Dietary nitrate maintains homeostasis of oxidative stress and gut microbiota to promote flap survival in type 2 diabetes mellitus rats.

BACKGROUND: Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. METHODS: This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. RESULTS: Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. CONCLUSION: Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM.

A Mesenteric Fat-Derived Radiomic Model to Identify Colonic Fibrosis and Predict Treatment Response to Biologics in Chronic Ulcerative Colitis.

BACKGROUND: Evidence suggested the lesion of ulcerative colitis stretches beyond mucosa. The application of radiomics on ulcerative colitis fibrosis is unclear. OBJECTIVE: We aimed to characterize the colonic fibrosis and treatment response to biologics in chronic ulcerative colitis using radiomic features extracted from bowel wall and mesenteric adipose tissue. DESIGN: Retrospective analysis of prospective database. SETTINGS: This study was conducted in a single tertiary center. PATIENTS: A total of 72 patients who underwent proctocolectomy and 47 patients who received biologics induction were included. INTERVENTION: Computed Tomography images were collected and radiomic features were extracted to develop radiomic models using logistic regression. MAIN OUTCOME MEASURES: Main outcome was colonic fibrosis, which was classified into mild and severe based on histological scoring. RESULTS: The area under curve of the bowel wall model to predict severe fibrosis was 0.931 (p < 0.001) and 0.869 (p < 0.001) in the training and test cohort, respectively. For mesenteric adipose tissue model, area under curve was 0.947 (p < 0.001) and 0.837 (p < 0.001), respectively. The mesenteric adipose tissue model was superior to bowel wall model (area under curve, 0.809, p < 0.001 and 0.722, p = 0.006) in predicting response to biologics in chronic ulcerative colitis. LIMITATIONS: Retrospective single center study. CONCLUSIONS: Two radiomic models derived from bowel wall and mesenteric adipose tissue features readily predicted colonic fibrosis and treatment response of biologics in chronic ulcerative colitis. The mesentery harbors critical information and was essentially involved in fibrogenesis. See Video Abstract.

Impact of bone marrow fibrosis on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.

Vulnerability and driving mechanism of four typical grasslands in China under the coupled impacts of climate change and human activities.

Understanding of how different grasslands types respond to climate change and human activities across different spatial and temporal dimensions is crucial for devising effective strategies to prevent grasslands degradation. In this study, we developed a novel vulnerability assessment model for grasslands that intricately evaluates the combined impact of climate change and human activities. We then applied this model to analyze the vulnerability and driving mechanism of four representative Chinese grasslands to climate change and human activities. Our findings indicate that the vulnerability of the four grasslands would show a pattern of higher in the west and lower in the east under the influence of climate change alone. However, when human activities are factored in, the vulnerability across the four grasslands tends to homogenize, with human activities notably reducing the vulnerability of alpine grasslands in the west and, conversely, increasing the vulnerability of grasslands in the east. Furthermore, our study reveals distinct major environmental drivers of grasslands vulnerability across different regions. The two western alpine grasslands exhibit higher vulnerability to annual mean temperature and isothermality compared to the eastern temperate grasslands, while their vulnerability to precipitation of the coldest quarter is lower than that of the eastern temperate grasslands. These findings are helpful for understanding the multifaceted causes and mechanisms of grasslands degradation, providing a scientific foundation for the sustainable management and conservation of grassland resources.

Carboxypeptidase inhibitor Latexin (LXN) regulates intestinal organogenesis and intestinal remodeling involved in intestinal injury repair in mice.

The self-renewal and regeneration of intestinal epithelium are mainly driven by intestinal stem cells resided in crypts, which are crucial for rapid recovery intestinal tissue following injury. Latexin (LXN) is a highly expressed stem cell proliferation and differentiation related gene in intestinal tissue. However, it is still ambiguous whether LXN participates in intestine regeneration by regulating intestinal stem cells (ISCs). Here, we report that LXN colocalizes with Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in intestinal crypts, and deletion of LXN upregulates the expression of Lgr5 in intestinal crypts. LXN deficiency promotes the proliferation of ISCs, thereby enhances the development of intestinal organoids. Mechanically, we show that LXN deficiency enhances the expression of Lgr5 in ISCs by activating the Yes-associated protein (YAP) and wingless (Wnt) signal pathways, thus accelerating intestinal normal growth and regeneration post-injury. In summary, these findings uncover a novel function of LXN in intestinal regeneration post-injury and intestinal organogenesis, suggesting the potential role of LXN in the treatment of inflammatory bowel diseases.

Associations of childhood and adulthood body size, and child-to-adult body size change with adult telomere length.

AIM: To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). METHODS: We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). RESULTS: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. CONCLUSIONS: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.

WT1 gene mutations impact post-transplant relapse in myelodysplastic syndrome with excess blasts 2 patients.

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

Prophylactic therapy using epigenetic agents for RUNX1::RUNXT1-positive high-risk AML after Allo-HSCT.

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

Association of exposure to multiple metals with hemoglobin levels in Chinese children and adolescents.

BACKGROUND: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS: The multivariable-adjusted ß-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted ß = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.

A computed tomography-based nomogram for neoadjuvant chemotherapy plus immunotherapy response prediction in patients with advanced esophageal squamous cell carcinoma.

Objective: To develop a CT-based nomogram to predict the response of advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemotherapy plus immunotherapy. Methods: In this retrospective study, 158 consecutive patients with advanced ESCC receiving contrast-enhanced CT before neoadjuvant chemotherapy plus immunotherapy were randomized to a training cohort (TC, n = 121) and a validation cohort (VC, n = 37). Response to treatment was assessed with response evaluation criteria in solid tumors. Patients in the TC were divided into the responder (n = 69) and non-responder (n = 52) groups. For the TC, univariate analyses were performed to confirm factors associated with response prediction, and binary analyses were performed to identify independent variables to develop a nomogram. In both the TC and VC, the nomogram performance was assessed by area under the receiver operating characteristic curve (AUC), calibration slope, and decision curve analysis (DCA). Results: In the TC, univariate analysis showed that cT stage, cN stage, gross tumor volume, gross volume of all enlarged lymph nodes, and tumor length were associated with the response (all P < 0.05). Binary analysis demonstrated that cT stage, cN stage, and tumor length were independent predictors. The independent factors were imported into the R software to construct a nomogram, showing the discriminatory ability with an AUC of 0.813 (95% confidence interval: 0.735-0.890), and the calibration curve and DCA showed that the predictive ability of the nomogram was in good agreement with the actual observation. Conclusion: This study provides an accurate nomogram to predict the response of advanced ESCC to neoadjuvant chemotherapy plus immunotherapy.

Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges.

The establishment of reliable human brain models is pivotal for elucidating specific disease mechanisms and facilitating the discovery of novel therapeutic strategies for human brain disorders. Human induced pluripotent stem cell (iPSC) exhibit remarkable self-renewal capabilities and can differentiate into specialized cell types. This makes them a valuable cell source for xenogeneic or allogeneic transplantation. Human-mouse chimeric brain models constructed from iPSC-derived brain cells have emerged as valuable tools for modeling human brain diseases and exploring potential therapeutic strategies for brain disorders. Moreover, the integration and functionality of grafted stem cells has been effectively assessed using these models. Therefore, this review provides a comprehensive overview of recent progress in differentiating human iPSC into various highly specialized types of brain cells. This review evaluates the characteristics and functions of the human-mouse chimeric brain model. We highlight its potential roles in brain function and its ability to reconstruct neural circuitry in vivo. Additionally, we elucidate factors that influence the integration and differentiation of human iPSC-derived brain cells in vivo. This review further sought to provide suitable research models for cell transplantation therapy. These research models provide new insights into neuropsychiatric disorders, infectious diseases, and brain injuries, thereby advancing related clinical and academic research.

Genomic alteration discordance in the paired primary-recurrent ovarian cancers: based on the comprehensive genomic profiling (CGP) analysis.

PURPOSE: Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status. MATERIALS AND METHODS: A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne®CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors. RESULTS: By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r2 = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6. CONCLUSION: The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.

Effects of Ambient Noise Isolation on Illness Severity and Mental Health Among Hospitalized Children with Asthma: Retrospective Study.

OBJECTIVE: This study investigated the effects of ambient noise isolation on disease severity and mental health among hospitalized children with asthma. METHODS: A retrospective analysis was conducted on the clinical data of 187 hospitalized children with asthma admitted from May 2021 to May 2023. Among them, 92 cases were categorized in the control group (conventional management) and 95 in the observation group (environmental noise isolation). Ambient noise level, disease severity, mental health, and sleep quality were observed and compared between the two groups. RESULTS: Weekly time, the noise value of the observation group was lower than that of the control group (P < 0.05). Before the management, modified Tal scoring system, cough symptom score, and Spence Children's Anxiety Scale-Short Version (SCAS-S) were recorded. SCAS-S and Sleep Disturbance Scale for Children (SDSC) had no significant difference (P > 0.05). Weekly time, no differences in the score of social fear dimension of SCAS-S, score of excessive sweating dimension of SDSC, Tal score, and cough symptom score were found between the observation and control groups (P > 0.05). The scores of other dimensions of SCAS-S and SDSC were lower in the observation group than those in the control group (P < 0.05). CONCLUSIONS: Environmental noise isolation for hospitalized children with asthma can effectively improve their mental health and sleep status, but this strategy cannot improve their disease.

Peripheral CD8+PD-1+ T cells as novel biomarker for neoadjuvant chemoimmunotherapy in humanized mice of non-small cell lung cancer.

Neoadjuvant immunotherapy has shown promising clinical activity in the treatment of early non-small cell lung cancer (NSCLC); however, further clarification of the specific mechanism and identification of biomarkers are imperative prior to implementing it as a daily practice. The study investigated the reprogramming of T cells in both tumor and peripheral blood following neoadjuvant chemoimmunotherapy in a preclinical NSCLC mouse model engrafted with a human immune system. Samples were also collected from 21 NSCLC patients (Stage IA-IIIB) who received neoadjuvant chemoimmunotherapy, and the dynamics of potential biomarkers within these samples were measured and further subjected to correlation analysis with prognosis. Further, we initially investigated the sources of the potential biomarkers. We observed in the humanized mouse model, neoadjuvant chemoimmunotherapy could prevent postoperative recurrence and metastasis by increasing the frequency and cytotoxicity of CD8+ T cells in both peripheral blood (p < 0.001) and tumor immune microenvironment (TIME) (p < 0.001). The kinetics of peripheral CD8+PD-1+ T cells reflected the changes in the TIME and pathological responses, ultimately predicting survival outcome of mice. In the clinical cohort, patients exhibiting an increase in these T cells post-treatment had a higher rate of complete or major pathological response (p < 0.05) and increased immune infiltration (p = 0.0012, r = 0.792). We identified these T cells originating from tumor draining lymph nodes and subsequently entering the TIME. In conclusion, the kinetics of peripheral CD8+PD-1+ T cells can serve as a predictor for changes in TIME and optimal timing for surgery, ultimately reflecting the outcomes of neoadjuvant chemoimmunotherapy in both preclinical and clinical setting.

PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone.

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

Construction of efficient and environmentally friendly bio-based flame retardant cotton fabric through layer by layer self-assembly of alkylammonium functional silsesquioxane/phosphorylated sodium alginate.

As an important source of green cleaning flame retardants, bio-based materials have been widely studied by researchers. However, the development of efficient biobased flame retardants and convenient finishing methods was of great significance for the functional finishing of materials. Herein, a convenient and efficient flame retardant cotton fabric was prepared via layer by layer self-assembly (LbL) by alternating precipitation of a novel bio-based flame retardant phosphorylated sodium alginate (PSA) and alkylammonium functionalized siloxane (A-POSS). The effect of coating number on flame retardancy and thermal properties of coated cotton fabric was systematically studied. Thermogravimetric analysis (TGA) results showed that residual char contents of AP/PS-15BL under air and N2 atmospheres increased by 252.0% and 225.2%, respectively, compared with control cotton. In vertical flammability tests, both the AP/PS-10BL and AP/PS-15BL showed self-extinguishing behavior and successfully passed the UL-94 V-0 rating. More importantly, the LOI value of AP/PS-15BL was significantly increased to 35.0% from 20.0% of pure cotton fabric. Additionally, coated samples showed good mechanical properties and washable resistance. In CONE test, the peak heat release rate (PHRR) and total heat release rate (THR) of AP/PS-15BL decreased by 89.3% and 49.3% respectively, compared with control cotton. Therefore, this green and convenient flame-retardant finishing method has great application potential in the multi-functional finishing of cotton fabrics.

Enantioselective α-Trifluoromethylthiolation of Carbonyl Compounds with AgSCF3 and Trichloroisocyanuric Acid.

We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.

Bone Marrow Mesenchymal Stem Cells-derived Exosomes Promote Survival of Random Flaps in Rats through Nrf2-mediated Antioxidative Stress.

BACKGROUND: Random flaps are the most used defect repair method for head and neck tumors and trauma plastic surgery. The distal part of the flap often undergoes oxidative stress (OS), ultimately leading to flap necrosis. Stem cells' exosomes exhibit potential effects related to anti-inflammatory, regenerative, and antioxidant properties. Nuclear factor erythroid-2-related factor 2 (Nrf2) is an important factor in regulating oxidative balance. Exosomes have been reported to monitor its transcription to alleviate OS. This study examined the impacts and underlying mechanisms of antioxidant actions of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) on random flaps. METHODS: BMSCs-Exo were injected into the tail veins of rats on days 0, 1, and 2 after surgery of random flaps. The rats were euthanized on day 3 to calculate the survival rate. Immunohistochemical staining, western blotting, dihydroethidium probe, superoxide dismutase, and malondialdehyde assay kits were used to detect the OS level. Human umbilical vein endothelial cells were cocultured with BMSCs-Exo and ML385 (an inhibitor of Nrf2) in vitro. RESULTS: BMSCs-Exo may significantly improve the survival rate of the random flaps by reducing apoptosis, inflammation, and OS while increasing angiogenesis. Besides, BMSCs-Exo can also increase mitochondrial membrane potential and reduce reactive oxygen species levels in vitro. These therapeutic effects might stem from the activation of the Kelch-like enyol-CoA hydratase (ECH)-associated protein 1 (Keap1)/Nrf2 signaling pathway. CONCLUSION: BMSCs-Exo improved the tissue antioxidant capacity by regulating the Keap1/Nrf2 signaling pathway. BMSCs-Exo may be a new strategy to solve the problem of random flap necrosis.

Ultrasound-based deep learning radiomics model for differentiating benign, borderline, and malignant ovarian tumours: a multi-class classification exploratory study.

BACKGROUND: Accurate preoperative identification of ovarian tumour subtypes is imperative for patients as it enables physicians to custom-tailor precise and individualized management strategies. So, we have developed an ultrasound (US)-based multiclass prediction algorithm for differentiating between benign, borderline, and malignant ovarian tumours. METHODS: We randomised data from 849 patients with ovarian tumours into training and testing sets in a ratio of 8:2. The regions of interest on the US images were segmented and handcrafted radiomics features were extracted and screened. We applied the one-versus-rest method in multiclass classification. We inputted the best features into machine learning (ML) models and constructed a radiomic signature (Rad_Sig). US images of the maximum trimmed ovarian tumour sections were inputted into a pre-trained convolutional neural network (CNN) model. After internal enhancement and complex algorithms, each sample's predicted probability, known as the deep transfer learning signature (DTL_Sig), was generated. Clinical baseline data were analysed. Statistically significant clinical parameters and US semantic features in the training set were used to construct clinical signatures (Clinic_Sig). The prediction results of Rad_Sig, DTL_Sig, and Clinic_Sig for each sample were fused as new feature sets, to build the combined model, namely, the deep learning radiomic signature (DLR_Sig). We used the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) to estimate the performance of the multiclass classification model. RESULTS: The training set included 440 benign, 44 borderline, and 196 malignant ovarian tumours. The testing set included 109 benign, 11 borderline, and 49 malignant ovarian tumours. DLR_Sig three-class prediction model had the best overall and class-specific classification performance, with micro- and macro-average AUC of 0.90 and 0.84, respectively, on the testing set. Categories of identification AUC were 0.84, 0.85, and 0.83 for benign, borderline, and malignant ovarian tumours, respectively. In the confusion matrix, the classifier models of Clinic_Sig and Rad_Sig could not recognise borderline ovarian tumours. However, the proportions of borderline and malignant ovarian tumours identified by DLR_Sig were the highest at 54.55% and 63.27%, respectively. CONCLUSIONS: The three-class prediction model of US-based DLR_Sig can discriminate between benign, borderline, and malignant ovarian tumours. Therefore, it may guide clinicians in determining the differential management of patients with ovarian tumours.