs) and compatible chemicals have been recently considered as a more effective and reliable method to control bacterial soft rot. In the present study, we investigated the control effects against soft rot pathogenic bacteria Pectobacterium aroidearum MY11, using a BCA strain (i.e. Bacillus velezensis BCP6) and screening for three different bactericides, i.e. Jinggangmycin (JGM), Thiodiazole copper and Qingkulike. After exploring a joint application of BCP6 with chemicals, we found that JGM was the most effective and compatible bactericide to be compounded with BCP6. First, in the in vitro experiment, the mixture of JGM (34 mg/L) and suspension of BCP6 (1.0 × 108 cfu/mL) at 4:6 volume ratio performed with the strongest inhibitory effect on P. aroidearum MY11 (53.40%) and synergistic effect (1.78); this combination also significantly increased the biofilm production by BCP6, and constrained the swimming motility of P. aroidearum MY11 in agar plates and inhibited activities of cell wall-degrading enzymes. Second, the combined application of JGM and BPC6 reached up to 95.81% of control efficacy against P. aroidearum MY11 in a greenhouse experiment, and compared to JGM or BCP6 alone, combined application effectively increased konjac plant resistance to soft rot in the field, showing a synergistic action. Collectively, these results provided an alternative method for the management of soft rot disease in konjac planting.

A Generative Adversarial Network (GAN) based asphalt pavement crack image generation method was proposed to improve the dataset size of the road images. Five open-source road crack datasets were leveraged to construct an image dataset, which contained two labels - transverse cracks and longitudinal cracks. The constructed dataset was used to facilitate crack detection and classification research by providing a diverse collection of labeled crack images derived from multiple public sources. The network structure of fully connected, convolutional and attention mechanisms based on the Conditional Generative Adversarial Network (CGAN) was used in this project. The purpose of this study was to train a generative model on selected categories of input pavement crack images and generate realistic crack images of those categories. We aim to tune the parameters of the GAN and optimize hyperparameters to improve the realism possibility of generated images. It also explored the generated images with different sizes and evaluated the performance of networks with different architectures. In particular, we analyzed the structural characteristics of conditional GAN. Results demonstrated that the Self-Attention Generative Adversarial Networks (SAGAN) model, which combines self-attention mechanisms with CGAN, can effectively address challenges related to limited crack image data and the inability to selectively generate images from specific categories. By conditioning the generator on category information, the SAGAN model was able to generate high-quality images while focusing on the target categories. Overall, the self-attention and conditional aspects of the SAGAN framework helped improve the generation of realistic pavement crack images.

Abstract The voltage source converter (VSC) interlinking AC and DC power networks is a core equipment in AC/DC hybrid power systems. To analyze the stability of this system based on the impedance method, it is necessary to establish the hybrid AC/DC admittance model of interlinking VSC. This paper presents a unified and systematic AC/DC hybrid admittance modelling framework which is widely applicable to different control methods of interlinking VSCs. The hybrid admittance models for interlinking VSCs under PQ control, VdcIq control, and Vf control are explicitly formulated, with their elements individually reflecting the dynamics of the AC side, DC side, and the interaction between them. Subsequently, the impedance network model of interlinking VSC systems is formulated based on the hybrid admittance, and furthermore the frequency‐domain modal analysis is performed to analyze the system oscillation stability. Finally, frequency scanning and time‐domain simulation results in MATLAB/Simulink are provided to validate the effectiveness of the modelling and oscillation stability analysis method.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Since the onset of the SARS-CoV-2 pandemic in early 2020, there has been a notable rise in sodium hypochlorite disinfectants. Sodium hypochlorite undergoes hydrolysis to generate hypochlorous acid for virus eradication. This chlorine-based disinfectant is widely utilized for public disinfection due to its effectiveness. Although sodium hypochlorite disinfection is convenient, its excessive and indiscriminate use can harm the water environment and pose a risk to human health. Hypochlorous acid, a reactive oxygen species, plays a crucial role in the troposphere, stratospheric chemistry, and oxidizing capacity. Additionally, hypochlorous acid is vital as a reactive oxygen species in biological systems, and its irregular metabolism and level is associated with several illnesses. Thus, it is crucial to identify hypochlorous acid to comprehend its environmental and biological functions precisely. Here, we constructed a new fluorescent probe, utilizing the twisted intramolecular charge transfer mechanism to quickly and accurately detect hypochlorous acid in environmental water and biosystems. The probe showed a notable increase in fluorescence when exposed to hypochlorous acid, demonstrating its excellent selectivity, fast response time (less than 10 seconds), a large Stokes shift (∼ 102 nm), and a low detection limit of 15.5 nM.

BackgroundTo explore the clinical characteristics, etiological factors, and clinical-related genetic variant of children with acute necrotizing encephalopathy (ANE) related to the Omicron BF.7.14 novel coronavirus.MethodsGenomic variations were detected through whole exome sequencing. Additionally, we summarized the clinical data to explore the inheritance patterns associated with novel coronavirus-related ANE.ResultsThis study included four patients (2 males and 2 females) with an average age of 2.78 ± 1.93 years. All the patients had prodromal symptoms of Omicron BF.7.14 virus infection, and exhibited symptoms such as altered consciousness, seizures and cognitive/language disturbances. Cranial MRI scans revealed damage to the thalamus, basal ganglia and brainstem. The cerebrospinal fluid (CSF) cell counts were nearly normal, but protein level in CSF increased significantly. Genetic analysis revealed a novel truncated variant of CRMP2 gene in one patient who suffered more severe coma score and prognosis and dead in the later stages. All children exhibited a decrease in the absolute count of T lymphocytes, helper T cells, suppressor T cells, and NK cells to varying degrees. Furthermore, levels of cytokines, including IL-1 β, IL-5, IL-6 and IL-8 were significantly elevated in the CSF, especially in patient with truncated variant of CRMP2 gene.ConclusionThe Omicron BF.7.14 type novel coronavirus can lead to ANE, characterized by T cell immunosuppression and a significant increase in cytokine levels in the CSF. The truncated variation of CRMP2 gene may affect the prognosis of ANE by affecting the migration of cerebral T cells.

Cancer remains a major cause of death globally. Esophageal cancer is one of the most aggressive malignancies and has limited treatment options, thus resulting in high morbidity and mortality. We reported the case of a 65-year-old patient who came to the hospital for abdominal distension and loss of appetite. The patient’s endoscopy before admission indicated the possibility of esophageal cancer. After admission, an enhanced c omputed t omography (CT) scan of the chest and abdomen revealed esophageal stenosis and a liver tumor. The patient’s final diagnosis was esophageal cancer concurrent with liver cancer, and a series of treatments were administered. However, esophageal cancer with liver cancer is rare. The patient was treated with targeted therapy, immunotherapy, and transcatheter arterial chemoembolization simultaneously. Then, regular follow-up was performed at 1 month, and at 3 months, the patient was discharged after immunotherapy. We hope that through this case, we can improve the clinical understanding of these two types of tumors and thereby contribute to their treatment. Research and collaboration among health-care professionals are essential for improving tumor diagnosis and treatment.

Abstract To evaluate the role of focal cortical dysplasia co‐localization to cortical functional networks in the development of pharmacoresistance. One hundred thirty‐six focal cortical dysplasia patients with 3.0 T or 1.5 T MRI were identified from clinical databases at Children's National Hospital. Clinico‐radio‐pathologic factors and network co‐localization were determined. Using binomial logistic regression, limbic network co‐localization (odds ratio 4.164 95% confidence interval 1.02–17.08, p = 0.048), and focal to bilateral tonic–clonic seizures (4.82, 1.30–18.03, p = 0.019) predicted pharmacoresistance. These findings provide clinicians with markers to identify patients with focal cortical dysplasia‐related epilepsy at high risk of developing pharmacoresistance and should facilitate earlier epilepsy surgical evaluation.

Ammonium polyphosphate (APP) and self-made nickel phytate (PANi) were used as modified materials to prepare green biomass rigid polyurethane foam (RPUF). The flame retardancy, thermal stability, smoke toxicity and mechanical properties of the modified RPUF were investigated by limiting oxygen index (LOI), a cone calorimetry (CONE) test, thermogravimetric analysis and a compression test. The results showed that the RPUF with 10 wt% APP (PANi/APP10) had the highest LOI of 26.5%. Its peak heat release rate (PHRR) and total heat release (THR) were reduced by 29.64% and 24.05% compared with PANi/APP0 without APP. And its smoke production rate (SPR) and total smoke release (TSR) decreased by 33.14% and 19.88%, respectively. Compared with pure RPUF, the compressive strength of PANi/APP10 was increased by 50%, mainly because APP itself was an ultra-fine powder, which was better compatible with the matrix and improved the hardness of the material. The results showed that the synergistic effect of the gas phase and the condensed phase mechanism could effectively improve the flame-retardant effect. The current research results provided a new strategy for the preparation of green and low-toxicity RPUF.

ABSTRACTPeriodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high S. cristatus-P. gingivalis ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high S. cristatus-P. gingivalis ratio groups. Notably, a higher microbial diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios. It, therefore, indicates that the S. cristatus-P. gingivalis ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the S. cristatus-P. gingivalis ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.IMPORTANCEPeriodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although Porphyromonas gingivalis is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of Streptococcus cristatus and the ratios of S. cristatus and P. gingivalis in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against P. gingivalis and improving the efficiency of periodontal treatments.

BackgroundBracing is an essential part of scoliosis treatment. The standard of brace treatment for patients with scoliosis today is still very variable in terms of brace quality and outcome. The Gensingen brace is a further developed Chêneau brace derivative with individual design, which can be adapted through computer-aided design. ObjectiveThis study aims to generate a template to obtain a database for prospective multicenter studies study to analyze the results of high-corrective asymmetric Gensingen brace treatment for patients with adolescent idiopathic scoliosis (AIS). MethodsA template for the database was created, which contains the patients' basic data (age, menarcheal status, Risser Sign, curve pattern, and daily brace wearing time), the Cobb angles of curvature, and the cosmetically relevant angles of trunk rotation (ATR). A retrospective review of medical records of patients with AIS, who met the Scoliosis Research Society’s inclusion criteria for brace studies, was performed to test the feasibility of the template. Template items were filled in by the researchers. ResultsOut of 115 patients between 2014 and 2018, the complete data of 33 patients followed up at least 3 months after complete Gensingen brace weaning could be analyzed. The mean age was 12 years, the mean Cobb angle was 33.6°, and the mean Risser value was 0.7 at the beginning of the treatment. The mean improvement in the Cobb angle on in-brace x-ray imaging was –26.1० (80% of in-brace correction). The Cobb angle of the major curvature changed as follows: curve stabilization was achieved in 7 (21.2%) cases, and curve improvement was achieved in 26 (78.8%) cases. None of the patients showed a curve progression. The Cobb angle was significantly reduced in the brace at the end of treatment and at follow-up evaluation (P

PurposeDespite strong efforts to promote human papillomavirus (HPV) vaccine and cervical cancer screening, cervical cancer remains a threat to women’s reproductive health. Some high-risk HPV types play a crucial role in the progression of cervical cancer and precancerous lesions. Therefore, HPV screening has become an important means to prevent, diagnose, and triage cervical cancer. This study aims to leverage artificial intelligence to predict individual risks of cervical intraepithelial neoplasia (CIN) in women with high-risk HPV infection and to recommend the appropriate triage strategy and follow-up period according to the risk level.Materials and methodsA total of 475 cases were collected in this study. The sources were from the Department of Gynecology and Obstetrics in a tertiary hospital, a case report on HPV from the PubMed website, and clinical data of cervical cancer patients from The Cancer Genome Atlas (TCGA) database. Through in-depth study of the interaction between high-risk HPV and its risk factors, the risk factor relationship diagram structure was constructed. A Classification of Lesion Stages (CLS) algorithm was designed to predict cervical lesion stages. The risk levels of patients were analyzed based on all risk factors, and follow-up periods were formulated for each risk level.ResultsOur proposed CLS algorithm predicted the probability of occurrence of CIN3—the precancerous lesion stage of cervical cancer. This prediction was based on patients’ HPV-16 and -18 infection status, age, presence of persistent infection, and HPV type. Follow-up periods of 3–6 months, 6–12 months, and 3- to 5-year intervals were suggested for high-risk, medium-risk, and low-risk patients, respectively.ConclusionA lesion prediction model was constructed to determine the probabilities of occurrence of CIN by analyzing individual data, such as patient lifestyle, physical assessments, and patient complaints, in order to identify high-risk patients. Furthermore, the potential implications of the calculated features were mined to devise prevention strategies.

Abstract The maximum supersaturation (Sx) in clouds is a key parameter affecting the cloud's microphysical and radiative properties. We investigate the Sx of the marine boundary layer clouds by combining airborne and surface observations in the Eastern North Atlantic. The cloud droplet number concentration (Nc) in the least diluted cloud cores agrees well with the number concentration of particles larger than the Hoppel Minimum (HM) (N>HM) below clouds, indicating that the HM represents the average size threshold above which particles are activated to form cloud droplets. The Sx values derived from surface observations vary from 0.10% to 0.50% from June 2017 to June 2018, with a clear seasonal variation exhibiting higher values during winter. Most of the Sx variance (∼60%) can be explained by the cloud condensation nuclei (CCN) concentration and updraft velocity (w), with the CCN concentration playing a more important role than w in explaining the variation of Sx. The influence of CCN concentration on Sx leads to a buffered response of Nc to aerosol perturbations. The response of Nc to low aerosol concentration during winter is further buffered by the high w. The global Community Earth System Model (CESM) simulated Sx values in the Azores have a positive bias compared to measured Sx, likely due to overestimated w and underestimated CCN concentration. The CESM simulated Sx exhibits higher values further north over the North Atlantic Ocean, which is attributed to stronger w. The suppression of Sx by aerosol is also evident in regions with high CCN concentrations.

Study region: This research studies Sanjiang Plain because of its past drastic climate change and paddy area expansion, and future paddy area continue to expand supported by water conservancy project. Study focus: This research focuses on projecting high-resolution reference crop evapotranspiration (ETo) spatiotemporal variation under future climate and underlying surface change, and quantified its coupled effects. New hydrological insights for the region: The integrated framework of Patch-generating Land Use Simulation, Weather Research and Forecasting, and bias-corrected CMIP6 dataset is proposed to consider the integration of future paddy area expansion and climate change impacts on ETo. Results showed that future paddy area will continue to increase, but it is much lower than past expansion scale. The average temperature, average relative humidity, and total ETo show an increasing trend. The spatial distribution is characterized by temperature and ETo reaches its highest value in central region, and decreases along the surrounding area, but relative humidity is diametrically opposed. The central regions have significant change in temperature, relative humidity, and ETo, deserving further attention. The coupled effect of paddy expansion and climate change is reflected in increasing average temperature (0.95–1.94 °C) and total ETo (19–39.96 mm), but decreasing average wind speed (0.09–0.12 m/s).

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.

OBJECTIVES/GOALS: Childhood psychopathology is a worsening public health crisis leading to negative life outcomes, including self-harm and suicide. Difficulty in self-control as early as 3 years old predicts psychopathology, but the mediating mechanisms of brain function are unknown. Here, we tested one mechanism: functional connectivity (FC) integration. METHODS/STUDY POPULATION: We studied a sample of 204 children [53 F/149 M/2 NC; mean age (SD)=11 years (1.7)] with diverse self-control difficulties (e.g., attention deficit disorder [n=80]; autism spectrum disorders [n=91]). We extracted a general factor of psychopathology (“p-factor”) from the parent-reported Child Behavior Checklist. For participants with high quality fMRI data on 3 self-control tasks (n=79), testing flexibility, working memory, and inhibition, we calculated FC connectomes reflecting a general self-control state, and applied connectome predictive modeling (CPM) to reveal connections predicting overall task impairment. We then measured individual variance in cross-network integration of regions with the most predictive connections and tested for association with p-factor in a multiple linear regression. RESULTS/ANTICIPATED RESULTS: We repeated CPM 1,000 times with 10-fold cross validation to generate a distribution of accuracies for predicted vs. observed task impairment scores (mean r=0.25, permutation p=0.02). Connections selected a maximum of 10,000 times (10 folds * 1,000 repetitions) were strongly predictive of task impairment (r=-0.5, p

Radiation–induced enteritis is an unavoidable complication associated with pelvic tumor radiotherapy, significantly influencing the prognosis of cancer patients. The limited availability of commercial gastrointestinal radioprotectors in clinical settings poses a substantial challenge in preventing radiation enteritis. Despite the inherent radioprotective characteristics of Cur in vitro, its poor solubility in water, instability, and low bioavailability lead to inferior therapeutic effects in vivo. Herein, we developed novel ROS-responsive micelles (CTI) from inulin and curcumin, aimed at mitigating radiation enteritis. CTI micelles had excellent solubility and stability. Importantly, CTI improved the cytotoxicity and bioavailability of curcumin, thereby showing enhanced effectiveness in neutralizing ROS induced by radiation, safeguarding against DNA damage, and reducing radiation-induced cellular mortality. Moreover, in a radiation enteritis mice model, CTI not only alleviated severe radiation-induced intestinal injury but also improved redox-related indicators and reduced inflammatory cytokine expression. Furthermore, CTI effectively increased gut microbiota abundance and maintained gut homeostasis. In conclusion, CTI could be a promising candidate for the clinical management of radiation enteritis. Our study provides a new perspective for radioprotection using natural antioxidants.

Abstract Low-carbon city construction is one of the key issues that must be addressed for China to achieve high-quality economic development and meet the Sustainable Development Goals. This study creates a comprehensive evaluation index system of low-carbon city multivariate system based on carbon emission data from 30 typical Chinese cities from 2006 to 2017 and evaluates and analyzes the trend of city low-carbon levels using the CRITIC-TOPSIS technique and MK method. Meanwhile, the influence mechanism of the multi-coupled system is investigated using the coupling coordination degree model and random forest algorithm.The results show that there are 8 cities with a significant increasing trend of low-carbon level, 19 cities with no significant monotonic change trend, and 3 cities with a decreasing trend of low-carbon level. By analyzing the coupling coordination degree, we found that the coupling coordination degree between low-carbon level and economic development in most cities tends to increase year by year, from the initial antagonistic effect to a good coordination development trend, which confirms the “inverted U-shaped” relationship between economy and carbon emission. In addition, industrial pollutant emissions, foreign direct investment, and economic output are the core drivers of low-carbon levels in cities.

Abstract Background Hypochondroplasia (HCH) is a common nonlethal skeletal dysplasia caused by pathogenic variations in the fibroblast growth factor receptor 3 (FGFR3) gene, and HCH has similar clinical manifestations with achondroplasia (ACH), which can be screened during the fetal period by prenatal ultrasound testing and diagnosed by genetic testing. Case presentation we report the special case of a patient with obvious growth retardation and rhizomelic disproportionate short stature, accompanied by other manifestations, including an enlarged head and short hands at 1 year old. However, several multiple color ultrasound exams identified shortened limbs ( 95th percentile) and a low nasal bridge in the fetal period. Due to the high incidence rate of ACH, genetic testing for the hotspot FGFR3 gene c.1138 g > A pathogenic variations was performed immediately in the third trimester. Unfortunately, the definitive diagnosis could not be made before birth due to the negative result of hotspot gene exam. Whole exome sequencing (WES) was performed at 1 year identified FGFR3 gene c.1620C > A variations positivity, and the patient was finally diagnosed as HCH. Conclusion Our report extends the understanding of the limitations of prenatal genetic diagnostic testing, especially the hot spot pathogenic variations test should be not the only clinical diagnostic basis. Moreover, this case also emphasizes that further gene analysis for patients with significant conflict between the clinical manifestation and the prenatal genetic panel examination findings should be reconducted timely to spare the family from a delayed diagnosis or a misdiagnosis.

Abstract Background Isodicentric Y chromosome (idic(Y)) is the most commonly reported aberration of the human Y chromosome, which is an important cause of abnormal sexual development. The breakpoints of isodicentric Y chromosome mostly occurred in Yq11.2 and Yp11.3, however, the breakpoints in Yq12 are relatively rare. Case presentation We described a 10-year-old boy presenting hypospadias, micropenis and short stature, as well as unilateral cryptorchidism without normal testicular seminiferous tubules structure by biopsy. Whole exome sequencing didn’t find any pathogenic/likely pathogenic variants related to phenotypes of this patient. Copy number variation sequencing showed the duplication of whole Y chromosome. Subsequently, karyotyping and FISH analyses demonstrated his genetic diagnosis was mosaic 45,X[8]/46,X,psu idic(Y)(q12)[32], with the breakpoint in Yq12. Conclusions Our case proved that it would be beneficial to integrate high-throughput sequencing with cytogenetic technique for precise diagnosis, treatment and genetic counselling.

ABSTRACT Pectobacterium spp. are important bacterial pathogens that cause soft rot symptoms in various crops. However, their mechanism of pathogenicity requires clarity to help control their infections. Here, genome-wide association studies (GWAS) were conducted by integrating genomic data and measurements of two phenotypes (virulence and cellulase activity) for 120 various Pectobacterium strains in order to identify the genetic basis of their pathogenicity. An artificial intelligence-based software program was developed to automatically measure lesion areas on Chinese cabbage, thereby facilitating accurate and rapid data collection for virulence phenotypes for use in GWAS analysis. The analysis discovered 428 and 158 loci significantly associated with Pectobacterium virulence (lesion area) and cellulase activity, respectively. In addition, 1,229 and 586 epistasis loci pairs were identified for the virulence and cellulase activity phenotypes, respectively. Among them, the AraC transcriptional regulator exerted epistasis effects with another three nutrient transport-related genes in pairs contributing to the virulence phenotype, and their epistatic effects were experimentally confirmed for one pair with knockout mutants of each single gene and double gene. This study consequently provides valuable insights into the genetic mechanism underlying Pectobacterium spp. pathogenicity. Importance Plant diseases and pests are responsible for the loss of up to 40% of food crops, and annual economic losses caused by plant diseases reach more than $220 billion. Fighting against plant diseases requires an understanding of the pathogenic mechanisms of pathogens. This study adopted an advanced approach using population genomics integrated with virulence-related phenotype data to investigate the genetic basis of Pectobacterium spp., which causes serious crop losses worldwide. An automated software program based on artificial intelligence was developed to measure the virulence phenotype (lesion area), which greatly facilitated this research. The analysis predicted key genomic loci that were highly associated with virulence phenotypes, exhibited epistasis effects, and were further confirmed as critical for virulence with mutant gene deletion experiments. The present study provides new insights into the genetic determinants associated with Pectobacterium pathogenicity and provides a valuable new software resource that can be adapted to improve plant infection measurements.

Abstract An engineered bladder construct that mimics the structural and functional characteristics of native bladder is a promising therapeutic option for bladder substitution. We previously showed that pedicled vascularized smooth muscle tissue fabricated by grafting smooth muscle cell (SMC) sheets onto an axial capsule vascular bed had the potential for reliable bladder reconstruction. In this study, we investigated the feasibility of buccal mucosa graft (BMG) integration with the pedicled vascularized smooth muscle tissue to generate a full‐layer pedicled vascularized bladder construct. BMG transplanted onto vascularized smooth muscle tissue showed good survival and developed into a pedicled vascularized bladder construct with full‐layer structures, appropriate thickness, abundant vascularization, and effective barrier function. Then the full‐thickness bladder defects were, respectively, reconstructed by pedicled capsule tissue (pedicled capsule group), nonpedicled vascularized bladder construct (nonpedicled construct group), and pedicled vascularized bladder construct (pedicled construct group). The picrosirius red (PSR) staining and immunohistochemistry results showed minimal fibrosis, maximal smooth muscle proportion, and high vascular density in the pedicled construct group. A continuous mucosal layer was observed only in the pedicled construct group. Moreover, morphological and functional studies revealed better bladder compliance and good ductility in the pedicled construct group. Overall, these results suggested that the BMG could be well integrated with vascularized smooth muscle tissue and generated a pedicled, fully vascularized, and structurally organized bladder construct, which facilitated structural remodeling and functional recovery and could become an alternative to bladder reconstruction.

This study aimed to investigate the incidence of patent processus vaginalis (PPV) in pediatric patients with a unilateral nonpalpable testis and explore the associated factors. From May 2014 to April 2017, 152 boys who were diagnosed with a unilateral nonpalpable testis and underwent laparoscopy in Shanghai Children's Hospital (Shanghai, China) were included in this study. The data were collected and reviewed, and the results were analyzed regarding the age at operation, side, development, and position of the nonpalpable testis. The mean age of the patients was 2.6 (standard deviation: 2.3) years. The testis was absent in 14 cases, nonviable in 81 cases, and viable in 57 cases. The incidence of PPV was 37.5% (57 of 152) on the ipsilateral side and 16.4% (25 of 152) on the contralateral side. The ipsilateral PPV was more prevalent when the nonpalpable testis occurred on the right side (P < 0.01). Besides, patients with a viable testis had a greater incidence of ipsilateral PPV than those with a nonviable or absent testis (P < 0.01). Moreover, this rate was the highest when the testis was in the abdominal cavity and the lowest when the testis was in the scrotum (both P < 0.01). However, the incidence of contralateral PPV was independent of all the factors. In conclusion, in children with a nonpalpable testis, the incidence of an ipsilateral PPV was significantly related to the side, development, and position of the testis, while it was independent of these factors on the contralateral side.

TANK-binding kinase 1 (TBK1), a noncanonical member of the inhibitor-kappaB kinases (IKKs) family, plays a vital role in coordinating the signalling pathways of innate immunity, involving in the process of neuroinflammation, autophagy, and oncogenesis. In current study, based on rational drug design strategy, we discovered a series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent TBK1 inhibitors and dissected the structure–activity relationships (SARs). Through the several rounds of optimisation, compound 15y stood out as a potent inhibitor on TBK1 with an IC50 value of 0.2 nM and also displayed good selectivity. The mRNA detection of TBK1 downstream genes showed that compound 15y effectively inhibited TBK1 downstream IFN signalling in stimulated THP-1 and RAW264.7 cells. Meanwhile, compound 15y exhibited a micromolar antiproliferation effect on A172, U87MG, A375, A2058, and Panc0504 cell lines. Together, current results provided a promising TBK1 inhibitor 15y as lead compound for immune- and cancer-related drug discovery.

When detecting epikarst water using the self-potential method, the actual location of the anomaly center often deviates from the prospecting result due to the interference of the regional background field, which is comprised of geological noise and artificial electromagnetic fields. Ultimately, this makes it difficult to locate the detection target accurately. To address the potential offset of the anomaly center location, in this study we introduce the differential filtering method into the data processing procedure. This method has smoothing and low-pass filtering effects, facilitating the extraction of meaningful anomalies. Meanwhile, based on the anomalous features of different physical parameters, we propose an integrated method system based on differentially filtered horizontal self-potential gradient data, the composite profile method, and the high-density electrical method, which can effectively improve the accuracy of anomaly localization. This newly established method system was applied at the Xiaguantun test site in Longzhou County, Chongzuo, Guangxi Province, China, and its effectiveness and feasibility was confirmed.

ObjectivesPeriodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of Porphyromonas gingivalis and lower ratios of Streptococcus cristatus to P. gingivalis may contribute to periodontal health disparities. This prospective cohort study was designed to investigate if ethnic/racial groups responded differently to non-surgical periodontal treatment and if the treatment outcomes correlated to the bacterial distribution in patients with periodontitis before treatment.MethodsThis prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of P. gingivalis and S. cristatus was carried out using qPCR. Clinical parameters including probing depths and clinical attachment levels were determined before and after nonsurgical treatment. Data were analyzed using one-way ANOVA, the Kruskal–Wallis test, the paired samples t-test and the chi-square test.ResultsThe gains in clinical attachment levels after treatment significantly differed amongst the 3 groups–Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of P. gingivalis were highest in Hispanics, followed by African-Americans, and lowest in Caucasians (p = 0.015). However, no statistical differences were found in the numbers of S. cristatus amongst the 3 groups.ConclusionDifferential response to nonsurgical periodontal treatment and distribution of P. gingivalis are present in different ethnic/racial groups with periodontitis.

Abstract Medication and other therapies for psychiatric disorders show unsatisfying efficacy, in part due to the significant clinical/ biological heterogeneity within each disorder and our over-reliance on categorical clinical diagnoses. Alternatively, dimensional transdiagnostic studies have provided a promising pathway toward realizing personalized medicine and improved treatment outcomes. One factor that may influence response to psychiatric treatments is cognitive function, which is reflected in one’s intellectual capacity. Intellectual capacity is also reflected in the organization and structure of intrinsic brain networks. Using a large transdiagnostic cohort (n = 1721), we sought to discover neuroimaging biomarkers by developing a resting-state functional connectome-based prediction model for a key intellectual capacity measure, Full-Scale Intelligence Quotient (FSIQ), across the diagnostic spectrum. Our cross-validated model yielded an excellent prediction accuracy (r = 0.5573, p

Rice bean is an underexploited legume crop that has many desirable properties against bio and abiotic stresses. Here, the authors report the genome assembly of this species, conduct population genetics studies and reveal the genetic variations associated with adaptation and yield traits.

Abstract Background Hypospadias is a common congenital malformation in pediatric urology with surgery being the only curative treatment. Although there are hundreds of surgical methods for hypospadias, no single method can treat all types, and there are still high rates of postoperative complications. We performed this study to investigate surgical procedure selection and perform risk factor analysis of postoperative complications in hypospadias repair. Methods Retrospective analysis was performed of complete clinical and follow-up data of children with hypospadias who were treated and followed up at 15 children’s clinical centers in Mainland China from December 2018 to December 2019. Children were divided into groups according to Barcat classification and surgical methods in order to analyze the surgical choice for different types of hypospadias and the influencing factors of different surgical methods for complications. Results In total, 1011 patients were followed up for 26 months. According to Barcat classification, there were 248 cases of distal type hypospadias, 214 of intermediate, and 549 of proximal type. Transverse preputial island flap urethroplasty (Duckett) and tubularized incised plate urethroplasty (TIP) were performed in 375 (37.1%) and 336 cases (33.2%), respectively. The postoperative complication rate of distal hypospadias was 23.4% (15.8–57.1%), mid shaft 29.0% (22.7–40.0%), and proximal 43.7% (30.2–52.9%). Among the 375 patients in Duckett group, 192 had complications. Multivariate logistic analysis showed that the length of prepuce island flap (OR = 3.506, 95% CI: 2.258–5.442) was an independent risk factor for complications after Duckett operation (P

Abstract. Objective:. To investigate the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias. Methods:. We examined the overlap of genetically associated genes among NTDs, CHDs, and hypospadias. We then compared the expression profiles of these diseases based on all the detected genes and disease-associated TFs. The differentially expressed TFs that we obtained were further subjected to functional enrichment analysis to elucidate their role in the development of these birth defects. Results:. TF genes were significantly enriched in complex birth defects (P = 5.95 × 10−24). NTDs, CHDs, and hypospadias showed distinct gene expression profiles compared with the controls. Although TFs could not efficiently separate CHDs from normal subjects, distinct gene expression profiles of TFs could distinguish NTDs and hypospadias from controls. Differentially expressed TFs can be used to characterize NTDs, hypospadias, and controls. The enriched TFs in biological processes (BPs) reflected the different morphological processes of NTDs, CHDs, and hypospadias. Conclusions:. This study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through the related BPs. The investigation of genetically associated genes and gene expression profiles for the three different complex birth defects provides new insights into how the dysregulation of TFs influences their developmental process.

Summary: Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology is still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in the etiology of severe hypospadias, as these genes are related to androgen signaling. Additionally, rare damaging variants in cilia-related outer dynein arm heavy chain (ODNAH) genes (DNAH5, DNAH8, DNAH9, DNAH11, and DNAH17) (p = 8.5 × 10−47) were significantly enriched in hypospadias cases. The Dnah8 KO mice exhibited significantly decreased testosterone levels, which had an impact on urethral development and disrupted steroid biosynthesis. Combined with trios data, transcriptomic, and phenotypical and proteomic characterization of a mouse model, our work links ciliary genes with hypospadias. Overall, a panel of ODNAH genes with rare damaging variants was identified in 24% of hypospadias patients, providing significant insights into the underlying pathogenesis of hypospadias as well as genetic counseling.

Introduction Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China’s drug review and approval process.Methods and analysis This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period.Ethics and dissemination This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number NCT05271266.

Pectobacterium brasiliense (Pbr) has caused significant economic losses in major vegetable production areas in Northern China by causing bacterial soft rot in cash crops such as potatoes and cucumbers. This study aimed to establish a PMA-qPCR detection method for Pbr by screening specific and sensitive primers based on the glu gene and the conserved region of the 23S rRNA gene. Based on the optimized PMA pretreatment conditions, a standard curve was designed and constructed for PMA-qPCR detection (y = −3.391x + 36.28; R2 = 0.99). The amplification efficiency reached 97%, and the lowest detection limit of viable cells was approximately 2 × 102 CFU·mL−1. The feasibility of the PMA-qPCR method was confirmed through a manually simulated viable/dead cell assay under various concentrations. The analysis of potato tubers and cucumber seeds revealed that nine naturally collected seed samples contained a range from 102 to 104 CFU·g−1 viable Pbr bacteria. Furthermore, the system effectively identified changes in the number of pathogenic bacteria in cucumber and potato leaves affected by soft rot throughout the disease period. Overall, the detection and prevention of bacterial soft rot caused by Pbr is crucial.

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 individuals with intact periodontium were collected prior to any dental treatment, and levels of some key oral bacteria were quantitated using qPCR, and the medical and dental histories of participants were obtained retrospectively from axiUm. Data were analyzed statistically using SAS 9.4, IBM SPSS version 28, and R/RStudio version 4.1.2. Amongst racial/ethnic groups: 1) neighborhood medium incomes were significantly higher in the CA participants than the AA and the HA participants; 2) levels of bleeding on probing (BOP) were higher in the AAs than in the CAs and HAs; 3) Porphyromonas gingivalis levels were higher in the HAs compared to that in the CAs; 4) most P. gingivalis detected in the AAs were the fimA genotype II strain that was significantly associated with higher BOP indexes along with the fimA type IV strain. Our results suggest that socioeconomic disadvantages, higher level of P. gingivalis, and specific types of P. gingivalis fimbriae, particularly type II FimA, contribute to risks for development of periodontitis and periodontal health disparities.

The daylily (Hemerocallis citrina Baroni)/other crop intercropping system can be a specific and efficient cropping pattern in a horticultural field. Intercropping systems contribute to the optimization of land use, fostering sustainable and efficient agriculture. In the present study, high-throughput sequencing was employed to explore the diversity in the root-soil microbial community in the intercropping of four daylily intercropping systems [watermelon (Citrullus lanatus)/daylily (WD), cabbage (Brassica pekinensis)/daylily (CD), kale (Brassica oleracea)/daylily (KD), watermelon/cabbage/kale/daylily (MI)], and determine the physicochemical traits and enzymatic activities of the soil. The results revealed that the contents of available potassium (2.03%-35.71%), available phosphorus (3.85%-62.56%), available nitrogen (12.90%-39.52%), and organic matter (19.08%-34.53%), and the urease (9.89%-31.02%) and sucrase (23.63%-50.60%) activities, and daylily yield (7.43%- 30.46%) in different intercropping soil systems were significantly higher compared to those in the daylily monocropping systems (CK). The bacterial Shannon index increased significantly in the CD and KD compared to the CK. In addition, the fungi Shannon index was also increased significantly in the MI, while the Shannon indices of the other intercropping modes were not significantly altered. Different intercropping systems also caused dramatic architectural and compositional alterations in the soil microbial community. A prominently higher relative richness of Bacteroidetes was noted in MI compared to that in CK, while Acidobacteria in WD and CD and Chloroflexi in WD were pronouncedly less abundant compared to those in CK. Furthermore, the association between soil bacteria taxa and soil characteristic parameters was stronger than that between fungi and soil. In conclusion, the present study demonstrated that the intercropping of daylily with other crops could significantly improve the nutrient levels of the soil and optimize the soil bacterial microflora composition and diversity.

BackgroundBiliary atresia (BA) is a life-threatening disorder, which is characterized by the obliteration of biliary tracts. Heparan sulfate proteoglycans (HSPGs) are important regulators in liver diseases. Whether HSPGs participate in the development of BA is poorly understood.MethodsRNA-seq dataset GSE122340, including 171 BA and 7 normal liver tissue, was integrated for bioinformatic analysis. R function “wilcox.test” was used to compare HSPGs expression levels, and “cor.test” was used to evaluate the correlation analysis. MCPcounter was used to assess the abundance of immunocytes. Molecular subtypes of BA were clustered via NMF clustering and LASSO regression was applied to screen hub HSPGs genes in BA clusters. RT-PCR analysis was used to assess the expression of hub HSPGs in BA liver. Immunohistochemical staining and immunofluorescence assay were used to evaluated the location and expression of hub HSPGs in BA liver tissue.ResultsMajority of HSPGs was up-regulated in BA and correlated with liver fibrosis and ductular reaction markers. The abundance of immunocytes was higher in BA and associated with HSPGs. Based on the expression of HSPGs, BA patients were classified into 3 subtypes (C1, C2, and C3). Pathway enrichment analysis revealed C1 subtype had severe liver injury with SDC4 identified as the hub gene, while C3 subtype presented relatively normal liver condition with GPC3 identified as the hub gene. RT-PCR analysis demonstrated the expression levels of 2 hub genes in BA liver tissue with different jaundice clearance standards. Immunohistochemical staining and immunofluorescence assay showed that SDC4 was mostly expressed in ductular reaction area, while GPC3 was mostly expressed in hepatocytes.ConclusionMajority of HSPGs are aberrant expressed in BA. The subtype hub gene SDC4 and GPC3 might be used as a potential indicator for different types of prognosis.

Carbon‐supported nanoparticles (NPs) are widely used as catalysts in fuel cells and electrolyzers. While it is well known that NPs with smaller size and higher loading often lead to better catalytic activity, they remain challenging to synthesize due to the weak control over the surface properties of the support. Herein, a facile approach to synthesize carbon‐supported, high‐loading, and ultra‐small Pt3Ni NPs via applying thermal shock on strongly interacted carbon support with metal salt is reported. Specifically, sodium citrate is introduced into the precursor solution and substrate mixture, which induces strong electrostatic effect between metal salts and carbon particles that markedly improves precursor anchoring and dispersion, thereby achieving high particle loading as well as small size and distribution. As a proof‐of‐concept, the synthesis of Pt3Ni NPs supported on carbon black with particle size of 1.56 ± 0.36 nm at 30 wt% loading and 1.66 ± 0.56 nm at 40 wt% loading is reported, where the sizes are among the smallest while the loadings are among the highest in the literature. This approach can be readily extended to many compositions and substrates, with tunable particle size and loading, thereby substantially expanding the synthesis space for NP catalysts in various electrochemical applications.

Hyperactivation of Bruton’s tyrosine kinase (BTK) or interleukin-2-inducible T cell kinase (ITK) has been attributed to the pathogenesis of B-cell lymphoma or T-cell leukemia, respectively, which suggests that Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase are critical targets for the treatment of hematological malignancies. We identified a novel third-generation epidermal growth factor receptor (EGFR) inhibitor, ASK120067 (limertinib) in our previous research, which has been applied as a new drug application against non-small cell lung cancer in China. In this work, we found that ASK120067 displayed potent in vitro inhibitory efficacy against Bruton’s tyrosine kinase protein and interleukin-2-inducible T cell kinase protein via covalent binding. In cell-based assays, ASK120067 dose-dependently suppressed Bruton’s tyrosine kinase phosphorylation and exhibited anti-proliferation potency by inducing apoptosis in numerous B-lymphoma cells. Meanwhile, it caused growth arrest and induced the apoptosis of T-cell leukemia cells by attenuating interleukin-2-inducible T cell kinase activation. Oral administration of ASK120067 led to significant tumor regression in B-cell lymphoma and T-cell leukemia xenograft models by weakening Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase signaling, respectively. Taken together, our studies demonstrated that ASK120067 exerted preclinical anti-tumor activities against B-/T-cell malignancy by targeting BTK/ITK.

The diagnosis related group (DRG) was the most commonly used prospective hospital payment platform in developed countries. One of the major limitations of the DRG system is that the DRG grouping is not sufficiently homogeneous in benchmarking underlying resource needs. We developed a novel hospital payment and management system called Big Data Diagnosis & Intervention Packet (BD-DIP) by applying the similar case mix index (CMI) principles but the grouping is based on unique combination of ICD-10 and ICD-9 v3 codes. The initial prototype of BD-DIP was developed using hospital discharge records in Shanghai and then piloted in Guangzhou, China. The average coefficient of variation of the DB-DIP is about one-third smaller than the US DRG system. Results from the pilot evaluation showed that introduction of the BD-DIP lead to about 5% hospital budget savings and notable improvement in hospital care efficiency, including increased institutional CMI, lower admission rates, smaller variation in hospital charges, and lower patient cost-sharing burdens. The implementation of hospital monitoring tools resulted in identification of potential irregular practices to enable further auditing and investigation. The BD-DIP platform has a number of advantages over DRG-based payment models in terms of more homogeneous resource utilization within groups, design simplicity, dynamic in grouping, and reimbursement value in reflecting real-world treatment pathways and costs, and easy to implement.