Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.

BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. RESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. CONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.

Association of medical care capacity and the patient mortality of septic shock: a cross-sectional study.

BACKGROUND: Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time. METHODS: Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively. MAIN RESULTS: The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], -0.2532 [-0.5038, -0.0026]) (p-value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], -0.370 [-0.591, -0.150], -0.136 [-0.241, -0.031], and -0.774 [-1.158, -0.389]) (p-value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p-value < 0.001). CONCLUSIONS: Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality.

Highly efficient and selective removal of anionic dyes from aqueous solutions using polyacrylamide/peach gum polysaccharide/attapulgite composite hydrogels with positively charged hybrid network.

To avoid the weakness (lower adsorption rate and selectivity) of peach gum polysaccharide (PGP) and improve the adsorption performance of polyacrylamide (PAAm) hydrogel (lower adsorption capacity), in the present work, the PGP was chemically tailored to afford ammoniated PGP (APGP) and quaternized PGP (QPGP), and attapulgite (ATP) was bi-functionalized with cation groups and carbon­carbon double bond. Then, PAAm/APGP and PAAm/QPGP/ATP hydrogels were synthesized via redox polymerization. The synthesis procedure and properties of hydrogels were traced by FTIR, SEM, XPS, TGA, TEM, and BET methods, and the dye adsorption performance of the hydrogels was evaluated using the new coccine (NC) and tartrazine (TTZ) aqueous solutions as the model anionic dyes. Effects of initial dye concentration, pH, and ionic strength on the adsorption were investigated. Compared with PAAm/APGP hydrogel, PAAm/APGP/ATP hydrogel exhibits higher adsorption rate, superior adsorption capacity, stability, and selectivity towards anionic dye. The adsorption process of PAAm/QPGP/ATP hydrogel reached equilibrium in about 20 min and followed the pseudo-second-order kinetic model and Langmuir isotherm. The adsorption capacities towards NC and TTZ of PAAm/QPGP/ATP hydrogel were calculated as 873.235 and 731.432 mg/g. This hydrogel adsorbent originating from PAAm, PGP, and ATP shows great promise for application in practical water treatment.

Thermally-resilient, phase-invertible, ultra-stable all-aqueous compartments by pH-modulated protein colloidal particles.

The essence of compartmentalization in cells is the inspiration behind the engineering of synthetic counterparts, which has emerged as a significant engineering theme. Here, we report the formation of ultra-stable water-in-water (W/W) emulsion droplets. These W/W droplets demonstrate previously unattained stability across a broad pH spectrum and exhibit resilience at temperatures up to 80℃, overcoming the challenge of insufficient robustness in dispersed droplets of aqueous two-phase systems (ATPS). The exceptional robustness is attributed to the strong anchoring of micelle-like casein colloidal particles at the PEO/DEX interface, which maintains stability under varying environmental conditions. The increased surface hydrophobicity of these particles at high temperatures contributes to the formation of thermally-stable droplets, enduring temperatures as high as 80℃. Furthermore, our study illustrates the adaptable affinity of micelle-like casein colloidal particles towards the PEO/DEX-rich phase, enabling the formation of stable DEX-in-PEO emulsions at lower pH levels, and PEO-in-DEX emulsions as the pH rises above the isoelectric point. The robust nature of these W/W emulsions unlocks new possibilities for exploring various biochemical reactions within synthetic subcellular modules and lays a solid foundation for the development of novel biomimetic materials.

Multicompartmental coacervate-based protocell by spontaneous droplet evaporation.

Hierarchical compartmentalization, a hallmark of both primitive and modern cells, enables the concentration and isolation of biomolecules, and facilitates spatial organization of biochemical reactions. Coacervate-based compartments can sequester and recruit a large variety of molecules, making it an attractive protocell model. In this work, we report the spontaneous formation of core-shell cell-sized coacervate-based compartments driven by spontaneous evaporation of a sessile droplet on a thin-oil-coated substrate. Our analysis reveals that such far-from-equilibrium architectures arise from multiple, coupled segregative and associative liquid-liquid phase separation, and are stabilized by stagnation points within the evaporating droplet. The formation of stagnation points results from convective capillary flows induced by the maximum evaporation rate at the liquid-liquid-air contact line. This work provides valuable insights into the spontaneous formation and maintenance of hierarchical compartments under non-equilibrium conditions, offering a glimpse into the real-life scenario.

Solanine induces ferroptosis in colorectal cancer cells through ALOX12B/ADCY4 molecular axis.

OBJECTIVES: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Solanine is a phytochemical extracted from traditional Chinese medicine with widely reported anticancer effects. Here, we investigated the potential role of solanine in regulating ferroptosis in CRC cells and scrutinized the molecular mechanism. METHODS: Cell growth and cytotoxicity were examined using CCK-8 proliferation assay and lactate dehydrogenase assay. Oxidative stress was determined by measuring glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels. Subcellular changes in mitochondria were examined by transmission electron microscopy. Gene and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction was determined by co-immunoprecipitation. KEY FINDINGS: Solanine arrested cell proliferation in CRC cells and induced typical ferroptotic changes. Solanine treatment promoted ROS production, lipid peroxidation, and cell membrane disruption, while the cellular level of antioxidant GSH was reduced upon solanine treatment. ALOX12B was identified as a molecular mediator of solanine to promote ferroptosis. Solanine treatment upregulated ALOX12B levels and silencing ALOX12B could suppress solanine-induced ferroptosis. Further, ADCY4 was found to physically associate with ALOX12B and maintain ALOX12B protein stability. Silencing ADCY4 destabilized ALOX12B and attenuated solanine-induced ferroptosis. CONCLUSIONS: Our data demonstrated the ferroptosis-inducing effect of solanine in CRC cells, and revealed ALOX12B/ADCY4 molecular axis as the ferroptosis mediator of solanine. Solanine may synergize with existing ferroptosis inducer as an anticancer strategy in CRC, which warrants further validation in animal experiments.

Factors influencing DVT formation in sepsis.

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

Quality indicators for epilepsy management in China: The development of a tool to assess care and first three-year report.

OBJECTIVES: Epilepsy care in China has expanded considerably in the last decade but still remains largely unknown; we developed an easy-to-use tool to assess its quality. METHODS: We adapted the Epilepsy Update Quality Measurement, produced by the American Academy of Neurology (AAN) for use in China: The Quality Indicator for Epilepsy Treatment-China National Action (QUIET-CHINA). This tool incorporates a standardized case report form initially for logging quality indicators for people with epilepsy during in-patient stays. Nine quality indicators covered seizures, drugs, diagnostics, screening for co-morbid conditions, counseling for woman of child bearing age, and a composite indicator was further proposed by total number of interventions performed divided by the total number of people eligible in each indicator. The tool also has an electronic reporting and data feedback system. 96 epilepsy centers in 31 jurisdictions in mainland China have been piloted since 2017. RESULTS: Data from 11,600 individuals with epilepsy in the first 3-year study period were analyzed. The median age was 31; 60% were male. The composite indicators were 74%. Seizure freedom rate was less than 25% in all epilepsy types and post-surgical seizure freedom rate was 21%. 90% had seizure type and frequency, antiepileptic drugs recorded, while only 70% with active epilepsy were on regular antiepileptic drugs treatment. Investigations for diagnosis and etiology were performed in around 90% but screening for co-morbid conditions and counseling for women of childbearing potential was 38% and 15% respectively. Severe side effect happened in 2% individuals during the treatment. CONCLUSION: The preliminary results of the national action provided some baseline information. Except for an overall improvement, a significant treatment gap still exists, and psychiatric co-morbidities or issues affecting women are not seen as a priority. QUIET-CHINA will be expanded to more and other levels of hospitals, to help narrow the treatment gap and equalize the comprehensive epilepsy care on the national level.

Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022.

BACKGROUND: Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China. METHODS: Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran's I  analysis. RESULTS: The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran's I <0) and percentage of urban population (Moran's I <0), and positively correlated with the number of pediatric beds per million population (Moran's I >0). CONCLUSION: The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.

Identification of factors driving the spatial distribution of molybdenum (Mo) in topsoil in the Longitudinal Range-Gorge Region of Southwestern China using the Geodetector model.

As a key component of plant nitrogen-fixing enzymes and a variety of human coenzyme factors, molybdenum (Mo) plays an essential role in supporting both plant growth and human health. Soil is a key medium for the cycling of Mo in the biosphere. However, the driving anthropogenic and natural factors governing the spatial distribution of Mo in soil and their interactions are not well understood. To determine the factors that affect the spatial patterns of Mo in topsoil, 6980 samples were collected from the Longitudinal Range-Gorge Region (Linshui County, Sichuan Province, China). In this area, tall mountains are adjacent to deep valleys. Topsoil with enriched Mo is mostly distributed in mountainous areas. The most important factors influencing Mo in topsoil are soil parent materials (q = 0.482), altitude (q = 0.256), and soil type (q = 0.259). There are synergistic effects among the various driving factors [q(X1 âˆ© X2) > Max[q(X1), q(X2)]]. The Geodetector model was used to validate the magnitude of the interaction effects. The contribution to interacting factors is nonlinearly enhanced when the contribution of a single factor was low (any two factors of aspect, road distance, land use type, and S). The contribution to interacting factors is enhanced bidirectionally when the contribution of a single factor was high (any two factors of altitude, soil type, soil parent material, OM, and TFe2O3). When the contribution of one factor is high and the other is low, the contributing to interacting factors is mostly enhanced bidirectionally and a few are nonlinearly enhanced.

Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients-the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019.

This cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-related complications and prognosis. The reintubation rate within 48 hours after extubation and the total ICU mortality rate were independent risk factors for higher in-hospital mortality of V-V ECMO-supported patients (cutoff: 1.5% and 7.0%; 95% confidence interval: 1.05-1.48 and 1.04-1.45; odds ratios: 1.25 and 1.23; P = 0.012 and P = 0.015, respectively). Meanwhile, the V-V ECMO center volume was a protective factor (cutoff of ≥ 50 cases within the 3-year study period; 95% confidence interval: 0.57-0.83, odds ratio: 0.69, P = 0.0001). The subgroup analysis of 864 patients in 11 high-volume centers further strengthened these findings. Thus, ICU quality may play an important role in improving the prognosis of V-V ECMO-supported patients.

Primulaxilingensis (Primulaceae), a new species from Sichuan, China.

A new species, Primulaxilingensis K.Huang & Z.X.Fu, sp. nov. (Primulaceae), is described and illustrated. In gross morphology, it is clearly allied to section Minutissimae on account of having stolons, being glabrous, leaf rosette less than or equal to corolla, flower solitary and bract not swollen at base. The new species is easily distinguished by the combination of scape densely yellow farinose, leaf apex acute, rarely broadly obtuse, corolla pale purplish blue and style 3.0-6.0 mm above base of corolla tube, stamens reaching the corolla tube mouth in thrum flower. In addition, the distribution map, morphological comparison of related species and conservation status of the new species are also provided.

Multidimensional dynamic prediction model for hospitalized patients with the omicron variant in China.

Purpose: To establish dynamic prediction models by machine learning using daily multidimensional data for coronavirus disease 2019 (COVID-19) patients. Methods: Hospitalized COVID-19 patients at Peking Union Medical College Hospital from Nov 2nd, 2022, to Jan 13th, 2023, were enrolled in this study. The outcome was defined as deterioration or recovery of the patient's condition. Demographics, comorbidities, laboratory test results, vital signs, and treatments were used to train the model. To predict the following days, a separate XGBoost model was trained and validated. The Shapley additive explanations method was used to analyze feature importance. Results: A total of 995 patients were enrolled, generating 7228 and 3170 observations for each prediction model. In the deterioration prediction model, the minimum area under the receiver operating characteristic curve (AUROC) for the following 7 days was 0.786 (95% CI 0.721-0.851), while the AUROC on the next day was 0.872 (0.831-0.913). In the recovery prediction model, the minimum AUROC for the following 3 days was 0.675 (0.583-0.767), while the AUROC on the next day was 0.823 (0.770-0.876). The top 5 features for deterioration prediction on the 7th day were disease course, length of hospital stay, hypertension, and diastolic blood pressure. Those for recovery prediction on the 3rd day were age, D-dimer levels, disease course, creatinine levels and corticosteroid therapy. Conclusion: The models could accurately predict the dynamics of Omicron patients' conditions using daily multidimensional variables, revealing important features including comorbidities (e.g., hyperlipidemia), age, disease course, vital signs, D-dimer levels, corticosteroid therapy and oxygen therapy.

Effectiveness of an artificial intelligence clinical assistant decision support system to improve the incidence of hospital-associated venous thromboembolism: a prospective, randomised controlled study.

BACKGROUND: Thromboprophylaxis has been determined to be safe, effective and cost-effective for hospitalised patients at venous thromboembolism (VTE) risk. However, Chinese medical institutions have not yet fully used or improperly used thromboprophylaxis. The effectiveness of information technology applied to thromboprophylaxis in hospitalised patients has been proved in many retrospective studies, lacking of prospective research evidence. METHODS: All hospitalised patients aged >18 years not discharged within 24 hours from 1 September 2020 to 31 May 2021 were prospectively enrolled. Patients were randomly assigned to the control (9890 patients) or intervention group (9895 patients). The control group implemented conventional VTE prevention programmes; the intervention group implemented an Artificial Intelligence Clinical Assistant Decision Support System (AI-CDSS) on the basis of conventional prevention. Intergroup demographics, disease status, hospital length of stay (LOS), VTE risk assessment and VTE prophylaxis were compared using the χ2 test, Fisher's exact test, t-test or Wilcoxon rank-sum test. Univariate and multivariate logistic regressions were used to explore the risk factor of VTE. RESULTS: The control and intervention groups had similar baseline characteristics. The mean age was 58.32±15.41 years, and mean LOS was 7.82±7.07 days. In total, 5027 (25.40%) and 2707 (13.67%) patients were assessed as having intermediate-to-high VTE risk and high bleeding risk, respectively. The incidence of hospital-associated VTE (HA-VTE) was 0.38%, of which 86.84% had deep vein thrombosis. Compared with the control group, the incidence of HA-VTE decreased by 46.00%, mechanical prophylaxis rate increased by 24.00% and intensity of drug use increased by 9.72% in the intervention group. However, AI-CDSS use did not increase the number of clinical diagnostic tests, prophylaxis rate or appropriate prophylaxis rate. CONCLUSIONS: Thromboprophylaxis is inadequate in hospitalised patients with VTE risk. The role of AI-CDSS in VTE risk management is unknown and needs further in-depth study. TRIAL REGISTRATION NUMBER: ChiCTR2000035452.

Carbapenem is not always the best choice in the treatment of septic shock.

BACKGROUND: Septic shock is a global public health burden. In addition to the improvement of the level of individual care, the improvement of the overall hospital quality control management is also an essential key aspect of the Surviving Sepsis Campaign (SSC). Using of antibiotics is a cornerstone in the treatment of septic shock, so we conducted this study to investigate the influence of antibiotics and pathogenic bacteria on the mortality of septic shock at the level of overall hospital in China. METHODS: This was an observational database study in 2021 enrolled the data of 787 hospitals from 31 provinces/municipalities/autonomous regions of Mainland China collected in a survey from January 1, 2021 to December 31, 2021. RESULTS: The proportion of ICU patients with septic shock was 3.55%, while the patient mortality of septic shock was 23.08%. While carbapenem was the most preferred antibiotic medication used in 459 of the 782 hospitals, the preference for carbapenem did not show significant effect on the patient mortality in the treatment of septic shock (p-value 0.59). Compared with patients with fermenting bacteria as the most common pathogenic bacteria causing septic shock, patients with non-fermenting bacteria had a higher mortality (p-value 0.01). CONCLUSIONS: Whether using carbapenem as the preferred antibiotic or not, did not show effect on the patient mortality of septic shock. Compared with patients with fermenting bacteria as the most common pathogenic bacteria, patients of septic shock with non-fermenting bacteria had a higher mortality.

Cadmium accumulation in paddy soils affected by geological weathering and mining: Spatial distribution patterns, bioaccumulation prediction, and safe land usage.

The abnormal enrichment of cadmium (Cd) in soil caused by rock weathering and mining activities is an issue in southern China. Although the soil Cd content in these regions is extremely high, the bioavailability of Cd in the soils differs significantly. The carbonate area (CBA) and tin-mining area (TIA) in Hezhou City were investigated to determine the primary features of soil Cd mobility in these regions and improve environmental management. Lateral and vertical spatial distributions revealed different accumulation and migration mechanisms of soil Cd in the CBA and TIA. Further analyses revealed that mining activities and geological weathering resulted in different soil geochemical parameters, thus yielding significantly lower levels of Cd in rice grains in the CBA than in the TIA. The random forest (RF) model predicted the bioaccumulation factor (BAF) (R2 = 0.69) better than the support vector machine (SVM) model (R2 = 0.68). Subsequently, a novel land management scheme was proposed based on soil Cd and the prediction of Cd in rice to optimize the spatial resources of agricultural land and ensure the safety of rice for consumption. This study provides a novel approach for land management in Cd-contaminated areas.

A novel Natural killer cell-related gene signature for improving the prediction of prognosis and immunotherapy response in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA. METHODS: We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment. RESULTS: We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells. CONCLUSION: to sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.

Measuring the worldwide spread of COVID-19 using a comprehensive modeling method.

BACKGROUND: With the global spread of COVID-19, detecting high-risk countries/regions timely and dynamically is essential; therefore, we sought to develop automatic, quantitative and scalable analysis methods to observe and estimate COVID-19 spread worldwide and further generate reliable and timely decision-making support for public health management using a comprehensive modeling method based on multiple mathematical models. METHODS: We collected global COVID-19 epidemic data reported from January 23 to September 30, 2020, to observe and estimate its possible spread trends. Countries were divided into three outbreak levels: high, middle, and low. Trends analysis was performed by calculating the growth rate, and then country grouping was implemented using group-based trajectory modeling on the three levels. Individual countries from each group were also chosen to further disclose the outbreak situations using two predicting models: the logistic growth model and the SEIR model. RESULTS: All 187 observed countries' trajectory subgroups were identified using two grouping strategies: with and without population consideration. By measuring epidemic trends and predicting the epidemic size and peak of individual countries, our study found that the logistic growth model generally estimated a smaller epidemic size than the SEIR model. According to SEIR modeling, confirmed cases in each country would take an average of 9-12 months to reach the outbreak peak from the day the first case occurred. Additionally, the average number of cases at the peak time will reach approximately 10-20% of the countries' populations, and the countries with high trends and a high predicted size must pay special attention and implement public health interventions in a timely manner. CONCLUSIONS: We demonstrated comprehensive observations and predictions of the COVID-19 outbreak in 187 countries using a comprehensive modeling method. The methods proposed in this study can measure COVID-19 development from multiple perspectives and are generalizable to other epidemic diseases. Furthermore, the methods also provide reliable and timely decision-making support for public health management.

Spatially varying relationships of soil Se concentration and rice Se concentration in Guangxi, China: A geographically weighted regression approach.

In recent years, the biogeochemical behavior and environmental impact of Selenium (Se) on soil-plant systems have received widespread attention, and traditional statistical methods reveal generally positive correlations between rice Se and soil Se. However, that initial positive relationship may have been obscured by local external factors. Using local scale data from the geochemical evaluation of land quality project, this work employed geographically weighted regression (GWR) to examine the spatial variation of rice Se (as the dependent variable) and soil Se (as the independent variable) in Guangxi. Strong and weak correlation coefficients occur between rice Se and soil Se, thereby indicating that their relationships are spatially varying. Guangxi is characterized by significantly positive correlations in most areas, with weak correlations mostly found in the south-western and central-eastern regions. Areas with weak correlation can be divided into two patterns: high soil Se with low rice Se and high rice Se with low soil Se. The unique patterns are correlated with distinct natural factors, particularly the abundance of Fe-rich soils in the carbonate area; by contrast, sandstone areas in central Guangxi may have been affected by anthropogenic activities. To reveal the spatially varying relationships at the local scale, we employed GWR, an effective tool that allowed us to identify the association between environmental variables and influencing factors and explore spatially varying relationships between them. This study breaks through the existing understanding that soil Se is completely positively correlated with rice Se for the first time, and concludes that their correlation is spatially variable, providing an effective approach for the study of complex relationships.

Facile and Programmable Capillary-Induced Assembly of Prototissues via Hanging Drop Arrays.

An important goal for bottom-up synthetic biology is to construct tissue-like structures from artificial cells. The key is the ability to control the assembly of the individual artificial cells. Unlike most methods resorting to external fields or sophisticated devices, inspired by the hanging drop method used for culturing spheroids of biological cells, we employ a capillary-driven approach to assemble giant unilamellar vesicles (GUVs)-based protocells into colonized prototissue arrays by means of a coverslip with patterned wettability. By spatially confining and controllably merging a mixed population of lipid-coated double-emulsion droplets that hang on a water/oil interface, an array of synthetic tissue-like constructs can be obtained. Each prototissue module in the array comprises multiple tightly packed droplet compartments where interfacial lipid bilayers are self-assembled at the interfaces both between two neighboring droplets and between the droplet and the external aqueous environment. The number, shape, and composition of the interconnected droplet compartments can be precisely controlled. Each prototissue module functions as a processer, in which fast signal transports of molecules via cell-cell and cell-environment communications have been demonstrated by molecular diffusions and cascade enzyme reactions, exhibiting the ability to be used as biochemical sensing and microreactor arrays. Our work provides a simple yet scalable and programmable method to form arrays of prototissues for synthetic biology, tissue engineering, and high-throughput assays.