Swimmers at interfaces enhance interfacial transport.

The behavior of fluid interfaces far from equilibrium plays central roles in nature and in industry. Active swimmers trapped at interfaces can alter transport at fluid boundaries with far reaching implications. Swimmers can become trapped at interfaces in diverse configurations and swim persistently in these surface adhered states. The self-propelled motion of bacteria makes them ideal model swimmers to understand such effects. We have recently characterized the swimming of interfacially trapped Pseudomonas aeruginosa PA01 moving in pusher mode. The swimmers adsorb at the interface with pinned contact lines, which fix the angle of the cell body at the interface and constrain their motion. Thus, swimmers become trapped at interfaces in diverse configurations and swim persistently in these surface adhered states. We observe that most interfacially trapped bacteria swim along circular paths. Fluid interfaces also typically form incompressible two-dimensional layers. These effects influence the flow generated by the swimmers. In our previous work, we have visualized the interfacial flow around a pusher bacterium and described the flow field using two dipolar hydrodynamic modes; one stresslet mode whose symmetries differ from those in bulk, and another bulk mode unique to incompressible fluid interfaces. Based on this understanding, swimmer-induced tracer displacements and swimmer-swimmer pair interactions are explored using analysis and experiment. The settings in which multiple interfacial swimmers with circular motion can significantly enhance interfacial transport of tracers or promote mixing of other swimmers on the interface are identified through simulations and compared to experiment. This study shows the importance of biomixing by swimmers at fluid interfaces and identifies important factors in the design of biomimetic active colloids to enhance interfacial transport.

Associations between serum ferritin baselines and trajectories and the incidence of metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

BACKGROUND AND AIMS: Evidence from prospective cohort studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and longitudinal changes in serum ferritin (SF) still limited. This study aimed to investigate the associations of SF baselines and trajectories with new-onset MASLD and to present a MASLD discriminant model. METHODS: A total of 1895 participants who attended health examinations at least three times in a hospital in Dalian City between 2015 and 2022 were included. The main outcome was the incidence of MASLD. The associations between SF baselines and trajectories with the risk of MASLD were analyzed by Cox proportional hazards regression, restricted cubic spline (RCS) analysis and time-dependent receiver operating characteristic (ROC) curve analysis. In addition, a MASLD discrimination model was established using logistic regression analyses. RESULTS: Among the 1895 participants, 492 developed MASLD during follow-up. Kaplan-Meier analysis indicated that participants in the low-stable trajectory group had a longer MASLD-free time compared with participants in other groups. Compared with those in the low-stable trajectory group, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of new-onset MASLD in the medium-high, high-stable and high-high trajectory groups were 1.54(1.18-2.00), 1.77(1.35-2.32) and 1.55(1.07-2.26), respectively (Ptrend < 0.001). The results were robust in subgroup and sensitivity analyses. Multivariate Cox proportional regression showed that SF was an independent risk factor of MASLD (HR = 1.002, 95%CI: 1.000-1.003, P = 0.003). The restricted cubic spline demonstrated a nonlinear relationship between SF and the risk of MASLD. The 8-variable model had high discriminative performance, good accuracy and clinical effectiveness. The ROC curve results showed that AUC was greater than that of the FLI, HSI and ZJU models (all P < 0.01). CONCLUSIONS: Not only a higher baseline SF but also SF changing trajectory are significantly associated with risk of new-onset MASLD. SF could be a predictor of the occurrence of MASLD.

Heterogeneity in the immune microenvironment of bone metastasis in driver-positive non-small cell lung cancer.

Mutations in epidermal growth factor receptor and anaplastic lymphoma kinase are common driver events in non-small cell lung cancer (NSCLC), which are associated with a high frequency of bone metastases (BMs). While the bone marrow represents a specialized immune microenvironment, the immune repertoire of BMs remains unknown. Considering the higher incidence of BMs in driver gene-positive NSCLCs, and the unique biology of the bone, herein, we assessed the infiltrating immune cells and T cell receptor (TCR) profile of BMs in driver-positive NSCLCs. Immune profile of BMs in driver gene-positive NSCLC were assessed in 10 patients, where 6 had driver gene-positive mutation. TCR and bulk RNA sequencing were performed on malignant bone samples. The diversity and clonality of the TCR repertoire were analyzed. The cellular components were inferred from bulk gene expression profiles computationally by CIBERSORT. Although BMs were generally regarded as immune-cold tumors, immune cell composition analyses showed co-existence of cytotoxic and suppressor immune cells in driver-positive BM samples, as compared to primary lung. Analysis of the TCR repertoire indicated a trend of higher diversity and similar clonality in the driver-positive compared with the driver-negative subsets. In addition, we identified two cases that showed the opposite response to immune checkpoint blockade. A comparison of these two patients' BM samples showed more highly amplified clones, fewer M2 macrophages and more activated natural killer cells in the responder. In summary, BMs in NSCLC are heterogeneous in their immune microenvironment, which might be related to differential clinical outcomes to immune checkpoint blockade.

Photocatalytic Co-Reduction of N2 and CO2 with CeO2 Catalyst for Urea Synthesis.

The effective conversion of carbon dioxide (CO2 ) and nitrogen (N2 ) into urea by photocatalytic reaction under mild conditions is considered to be a more environmentally friendly and promising alternative strategies. However, the weak adsorption and activation ability of inert gas on photocatalysts has become the main challenge that hinder the advancement of this technique. Herein, we have successfully established mesoporous CeO2-x nanorods with adjustable oxygen vacancy concentration by heat treatment in Ar/H2 (90 % : 10 %) atmosphere, enhancing the targeted adsorption and activation of N2 and CO2 by introducing oxygen vacancies. Particularly, CeO2 -500 (CeO2 nanorods heated treatment at 500 °C) revealed high photocatalytic activity toward the C-N coupling reaction for urea synthesis with a remarkable urea yield rate of 15.5 µg/h. Besides, both aberration corrected transmission electron microscopy (AC-TEM) and Fourier transform infrared (FT-IR) spectroscopy were used to research the atomic surface structure of CeO2 -500 at high resolution and to monitor the key intermediate precursors generated. The reaction mechanism of photocatalytic C-N coupling was studied in detail by combining Density Functional Theory (DFT) with specific experiments. We hope this work provides important inspiration and guiding significance towards highly efficient photocatalytic synthesis of urea.

Effects of SGLT2 inhibitors on haematocrit and haemoglobin levels and the associated cardiorenal benefits in T2DM patients: A meta-analysis.

To explore the effect and magnitude of effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on haematocrit and haemoglobin and the related cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM), PubMed, Web of Science, CENTRAL and EMBASE were searched to identify eligible trials. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Seventy-eight studies were included in the meta-analysis. SGLT2 inhibitors significantly increased haematocrit and haemoglobin levels compared with control (total WMD 2.27% [95% CI 2.08, 2.47] and 6.20 g/L [95% CI 5.68, 6.73], respectively). Except for dapagliflozin (p = 0.000), no notable dose-dependent relationship was revealed for other SGLT2 inhibitors. The effect could be sustained or even slightly increased with long-term therapy (coef. =0.009, 95% CI [0.005, 0.013], p = 0.000). In subgroup analyses, haematocrit elevation increased with higher body mass index (BMI). A greater haematocrit elevation could be observed in white patients or when compared with active controls. In conclusion, SGLT2 inhibitors increased haematocrit and haemoglobin levels in T2DM patients. Changes in haematocrit and haemoglobin seem to be surrogate markers of improvement in renal metabolic stress, and important mediators involved in cardiorenal protection.

Interfacial Flow around Brownian Colloids.

Understanding the flow created by particle motion at interfaces is a critical step toward understanding hydrodynamic interactions and colloidal self organization. We have developed correlated displacement velocimetry to measure flow fields around interfacially trapped Brownian particles. These flow fields can be decomposed into interfacial hydrodynamic multipoles, including force monopole and dipole flows. These structures provide key insights essential to understanding the interface's mechanical response. Importantly, the flow structure shows that the interface is incompressible for scant surfactant near the ideal gaseous state and contains information about interfacial properties and hydrodynamic coupling with the bulk fluid. The same dataset can be used to predict the response of the interface to applied, complex forces, enabling virtual experiments that produce higher order interfacial multipoles.

Motile Bacteria at Oil-Water Interfaces: Pseudomonas aeruginosa.

Bacteria are important examples of active or self-propelled colloids. Because of their directed motion, they accumulate near interfaces. There, they can become trapped and swim adjacent to the interface via hydrodynamic interactions, or they can adsorb directly and swim in an adhered state with complex trajectories that differ from those in bulk in both form and spatiotemporal implications. We have adopted the monotrichous bacterium Pseudomonas aeruginosa PA01 as a model species and have studied its motion at oil-aqueous interfaces. We have identified conditions in which bacteria swim persistently without restructuring the interface, allowing detailed and prolonged study of their motion. In addition to characterizing the ensemble behavior of the bacteria, we have observed a gallery of distinct trajectories of individual swimmers on and near fluid interfaces. We attribute these diverse swimming behaviors to differing trapped states for the bacteria in the fluid interface. These trajectory types include Brownian diffusive paths for passive adsorbed bacteria, curvilinear trajectories including curly paths with radii of curvature larger than the cell body length, and rapid pirouette motions with radii of curvature comparable to the cell body length. Finally, we see interfacial visitors that come and go from the interfacial plane. We characterize these individual swimmer motions. This work may impact nutrient cycles for bacteria on or near interfaces in nature. This work will also have implications in microrobotics, as active colloids in general and bacteria in particular are used to carry cargo in this burgeoning field. Finally, these results have implications in engineering of active surfaces that exploit interfacially trapped self-propelled colloids.

A Comparison of Response Time Threshold Scoring Procedures in Mitigating Bias From Rapid Guessing Behavior.

Rapid guessing (RG) is a form of non-effortful responding that is characterized by short response latencies. This construct-irrelevant behavior has been shown in previous research to bias inferences concerning measurement properties and scores. To mitigate these deleterious effects, a number of response time threshold scoring procedures have been proposed, which recode RG responses (e.g., treat them as incorrect or missing, or impute probable values) and then estimate parameters for the recoded dataset using a unidimensional or multidimensional IRT model. To date, there have been limited attempts to compare these methods under the possibility that RG may be misclassified in practice. To address this shortcoming, the present simulation study compared item and ability parameter recovery for four scoring procedures by manipulating sample size, the linear relationship between RG propensity and ability, the percentage of RG responses, and the type and rate of RG misclassifications. Results demonstrated two general trends. First, across all conditions, treating RG responses as incorrect produced the largest degree of combined systematic and random error (larger than ignoring RG). Second, the remaining scoring approaches generally provided equal accuracy in parameter recovery when RG was perfectly identified; however, the multidimensional IRT approach was susceptible to increased error as misclassification rates grew. Overall, the findings suggest that recoding RG as missing and employing a unidimensional IRT model is a promising approach.

Quality evaluation and health risk assessment of karst groundwater in Southwest China.

Groundwater in karst regions is of immense value due to its vital support for regional ecosystems and residents' livelihoods. However, it is simultaneously threatened by multi-source pollution from agricultural non-point sources, industrial and domestic point sources, and mining activities. This study focuses on the Guangxi of China, which features typical karst topography, aiming to thoroughly assess the groundwater quality and related health risks in Guangxi, especially identifying the impacts of various key pollution sources on the groundwater environment. A total of 1912 groundwater samples were collected, covering an area of approximately 237,600 km2. The spatial distribution of pollutants was analysed using the Nemeroww index method and Kriging interpolation, while multivariate statistical and cluster analysis methods were employed to identify the main types of pollution sources. Furthermore, based on the human health risk assessment model of the U.S. Environmental Protection Agency (US EPA), a risk assessment was conducted for key pollutants. The results revealed widespread heavy metal contamination in Guangxi's groundwater, particularly with concentrations of Mn, As, Al, Pb reaching up to 9.4 mg/L, 2.483 mg/L, 37.95 mg/L, 4.761 mg/L, respectively, significantly exceeding China's national Class III groundwater quality standards. Cluster analysis indicated that mining and industrial activities are the primary sources of pollution. The health risk assessment demonstrated that these activities pose a significant risk to public health. The aim of this study is to provide a scientific basis for the protection of the groundwater environment in Guangxi and other karst areas, the formulation of pollution prevention and control strategies, and the optimization of urban and industrial land use layouts. Future research should focus on advanced isotopic and molecular biological techniques to trace pollution sources more precisely and evaluate the effectiveness of pollution control measures.

Evaluation of groundwater quality with multi-source pollution based on source identification and health risks.

Groundwater is a crucial water supply source in Chengdu City, western China, a region experiencing significant water scarcity. The sources of inorganic pollutants in groundwater and their potential health risks are of great concern. In this study, based on 156 groundwater samples collected in 2021 in the study area were analyzed for hydrochemical characterization and controlling factors. The Positive Matrix Factorization (PMF) model was used for contaminant source analysis, and Monte Carlo Simulation (MCS) combined with the Health Risk Evaluation Model (HREM) was used to quantify the health risks. The results indicate that the groundwater in the study area is predominantly of the Ca·Na-SO4·HCO3, Ca·Na-HCO3·SO4 and Ca-HCO3·SO4 types, mainly influenced by the combination of evaporation-concentration-crystallization and rock leaching-weathering. K+, Na+, and Cl- mainly originate from the weathering and dissolution of potassium feldspar and rock salt, while Ca2+, Mg2+, HCO3-, and SO42- primarily come from the weathering and dissolution of sulfate minerals. The main sources of groundwater pollution and their contributions are as follows: domestic pollution (25.6 %), dissolution-filtration-evaporation-concentration action (22.8 %), hydrogeochemical evolution (15.8 %), water-rock interactions (12.8 %), primary geologic context (12.1 %), and agricultural non-point source pollution (11.0 %). Cl- and As are the primary contributors to non-carcinogenic and carcinogenic risks, respectively. Non-carcinogenic risks are below USEPA standards, while the average carcinogenic risk for arsenic exceeded the maximum acceptable risk level thresholds by 23 and 109 times for adults and children, respectively. Non-carcinogenic and carcinogenic health risks were mainly influenced by pollutant concentrations. The primary geological background and domestic pollution contributed the most to the non-carcinogenic risk for adults (50.3 %) and children (77.1 %), and 38.2 % and 10.3 %, respectively. This study highlights the necessity of establishing a comprehensive groundwater pollution monitoring system, enhancing industrial waste management practices, and raising public awareness to mitigate contamination and ensure the sustainable use of groundwater resources in Chengdu City.

ARDS in solid organ transplant recipients hospitalized for COVID-19 based on the 2023 new definition.

BACKGROUND: Solid organ transplant recipients (SOTRs) are more likely to suffer complications after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVES: We aimed to describe the clinical features of SOTRs infected with SARS-CoV-2 and to assess independent risk factors associated with the development of acute respiratory distress syndrome (ARDS) following COVID-19 infection in SOTRs based on the new ARDS definition. METHODS: 358 SOTRs infected with SARS-CoV-2 were recruited and divided into two groups, patients with ARDS (n = 81) and patients without ARDS (n = 277). Demographic data, initial laboratory findings, therapeutic measures, and outcome indicators were compared between the two groups. The association between the onset of ARDS and related factors was analyzed using a logistic regression model. A nomogram was created to estimate the probability of developing ARDS. RESULTS: Approximately 22.6 % (81/358) of hospitalized SOTRs infected with SARS-CoV-2 developed ARDS. In comparison to patients without ARDS, those with ARDS presented with more underlying conditions, decreased lymphocyte counts and serum albumin levels, but increased levels of leukocytes, serum creatinine, nitrogen urea, uric acid, and inflammatory markers. Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS in this population. Furthermore, a nomogram prediction model was created utilizing the aforementioned factors to facilitate early prediction of ARDS, exhibiting an AUC (area under curve) of 0.81. CONCLUSIONS: Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS following COVID-19 infection in SOTRs.

Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy.

Background: Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analysed the clinicopathological features and risk factors for AKI and relapse in lupus podocytopathy patients. Methods: The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022 and was divided into the mild glomerular lesion (MGL) and focal segmental glomerulosclerosis (FSGS) groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regressions were employed to identify the risk factors for AKI and relapse, respectively. Results: Among 6052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in the CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared with the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and haematuria; in addition, they had higher Systemic Lupus Erythematosus Disease Activity Index 2000, ATI and CTI scores but a significantly lower CRR rate. Urinary protein ≥7.0 g/24 h and serum C3 ≤0.750 g/l were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for kidney relapse. Conclusions: In this study, histological subtypes of lupus podocytopathy were found to be associated with clinical features and treatment response. In addition, several risk factors associated with AKI occurrence and kidney relapse were identified.

Effect of Missed Post-Procedure Creatinine Measurement on Sub-Acute Kidney Injury Following Coronary Angiography.

Serum creatinine (SCr) levels are essential for the diagnosis of kidney disease after coronary angiography (CAG). However, the influence of missed post-procedure SCr measurement in this situation is unclear. The present study included 14,127 patients undergoing CAG as part of the Cardiorenal ImprovemeNt registry II. Patients were divided into two groups according to whether a post-procedure SCr was measured within 3 days. The primary endpoint was acute kidney disease (AKD). Logistic regression was used to evaluate the relationship between post-procedure SCr and AKD. Of the 14,127 patients (61.6 ± 9.8 years, 34.2% females), 55.4% (n = 7822) did not have a post-procedure SCr measurement. The incidence of AKD was higher in the missed post-procedure SCr group (15.7 vs 11.9%; median follow-up 6.54 years). Multivariate logistic regression showed that missed post-procedure SCr measurement was associated with significantly higher risk of AKD (adjusted odds ratio [aOR]: 1.26, 95% CI: 1.10-1.45, P < .001). The results were more significant in patients with normal renal function at baseline (aOR: 1.36, 95% CI: 1.16-1.60, P < .001). In our study, over half of the patients undergoing CAG missed their post-procedure SCr measurement. The missed post-procedure SCr group had a significantly higher risk of developing AKD compared with those with a post-procedure SCr measurement.

Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

ZBP1 and heatstroke.

Heatstroke, which is associated with circulatory failure and multiple organ dysfunction, is a heat stress-induced life-threatening condition characterized by a raised core body temperature and central nervous system dysfunction. As global warming continues to worsen, heatstroke is expected to become the leading cause of death globally. Despite the severity of this condition, the detailed mechanisms that underlie the pathogenesis of heatstroke still remain largely unknown. Z-DNA-binding protein 1 (ZBP1), also referred to as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, was initially identified as a tumor-associated and interferon (IFN)-inducible protein, but has recently been reported to be a Z-nucleic acid sensor that regulates cell death and inflammation; however, its biological function is not yet fully understood. In the present study, a brief review of the main regulators is presented, in which the Z-nucleic acid sensor ZBP1 was identified to be a significant factor in regulating the pathological characteristics of heatstroke through ZBP1-dependent signaling. Thus, the lethal mechanism of heatstroke is revealed, in addition to a second function of ZBP1 other than as a nucleic acid sensor.

Estimation of life history traits and stock status for Scomber japonicus based on data-limited method.

The age-structure data is usually unavailable for most traditional fishery species in the East China Sea. The data-limited method is thus particularly important to understand life history and population dynamics of commercial fishes. At the offshore waters of southern Zhejiang, Chub mackerel (Scomber japonicus) is one of the dominant economic species. Based on fork length data from 2016 to 2020, we estimated its life history traits with the data-limited method, including the growth parameters and mortality coefficients. We further evaluated the status of Chub mackerel by the yield per recruitment (YPR) model. The results showed that the relationship between fork length (L) and body weight (W) based on 1606 samples was estimated to be W=4.18×10-3L3.28(R2=0.96). The asymptotic fork length L∞ of Chub mackerel was 28.34 cm, the growth rate was 0.36 a-1, and the initial theoretical age was -0.40 a. The total mortality was estimated as 1.67 a-1, and the estimated natural mortality (M) was 0.85 a-1. The fishing mortality (F) was 0.82 a-1, and the development rate was 0.49. The current capture age was estimated to be 1.78 a, while the capture fork length was 15.44 cm. The YPR model results showed YPR value showed a trend of increasing and then decreasing with the increases of F. The values of biological reference points F0.1 and Fmax were 0.97 a-1 and 4.55 a-1, respectively, which were higher than the value of current F. The sensitivity analysis showed that the uncertainty of M greatly influenced the estimation results of YPR and biological reference points. A decrease in M significantly increased the YPR value, but F0.1 and Fmax decreased. The status of Chub mackerel stock at the offshore waters of southern Zhejiang is in good condition. However, the miniaturization of catch is intensifying. It is recommended to extend the capture fork length to 20 cm (the impact point age) to improve the quality of the catch, which would sustainably use the Chub mackerel resources.

Circ_0001602 aggravates the progression of acute myeloid leukemia by regulating the miR-192-5p/ZBTB20 axis.

BACKGROUND: Acute myeloid leukemia (AML) is a malignant blood cancer with a poor prognosis and complex pathogenesis. Recently, the critical role of circular RNAs (circRNAs) has been demonstrated in the malignant progression of AML. This study aimed to investigate the functional role and underlying mechanism of circ_0001602 in AML development. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted for detecting the expression of circ_0001602, CCND3, microRNA-192-5p (miR-192-5p), and Zinc Finger and BTB Domain-Containing Protein 20 (ZBTB20) mRNA. RNase R assay and Actinomycin D assay were implemented to determine the characteristics of circ_0001602. Cell counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Flow cytometry was employed for assessing cell cycle distribution and apoptosis. Dual-luciferase reporter assay and RIP assay were utilized for confirming the interactions between miR-192-5p and circ_0001602 or ZBTB20. RESULTS: Circ_0001602 and ZBTB20 were upregulated and miR-192-5p level was reduced in AML tissues and cells. Depletion of circ_0001602 repressed cell proliferation and induced cell cycle arrest and apoptosis in AML cells. Functionally, circ_0001602 was identified to be the sponge of miR-192-5p, and miR-192-5p silence restored the suppressive effects of circ_0001602 knockdown on AML cell progression. Furthermore, ZBTB20 was a target of miR-192-5p, and ZBTB20 overexpression neutralized the miR-192-5p-mediated inhibiting actions on the malignant phenotypes of AML cells. Besides, circ_0001602 could sponge miR-192-5p to positively regulate ZBTB20 expression. CONCLUSION: Circ_0001602 contributed to AML cell development at least partially through modulating the miR-192-5p/ZBTB20 axis, which provided new insights for AML treatment.

The differences in virus shedding time between the Delta variant and original SARS-CoV-2 infected patients.

Background: The worldwide epidemic of Coronavirus Disease 2019 (COVID-19) has evolved into multiple variants. The Delta variant is known for its ability to spread and replicate, while data are limited about the virus shedding time in patients infected by the Delta variant. Methods: 56 Delta variant and 56 original SARS-CoV-2 infected patients from Hunan, China, matched according to age and gender divided into two groups and compared the baseline characteristics and laboratory findings with appropriate statistical methods. Results: Patients infected with the Delta variant had significantly fewer symptoms of fever (p < 0.001), fatigue (p = 0.004), anorexia (p < 0.001), shortness of breath (p = 0.004), diarrhea (p = 0.006), positive pneumonia rate of chest CT (p = 0.019) and chest CT ground glass opacities (p = 0.004) than those of patients with the original SARS-CoV-2. Patients of the Delta variant group had a significantly longer virus shedding time [41.5 (31.5, 46.75) vs. 18.5 (13, 25.75), p < 0.001] compared with the original SARS-CoV-2 group. The correlation analyses between the virus shedding time and clinical or laboratory parameters showed that the virus shedding time was positively related to the viral strain, serum creatinine and creatine kinase isoenzyme, while negatively correlated with lymphocyte count, total bilirubin and low-density lipoprotein. Finally, the viral strain and lymphocyte count were thought of as the independent risk factors of the virus shedding time demonstrated by multiple linear regression. Conclusion: COVID-19 patients infected with the Delta variant exhibited fewer gastrointestinal symptoms and prolonged virus shedding time than those infected with the original SARS-CoV-2. Delta variant and fewer lymphocyte were correlated with prolonged virus shedding time.