Machine learning is an effective method to predict the 3-month prognosis of patients with acute ischemic stroke.

Background and objectives: Upwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients. Methods: A total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient' demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants' prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables. Results: Feature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900. Conclusion: These findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.

[Simultaneous detection of lower aliphatic amines and conventional cations in atmospheric PM2.5 particulates by ion chromatography].

Many amine pollutants exist in the atmosphere. Lower aliphatic amines promote the formation and growth of particles into PM2.5, which damages the heart, lungs, and kidneys of the human body. PM2.5, a common atmospheric particulate pollutant with complex compositions, is the main cause of haze weather. Therefore, measuring the contents of lower aliphatic amines and cations in PM2.5 is of great significance for monitoring environmental air quality and protecting human health. This study established a suppressed ion-chromatographic method with conductivity for the simultaneous detection of four lower aliphatic amines (methylamine, dimethylamine, trimethylamine, and ethylamine) and five cations (Na+, N[Formula: see text], and Ca2+ showed high concentrations. The contents of the four lower aliphatic amines were low; however, the ethylamine content in some samples was high. The results indicate that the proposed method meets the quantification requirements for cations and lower aliphatic amines in PM2.5, with simple processing, high sensitivity, and good accuracy. It can quickly and accurately detect a large number of samples and be used to assess the pollution of small particles in the air as well as trace pollution sources to protect human health.

Deciphering the reduction of antibiotic resistance genes (ARGs) during medium-chain fatty acids production from waste activated sludge: Driven by inhibition of ARGs transmission and shift of microbial community.

Medium-chain fatty acids (MCFAs) production from waste activated sludge (WAS) by chain extension (CE) is a promising technology. However, the effects and mechanisms of CE process on the fate of antibiotic resistance genes (ARGs) remain unclear. In this study, the results showed that the removal efficiency of ARGs was 81.15 % in CE process, suggesting its efficacy in reducing environmental risks. Further, the observed decrease in mobile genetic elements (MGEs) indicated that CE process restricted the horizontal gene transfer (HGT). Complementing this, the increase in soluble organic matters and extracellular 16 S rDNA confirmed that MCFAs production caused bacterial damage. Decreased intracellular ARGs and increased extracellular ARGs further revealed that MCFAs production impaired ARGs hosts, thereby limiting the vertical gene transfer (VGT) of ARGs. Shift of microbial community combined with co-occurrence network analysis demonstrated that functional bacteria without host potential for ARGs were enriched, but potential ARGs and MGEs hosts decreased, showing the role of functional bacterial phylogeny and selection pressure of MCFAs in reducing ARGs. Finally, partial least squares path model was used to systematic verify the mechanism of ARGs removal in CE process, which was attributed to the inhibition of ARGs transmission (HGT and VGT) and shift of microbial community.

The Relationship between Quantitative Parameters of Dual-energy CT and HIF-1α Expression in Non-Small Cell Lung Cancer.

OBJECTIVE: This study aimed to investigate whether there is a correlation between quantitative parameters of dual-energy computed tomography (DECT) and the relative expression of HIF-1α in patients with non-small cell lung cancer (NSCLC) to preliminarily explore the value of DECT in evaluating the hypoxia of tumor microenvironment and tumor biological behavior and provide more information for the treatment of NSCLC. METHODS: This retrospective research included 36 patients with pathologically confirmed NSCLC who underwent dual-energy enhanced CT scans. The quantitative parameters of DECT were analyzed, including iodine concentration, water concentration, the CT values corresponding to 40keV, 70keV, 100keV, and 130keV in arterial and venous phases, and the normalized iodine concentration and the slope of the energy spectrum curve were calculated. Postoperative specimens underwent HIF immunohistochemical staining by two pathologists. Spearman correlation analysis was adopted as the statistical methodology. The data were analyzed by SPSS26.0 statistical software. RESULTS: Water concentration (r=0.659, P<0.001 and r= 0.632, P<0.001, the CT values corresponding to 100keV (r=0.645, P<0.001 and r= 0.566, P<0.001) and 130keV (r=0.687, P<0.001 and r= 0.682, P<0.001) in arterial and venous phases, and CT value of 70keV in arterial phase (r=0.457, P=0.005) were positively correlated with HIF-1α expression level. There was no correlation among iodine concentration, standardized iodine concentration, CT value of 40keV, λHU, and HIF-1α expression in arterial and venous levels (P >0.05). CONCLUSION: The quantitative parameters of DECT have a certain correlation with HIF-1α expression in NSCLC. Moreover, it has been demonstrated that DECT can be used to predict hypoxia in tumor tissues and the prognosis of lung cancer patients.

Target mediated bioreaction to engineer surface vacancy effect on Bi2O2S nanosheets for photoelectrochemical detection of FEN1.

Photoelectrochemistry represents a promising technique for bioanalysis, though its application for the detection of Flap endonuclease 1 (FEN1) has not been tapped. Herein, this work reports the exploration of creating oxygen vacancies (Ov) in situ onto the surface of Bi2O2S nanosheets via the attachment of dopamine (DA), which underlies a new anodic PEC sensing strategy for FEN1 detection in label-free, immobilization-free and high-throughput modes. In connection to the target-mediated rolling circle amplification (RCA) reaction for modulating the release of the DA aptamer to capture DA, the detection system showed good performance toward FEN1 analysis with a linear detection range of 0.001-10 U/mL and a detection limit of 1.4 × 10-4 U/mL (S/N = 3). This work features the bioreaction engineered surface vacancy effect of Bi2O2S nanosheets as a PEC sensing strategy, which allows a simple, easy to perform, sensitive and selective method for the detection of FEN1. This sensing strategy might have wide applications in versatile bioasssays, considering the diversity of a variety of biological reactions may produce the DA aptamer.

Thioredoxin Reductase-Mediated Reaction Evokes In Situ Surface Polarization Effect on BiOIO3: Toward a New Sensing Strategy for Cathodic Photoelectrochemistry.

We have witnessed the fast progress of cathodic photoelectrochemistry over the past decades, though its signal transduction tactic still lacks diversity. Exploring new sensing strategies for cathodic photoelectrochemistry is extremely demanding yet hugely challenging. This article puts forward a unique idea to incorporate an enzymatic reaction-invoked surface polarization effect (SPE) on the surface of BiOIO3 to implement an innovative cathodic photoelectrochemical (PEC) bioanalysis. Specifically, the thioredoxin reductase (TrxR)-mediated reaction produced the polar glutathione (GSH), which spontaneously coordinated to the surface of BiOIO3 and induced SPE by forming a polarized electric field, resulting in improved electron (e-) and hole (h+) pair separation efficiency and an enhanced photocurrent output. Correlating this phenomenon with the detection of TrxR exhibited a high performance in terms of sensitivity and selectivity, achieving a linear range of 0.007-0.5 µM and a low detection limit of 2.0 nM (S/N = 3). This study brings refreshing inspiration for the cathodic PEC signal transduction tactic through enzyme-mediated in situ reaction to introduce SPE, which enriches the diversity of available signaling molecules. Moreover, this study unveils the potential of in situ generated SPE for extended and futuristic applications.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept: predictive factors for the prognosis.

AIM: To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography (OCTA) in ischemic branch retinal vein occlusion (BRVO) patients with macular edema (ME) after anti-vascular endothelial growth factor (VEGF) treatment. METHODS: In this retrospective analysis, data from 60 patients (60 eyes) with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography (FFA) were studied. The eyes with ME according to spectral domain optical coherence tomography (SD-OCT) underwent intravitreal conbercept (IVC) and 3+pro re nata (PRN) regimen. The injection times were recorded. Two weeks after injection, fundus laser photocoagulation was performed in the non-perfusion area of the retina. The patients were followed up once a month for 6mo. The best-corrected visual acuity (BCVA), foveal avascular zone (FAZ), and A-circularity index (AI), at 6mo and the baseline were compared. RESULTS: All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR (P<0.001). The mean central macular thickness (CMT) significantly decreased from 476.22±163.54 to 298.66±109.23 µm. Both the FAZ area and AI at 6mo were significantly higher than those at the baseline: the FAZ area increased (0.38±0.02 vs 0.39±0.02 mm2, P<0.05); the AI increased (1.27±0.02 vs 1.31±0.01, P=0.000). The baseline BCVA showed a significantly positive correlation with the baseline FAZ area, FAZ perimeter (PERIM) and AI, final visual gain (FVG) and injection times, respectively (P<0.001). FVG showed a significantly negative correlation with the FAZ area, PERIM, AI and injection times, but a significantly positive correlation with vessel densities (VDs) 300 µm area around FAZ (FD-300; P<0.001). Injection times was positively correlated with the baseline FAZ area, and AI, but inversely correlated with the baseline FD-300 (P<0.001). However macular ischemia was noted in 5 cases during follow-up. CONCLUSION: Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment. The changes in FAZ parameters may influence the visual prognosis and injection times.

Effects of multi-gradient equilibration during vitrification on oocyte survival and embryo development in mice.

Vitrification has been widely used for oocyte cryopreservation, but there is still a need for optimization to improve clinical outcomes. In this study, we compared the routine droplet merge protocol with modified multi-gradient equilibration vitrification for cryopreservation of mouse oocytes at metaphase II. Subsequently, the oocytes were thawed and subjected to intracytoplasmic sperm injection (ICSI). Oocyte survival and spindle status were evaluated by morphology and immunofluorescence staining. Moreover, the fertilization rates and blastocyst development were examined in vitro. The results showed that multi-gradient equilibration vitrification outperformed droplet merge vitrification in terms of oocyte survival, spindle morphology, blastocyst formation, and embryo quality. In contrast, droplet merge vitrification exhibited decreasing survival rates, a reduced proportion of oocytes with normal spindle morphology, and lower blastocyst rates as the number of loaded oocytes increased. Notably, when more than six oocytes were loaded, reduced oocyte survival rates, abnormal oocyte spindle morphology, and poor embryo quality were observed. These findings highlight that the vitrification of mouse metaphase II oocytes by the modified multi-gradient equilibration vitrification has the advantage of maintaining oocyte survival, spindle morphology, and subsequent embryonic development.

Refresh Rate-Based Caching and Prefetching Strategies for Internet of Things Middleware.

One of the research directions in Internet of Things (IoT) is the field of Context Management Platforms (CMPs) which is a specific type of IoT middleware. CMPs provide horizontal connectivity between vertically oriented IoT silos resulting in a noticeable difference in how IoT data streams are processed. As these context data exchanges can be monetised, there is a need to model and predict the context metrics and operational costs of this exchange to provide relevant and timely context in a large-scale IoT ecosystem. In this paper, we argue that caching all transient context information to satisfy this necessity requires large amounts of computational and network resources, resulting in tremendous operational costs. Using Service Level Agreements (SLAs) between the context providers, CMP, and context consumers, where the level of service imperfection is quantified and linked to the associated costs, we show that it is possible to find efficient caching and prefetching strategies to minimize the context management cost. So, this paper proposes a novel method to find the optimal rate of IoT data prefetching and caching. We show the main context caching strategies and the proposed mathematical models, then discuss how a correctly chosen proactive caching strategy and configurations can help to maximise the profit of CMP operation when multiple SLAs are defined. Our model is accurate up to 0.0016 in Root Mean Square Percentage Error against our simulation results when estimating the profits to the system. We also show our model is valid using the t-test value tending to 0 for all the experimental scenarios.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum ß-EP level in puerpera. / è •è¸é’ˆæ²»ç–—äº§åŽè ¹ç—›çš„ä¸´åºŠç–—æ•ˆåŠå¯¹äº§å¦‡è¡€æ¸ ß-EP水平的影响.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.

Metformin exposure altered intestinal microbiota composition and metabolites in amphibian larvae.

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 µg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Improved sequential production of hydrogen and caproate by addition of biochar prepared from cornstalk residues.

This study proposes a new model in which ethanol and acetate produced by dark fermentation are processed by Clostridium kluyveri for chain elongation to produce caproate with an addition of biochar prepared from cornstalk residues after acid pretreatment and enzymatic hydrolysis (AERBC) in the dark fermentation and chain elongation processes. The results show a 6-25% increase in hydrogen production in dark fermentation with adding AERBC, and the maximum concentration of caproate in the new model reached 1740 mg/L, 61% higher than that in the control group. In addition, caproate was obtained by dark fermentation, using liquid metabolites as substrates with an initial pH range of 6.5-7.5. Finally, the electron balance and electron transfer efficiency in the new model were analyzed, and the role of AERBC in dark fermentation and chain elongation was investigated. This study provides a new reference for the use of dark-fermented liquid metabolites and cornstalk residue.

Bifunctional Cu(II)-containing PDA-PEI copolymer dots: Demonstration of a dual-mode platform for colorimetric-fluorescent detection of glyphosate in the environment.

The reliable and accurate detection of glyphosate is urgently demanded because it is related to food and environmental safety. In this contribution, a PDA-PEI/Cu2+ complex that possesses peroxidase-mimetic activity and stimulus-responsive fluorescence was fabricated by coordinating Cu2+ with polydopamine-polyethyleneimine copolymer dots (PDA-PEI CPDs). With the introduction of Cu2+, the fluorescence intensity of PDA-PEI CPDs dropped sharply owing to the electron transfer effect. As a peroxidase-mimicking nanozyme, the PDA-PEI/Cu2+ complex owns catalytic capacity to oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB, leading a further fluorescence quenching by internal filtering effect by oxTMB. Once the glyphosate participated, the fluorescence signal of PDA-PEI CPDs is recovered significantly because of the formation of more stable Glyp-Cu2+ complexes, meanwhile the peroxidase-mimicking activity of PDA-PEI/Cu2+ complex could be strongly hindered. According to this principle, a novel and extremely convenient 'turn off' colorimetric and 'turn on' fluorescence sensing platform can be established for dual-mode detection of glyphosate. The favorable sensitivity and selectivity and were verified in the analysis of glyphosate in the environment through the marriage of dual-signal sensing platform. The detection limit of the dual-mode glyphosate sensing platform was 103.82 ng/mL for colorimetric assay and 16.87 ng/mL for fluorescent assay, respectively. Satisfactory recoveries in the range of 96.40%-104.66% were obtained, indicating the potential of this method for application in complicated real sample. Thereby, this strategy broadens the applications of polydopamine nanomaterials and holds a promising application in determination of pesticide residues.

[Clinical characteristics of plastic bronchitis and risk factors for recurrence in children]. / å„¿ç«¥å¡‘åž‹æ€§æ”¯æ°”ç®¡ç‚Žä¸´åºŠç‰¹å¾åŠå¤å‘å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS: Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Embryonic development, hatchling performance and metabolic profile after egg exposure to environmentally relevant levels of chlorpyrifos in an aquatic turtle.

The extensive use of organophosphorus insecticides poses a threat to the survival of non-target organisms. Ecotoxicological outcomes of embryonic exposure to insecticides are rarely evaluated in various oviparous species. In this study, soft-shelled turtle (Pelodiscus sinensis) eggs were incubated in moist substrate containing different levels (0, 2, 20 and 200 µg/kg) of chlorpyrifos to investigate its toxic effects on embryonic development and survival, and hatchling physiological performance. Chlorpyrifos exposure had no significant impacts on embryonic development rate and egg survival in P. sinensis. Similarly, embryonic chlorpyrifos exposure neither obviously affected the size and locomotor performance of hatchlings, nor changed the activities of superoxide dismutase and catalase, and content of malondialdehyde in their erythrocytes. Based on liquid chromatography-mass spectrometry analysis, minor metabolic perturbations related to amino acid, lipid and energy metabolism in hatchlings after embryonic chlorpyrifos exposure were revealed by hepatic metabolite profiling. Overall, our results suggested that embryonic exposure to environmentally relevant levels of chlorpyrifos had only a limited impact on physiological performances of hatchlings, although it would result in a potential risk of hepatotoxicity in P. sinensis.

Stacked SiGe nanosheets p-FET for Sub-3 nm logic applications.

The fabrication of vertically stacked SiGe nanosheet (NS) field-effect transistors (FETs) was demonstrated in this study. The key process technologies involved in this device fabrication are low pressure chemical vapor deposition SiGe/Si multilayer epitaxy, selective etching of Si layers over SiGe layers using tetramethyl-ammonium-hydroxide wet solution, and atomic layer deposition of Y2O3 gate dielectric. For the fabricated stacked SiGe NS p-GAAFETs with a gate length of 90 nm, ION/IOFF ratio of around 5.0 × 105 and subthreshold swing of 75 mV/dec were confirmed via electrical measurements. Moreover, owing to its high quality of Y2O3 gate dielectric, the device showed a very small drain-induced barrier-lowering phenomenon. These designs can improve the gate controllability of channel and device characteristics.

[Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis].

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION: Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. METHODS: Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. RESULTS: Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1ß, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1ß, IL-18, HMGB1 and the cleaved form of GSDMD. CONCLUSIONS: Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

A chromosome-level genome assembly of Hong Kong catfish (Clarias fuscus) uncovers a sex-determining region.

BACKGROUND: Hong Kong catfish (Clarias fuscus) is an ecologically and economically important species that is widely distributed in freshwater regions of southern China. Hong Kong catfish has significant sexual growth dimorphism. The genome assembly of the Hong Kong catfish would facilitate study of the sex determination and evolution mechanism of the species. RESULTS: The first high-quality chromosome-level genome of the Hong Kong catfish was constructed. The total genome was 933.4 Mb, with 416 contigs and a contig N50 length of 8.52 Mb. Using high-throughput chromosome conformation capture (Hi-C) data, the genome assembly was divided into 28 chromosomes with a scaffold N50 length of 36.68 Mb. A total of 23,345 protein-coding genes were predicted in the genome, and 94.28% of the genes were functionally annotated in public databases. Phylogenetic analysis indicated that C. fuscus and Clarias magur diverged approximately 63.7 million years ago. The comparative genome results showed that a total of 60 unique, 353 expanded and 851 contracted gene families were identified in Hong Kong catfish. A sex-linked quantitative trait locus identified in a previous study was located in a sex-determining region of 30.26 Mb (0.02 to 30.28 Mb) on chromosome 13 (Chr13), the predicted Y chromosome. This QTL region contained 785 genes, of which 18 were identified as sex-related genes. CONCLUSIONS: This study is the first to report the chromosome-level genome assembly of Hong Kong catfish. The study provides an excellent genetic resource that will facilitate future studies of sex determination mechanisms and evolution in fish.