A novel prognostic model to predict mortality in patients with acute-on-chronic liver failure in intensive care unit.

Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.

Fluorescence detecting glycopeptide antibiotics via a dynamic molecular switch.

BACKGROUND: Glycopeptide antibiotics (GPAs) represented by vancomycin (VAN) are clinically used as a first-line treatment for serious infections caused by Gram-positive pathogens. The use and dosing methods of GPAs are rigorously managed for safety considerations, which calls for fast and accurate quantification approaches. RESULT: A new sort of fluorescent probes for GPAs has been proposed, each of which was integrated by a fluorescein-based reporter and a GPAs' recognition peptide D-alanyl-D-alanine (D-Ala-D-Ala). These probes work as dynamic molecular switches, which mainly exist as non-fluorescent spirolactam forms in the absence of GPAs. GPAs binding with the dipeptide regulates the dynamic balance between fluorescence OFF lactam form and fluorescence ON ring-opened form, rendering these probes capable of GPAs detecting. The most promising one P1 exhibits excellent sensitivity and selectivity towards GPAs detection. SIGNIFICANCE: Different to previous developments, P1 consists of a single fluorophore without the need of a fluorescence-quenching group or a secondary dye, which is the smallest fluorescent probe for GPAs up to now. P1 realizes direct VAN quantification from complex biological samples including real serums, dispensing with additional drug extraction. More interestingly, both P1 and P6 can distinguish GPAs with different peptide backbones, which has not been achieved previously.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Chronic Stress Dampens Lactobacillus Johnsonii-Mediated Tumor Suppression to Enhance Colorectal Cancer Progression.

Colorectal cancer development and outcome are impacted by modifiable risk factors, including psychologic stress. The gut microbiota has also been shown to be linked to psychologic factors. Here, we found a marked deteriorative effect of chronic stress in multiple colorectal cancer models, including chemically induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA sequencing data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed colorectal cancer group by activated ß-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on colorectal cancer progression. Stressed colorectal cancer mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC/MS-MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced colorectal cancer progression by decreasing ß-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on colorectal cancer. Altogether, these data identify that stress impacts the gut microbiome to support colorectal cancer progression. SIGNIFICANCE: Chronic stress stimulates cancer stemness by reducing the intestinal abundance of L. johnsonii and its metabolite PCA to enhance ß-catenin signaling, forming a basis for potential strategies to circumvent stress-induced cancer aggressiveness. See related commentary by McCollum and Shah, p. 645.

The Gene Expression Profiles Associated with Maternal Nicotine Exposure in the Liver of Offspring Mice.

This study aims to investigate the effect of maternal nicotine exposure on the gene expression profiles in the liver of offspring mice. Pregnant mice were subcutaneously injected with either saline vehicle or nicotine twice a day on gestational days 11-21. Total RNA from the liver samples which collected from the offspring mice of postnatal day 7 and 21 was subjected to RNA sequencing. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were conducted to identify the functions of differentially expressed genes (DEGs). Four genes were selected for further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 448 DEGs and 186 DEGs were identified on postnatal day 7 and 21, respectively. GO analysis revealed that the DEGs on postnatal day 7 mainly participated in the biological functions of cell growth and proliferation, and the DEGs on postnatal day 21 mainly participated in ion transport/activity. KEGG enrichment analysis showed that the DEGs on postnatal day 7 were mainly enriched in the cell cycle, cytokine-cytokine receptor interactions, hypertrophic cardiomyopathy, and the p53 signaling pathway, while the DEGs on postnatal day 21 were mainly enriched in neuroactive ligand-receptor interactions, the calcium signaling pathway, retinol metabolism, and axon guidance. The qRT-PCR results were consistent with the RNA sequencing data. The DEGs may affect the growth of liver in early postnatal period while may affect ion transport/activity in late postnatal period.

Dissolved organic matter accelerates microbial degradation of 17 alpha-ethinylestradiol in the presence of iron mineral.

Dissolved organic matter (DOM) and iron minerals widely existing in the natural aquatic environment can mediate the migration and transformation of organic pollutants. However, the mechanism of interaction between DOM and iron minerals in the microbial degradation of pollutants deserves further investigation. In this study, the mechanism of 17 alpha-ethinylestradiol (EE2) biodegradation mediated by humic acid (HA) and three kinds of iron minerals (goethite, magnetite, and pyrite) was investigated. The results found that HA and iron minerals significantly accelerated the biodegradation process of EE2, and the highest degradation efficiency of EE2 (48%) was observed in the HA-mediated microbial system with pyrite under aerobic conditions. Furthermore, it had been demonstrated that hydroxyl radicals (HO•) was the main active substance responsible for the microbial degradation of EE2. HO• is primarily generated through the reaction between hydrogen peroxide secreted by microorganisms and Fe(II), with aerobic conditions being more conducive. The presence of iron minerals and HA could change the microbial communities in the EE2 biodegradation system. These findings provide new information for exploring the migration and transformation of pollutants by microorganisms in iron-rich environments.

Pyroptosis is involved in maternal nicotine exposure-induced metabolic associated fatty liver disease progression in offspring mice.

We have investigated whether inflammasomes and pyroptosis are activated in maternal nicotine exposure (MNE) offspring mice and whether they are involved in MNE-promoted metabolic associated fatty liver disease (MAFLD) in adult offspring. We injected pregnant mice subcutaneously with saline vehicle or nicotine twice a day on gestational days 11-21. Offspring mice from both groups were fed with a normal diet (ND) or a high-fat diet (HFD) for 6 months at postnatal day 21 to develop the MAFLD model. Serum biochemical indices were analyzed, and liver histology was performed. The expression levels of inflammasome and pyroptosis proteins were detected by western blot. We found MNE significantly aggravated the injury of MAFLD in adult offspring mice. MNE activated inflammasomes and pyroptosis in both infant and adult offspring mice. HFD treatment activated inflammasomes but not pyroptosis at 3 months, while it showed no effect at 6 months. However, pyroptosis was more severe in MNE-HFD mice than in MNE-ND mice at 6 months. Taken together, our data suggest MNE promotes MAFLD progression in adult offspring mice. MNE also induces NLRP3 and NLRP6 inflammasome activation and pyroptosis in both infant and adult offspring mice, which may be involved in MNE-promoted progression of MAFLD.

Overexpression of miR-124 in astrocyte improves neurological deficits in rat with ischemic stroke via DLL4 modulation.

BACKGROUND: Astrocytes have been demonstrated to undergo conversion into functional neurons, presenting a promising approach for stroke treatment. However, the development of small molecules capable of effectively inducing this cellular reprogramming remains a critical challenge. METHODS: Initially, we introduced a glial cell marker gene, GFaABC1D, as the promoter within an adeno-associated virus vector overexpressing miR-124 into the motor cortex of an ischemia-reperfusion model in rats. Additionally, we administered NeuroD1 as a positive control. Lentiviral vectors overexpressing miR-124 were constructed and transfected into primary rat astrocytes. We assessed the cellular distribution of GFAP, DCX, and NeuN on days 7, 14, and 28, respectively. RESULTS: In rats with ischemic stroke, miR-124-transduced glial cells exhibited positive staining for the immature neuron marker doublecortin (DCX) and the mature neuron marker NeuN after 4 weeks. In contrast, NeuroD1-overexpressing model rats only expressed NeuN, and the positive percentage was higher in co-transfection with miR-124 and NeuroD1. Overexpression of miR-124 effectively ameliorated neurological deficits and motor functional impairment in the model rats. In primary rat astrocytes transduced with miR-124, DCX was not observed after 7 days of transfection, but it appeared at 14 days, with the percentage further increasing to 44.6% at 28 days. Simultaneously, 15.1% of miR-124-transduced cells exhibited NeuN positivity, which was not detected at 7 and 14 days. In vitro, double fluorescence assays revealed that miR-124 targeted Dll4, and in vivo experiments confirmed that miR-124 inhibited the expression of Notch1 and DLL4. CONCLUSIONS: The overexpression of miR-124 in astrocytes demonstrates significant potential for improving neurological deficits following ischemic stroke by inhibiting DLL4 expression, and it may facilitate astrocyte-to-neuronal transformation.

Effects of Exercise Training Under Hypoxia versus Normoxia on Cognitive Function in Clinical and Non-Clinical Populations: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of exercise training under hypoxia versus normoxia on cognitive function in clinical and non-clinical populations. DATA SOURCES: From inception to June 13th, 2022, a systematic search was performed on PubMed, Web of Science, Embase, Scopus, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials comparing the effects of exercise under hypoxic vs normoxic on cognition in clinical and non-clinical populations were included. The systematic search generated 14,894 relevant studies, of which 12 were finally included. DATA EXTRACTION: Two reviewers independently extracted data from included studies. Results were expressed as standardized mean difference (SMD). Each included study was assessed using the Cochrane Risk of Bias 1.0 (RoB1.0) tool. Finally, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to rate the certainty of evidence for each outcome. DATA SYNTHESIS: Overall, 12 studies with a total of 338 participants met the inclusion criteria. The pooled results suggested that hypoxia exercise had a small but not statistically significant positive effect on overall cognitive function (SMD=0.064, 95% confidence interval (CI): -0.156-0.284, P=.567, very low-certainty evidence), when compared with normoxic exercise. Regarding the domain-specific cognitive functions, there was a medium and significant positive effect on memory (SMD=0.594, 95% CI: 0.068 to 1.120, P=.027, very low-certainty evidence), while effects on visuospatial function (SMD=0.490, 95% CI: -0.030 to 1.010, P=.065, very low-certainty evidence), attention (SMD=0.037, 95% CI: -0.340 to 0.414, P=.847, very low-certainty evidence), executive function (SMD=0.096, 95% CI: -0.268 to 0.460, P=.605, very low-certainty evidence), and processing speed (SMD=-0.145, 95% CI: -0.528 to 0.239, P=.459, very low-certainty evidence) were not statistically significant. CONCLUSIONS: The current pooled results revealed that hypoxic exercise was related to improved cognitive performance. Nevertheless, exercise under hypoxia did not have a significant advantage in cognitive promotion when compared with exercise under normoxia.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

A Validated Composite Score Demonstrates Potential Superiority to MELD-Based Systems in Predicting Short-Term Survival in Patients with Liver Cirrhosis and Spontaneous Bacterial Peritonitis-A Preliminary Study.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. AIMS: This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. METHODS: Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. RESULTS: In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. CONCLUSIONS: MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.

Surface Modification of Li3VO4 with PEDOT:PSS Conductive Polymer as an Anode Material for Li-Ion Capacitors.

Li3VO4 (LVO) is a highly promising anode material for lithium-ion batteries, owing to its high capacity and stable discharge plateau. However, LVO faces a significant challenge due to its poor rate capability, which is mainly attributed to its low electronic conductivity. To enhance the kinetics of lithium ion insertion and extraction in LVO anode materials, a conductive polymer called poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is applied to coat the surface of LVO. This uniform coating of PEDOT:PSS improves the electronic conductivity of LVO, thereby enhancing the corresponding electrochemical properties of the resulting PEDOT:PSS-decorated LVO (P-LVO) half-cell. The charge/discharge curves between 0.2 and 3.0 V (vs. Li+/Li) indicate that the P-LVO electrode displays a capacity of 191.9 mAh/g at 8 C, while the LVO only delivers a capacity of 111.3 mAh/g at the same current density. To evaluate the practical application of P-LVO, lithium-ion capacitors (LICs) are constructed with P-LVO composite as the negative electrode and active carbon (AC) as the positive electrode. The P-LVO//AC LIC demonstrates an energy density of 107.0 Wh/kg at a power density of 125 W/kg, along with superior cycling stability and 97.4% retention after 2000 cycles. These results highlight the great potential of P-LVO for energy storage applications.

Effect of Multicomponent Exercise on Cognition, Physical Function and Activities of Daily Life in Older Adults With Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the evidence for the effectiveness of multicomponent exercise (an exercise program combining aerobic, endurance, balance, and flexibility exercises) on cognition, physical function, and activities of daily living in people with dementia and mild cognitive impairment (MCI). DATA SOURCES AND STUDY SELECTION: We conducted this study under the guidance of a designated protocol (PROSPERO CRD42022324641). Pertinent randomized controlled trials were selected from PubMed, Embase, Web of Science, and the Cochrane Library by 2 independent authors through May 2022. DATA EXTRACTION: Two authors independently extracted the data and assessed the quality of the included studies following the Cochrane Risk of Bias tool. Outcome data were extracted in a random effects model and estimated as Hedges' g and 95% confidence interval (CI). To validate specific results, the Egger test combined the Duval and Tweedie "trim and fill" method and sensitivity analysis with study removed were performed. DATA SYNTHESIS: A total of 21 publications were eligible for the quantitative analysis. In dementia, estimates of Hedges' g showed effects on global cognition (g=0.403; 95% CI, 0.168-0.638; P<.05), especially executive function (g=0.344; 95% CI, 0.111-0.577; P<.05), flexibility (g=0.671; 95% CI, 0.353-0.989; P<.001), agility and mobility (g=0.402; 95% CI, 0.089-0.714; P<.05), muscle strength (g=1.132; 95% CI, 0.420-1.845; P<.05), and activities of daily living (g=0.402; 95% CI, 0.188-0.615; P<.05). Also, a positive trend was observed in gait speed. Additionally, multicomponent exercise had positive effects on global cognition (g=0.978; 95% CI, 0.298-1.659; P<.05) and executive function (g=0.448; 95% CI, 0.171-0.726; P<.05) in patients with MCI. CONCLUSIONS: Our findings confirm the viability of multicomponent exercise as a management strategy for patients with dementia and MCI.

Beta-adrenergic receptor blocker propranolol triggers anti-tumor immunity and enhances irinotecan therapy in mice colorectal cancer.

Colorectal cancer (CRC) stands as the second leading cause of cancer-related deaths worldwide with limited available medicines. While drug repurposing comes as a promising strategy for cancer treatment, we discovered that propranolol (Prop), a non-selective ß1 and ß2 adrenergic receptor blocker, significantly inhibited the development of subcutaneous CT26 CRC and AOM/DSS-induced CRC models. The RNA-seq analysis highlighted the activated immune pathways after Prop treatment, with KEGG analysis enriched in T-cell differentiation. Routine analyses of blood revealed a decrease in neutrophil to lymphocyte ratio, a biomarker of systemic inflammation, and a prognostic indicator in the Prop-treated groups in both CRC models. Analysis of the tumor-infiltrating immune cells exhibited that Prop regressed the exhaustion of CD4+ and CD8+ T cells in the CT26-derived graft models, which was further corroborated in the AOM/DSS-induced models. Furthermore, bioinformatic analysis fitted well with the experimental data, showing that ß2 adrenergic receptor (ADRB2) was positively correlated with T-cell exhaustion signature in various tumors. The in vitro experiment showed no direct effect of Prop on CT26 cell viability, while T cells were activated with significantly-upregulated production of IFN-γ and Granzyme B. Consistently, Prop was unable to restrain CT26 tumor growth in nude mice. At last, the combination of Prop and the chemotherapeutic drug Irinotecan acted out the strongest inhibition in CT26 tumor progress. Collectively, we repurpose Prop as a promising and economical therapeutic drug for CRC treatment and highlight T-cell as its target.

The Ratio of Clavicle Length to Head Circumference: A Novel Date-Independent Clavicle Index.

ABSTRACT: We aimed to plot the growth curve of the fetal clavicle, identify gestational date-independent parameters. Using 2-dimensional ultrasonography, we obtained the clavicle lengths (CLs) from 601 normal fetuses between 12 and 40 gestational age (GA). The CL/fetal growth parameters ratio was calculated. Moreover, 27 cases of fetal growth restriction (FGR) and 9 cases of small for GA (SGA) were detected. In normal fetuses, the mean CL (mm) = -68.2 + 29.80 × ln(GA) ± Z × (1.07 + 0.02 × GA). A linear relationship was detected between CL and head circumference (HC), biparietal diameter, abdominal circumference and femoral length with R2 values of 0.973, 0.970, 0.962, and 0.972, respectively. The CL/HC ratio (mean value 0.130) showed no significant correlation with GA. Clavicle lengths in the FGR group significantly decreased compared with the SGA group ( P < 0.01). This study determined a reference range of fetal CL in a Chinese population. Furthermore, the CL/HC ratio, which is independent of GA, is a novel parameter for the evaluation of the fetal clavicle.

Antioxidant, anticancer activity and molecular docking study of lycopene with different ratios of Z-isomers.

The main purpose of this study was to compare the antioxidant and anticancer activities of lycopene samples with different ratios of Z-isomers. Lycopene samples containing 5%, 30%, and 55% Z-isomers were successfully prepared by using thermal treatment combined with anti-solvent crystallization. The in vitro bio-accessibility of lycopene was estimated by the determination of partition factor (PF) and the results showed that lycopene with 55% Z-isomers possessed the highest bio-accessibility. Moreover, DPPH and ABTS assays suggested that the antioxidant activity of lycopene increased with the Z-isomers content from 5% to 55%. However, lycopene inhibited the survival of human hepatocellular carcinoma cells (HepG2) in a dose and time-dependent manner. The highest inhibition of HepG2 cell lines was achieved by 55% Z-ratio of lycopene. The cell viability was 22.54% at 20 µg/mL after incubating for 24 h, the number of cells was significantly reduced and the morphology was shrunk. Furthermore, molecular docking was introduced to compare the binding ability between different lycopene isomers with Scavenger Receptor class B type I (SR-BI), and the results revealed that the affinity of (all-E)-lycopene with SR-BI was lower compared to 5Z-lycopene and 13Z-lycopene, providing the reasons for different bioavailability of the above-mentioned lycopene isomers. All the above results demonstrated that Z-isomers-rich lycopene could enhance bio-accessibility and biological functionality.

Synthesis of Quercetin-Acid Esters and Its Reduction of H2 O2 -Triggered PC12 Cells Damage by Down-Regulating ROS.

Quercetin is a kind of polyphenolic flavonoid compounds which has perfect antioxidant properties. However, quercetin is not available in many situations due to its poor bioavailability. In this work, the QAEs with better solubility and even stronger antioxidant properties were synthesized, through the esterification between quercetin and the chlorinated cinnamic acid or its derivatives, whose chlorination were achieved by using SOCl2 . The protective effects of the QAEs were evaluated by the H2 O2 -induced apoptosis experiment in rat adrenal pheochromocytoma cells (PC12 cells) and its ability to remove ROS generated by oxidative stress. Compared with the original quercetin group, the QAEs groups showed much improved cell viability and capability of removing ROS, which means their higher bioavailability than the parent.

TRPC absence induces pro-inflammatory macrophages and gut microbe disorder, sensitizing mice to colitis.

The transient receptor potential canonical (TRPC) channels, encoded in seven non-allelic genes, are important contributors to calcium fluxes, are strongly associated with various diseases. Here we explored the consequences of ablating all seven TRPCs in mice focusing on colitis. We discovered that absence of all seven TRPC proteins in mice (TRPC HeptaKO mice) promotes the development of dextran sulfate sodium (DSS)-induced colitis. RNA-sequence analysis highlighted an extremely pro-inflammatory profile in colons of DSS-treated TRPC HeptaKO mice, with an amount of increased pro-inflammatory cytokines and chemokines. Flow cytometry analysis showed that the infiltration of Ly6Chi monocytes and neutrophils in colonic lamina propria was significantly increased in DSS-treated TRPC HeptaKO mice. Results also revealed that macrophages from TRPC HeptaKO mice exhibited M1 polarization and enhanced secretion of pro-inflammatory factors. In addition, the composition of gut microbiota was markedly disturbed in DSS-treated TRPC HeptaKO mice. However, upon antibiotic cocktail (Abx)-treatment, TRPC HeptaKO mice showed no significant differences with WT mice in disease severity. Collectively, these data suggest that ablation of all TRPCs promotes the development of DSS-induced colitis by inducing pro-inflammatory macrophages and gut microbiota disorder.

Mucinous Adenocarcinoma of the Lung Diagnosed by Radial Endobronchial Ultrasound-guided Bronchoscopic Cryobiopsy and Presenting as Interstitial Lung Disease in a Patient with Systemic Sclerosis.

We report a patient with systemic sclerosis who was diagnosed with advanced-stage mucinous adenocarcinoma of the lungs. The clinical presentation, imaging findings, pathological results, and molecular diagnoses are presented. A 64-year-old woman with systemic sclerosis was administered prednisolone and hydroxychloroquine sulfate to control her disease. High-resolution computed tomography (HRCT) revealed an interstitial pattern in both lungs during annual imaging. Connective tissue disease-associated interstitial lung disease (CTD-ILD) was diagnosed using blood tests, pulmonary function tests, and imaging findings. One year later, the patient underwent follow-up chest HRCT, which showed progressive lung disease. The patient underwent endobronchial ultrasound (EBUS)-guided transbronchial lung cryobiopsy and computed tomography-guided biopsy for a pathological diagnosis. The pathology reports of bilateral lungs disclosed mucinous adenocarcinoma. After tumor staging and mutation testing, the patient received chemotherapy with pemetrexed and cisplatin. The bilateral lung lesions subsided after four cycles of first-line chemotherapy. Patients with CTD and lung involvement may be diagnosed with CTD-ILD. Although histopathological results are not mandatory for ILD diagnosis, EBUS-guided transbronchial lung biopsy or lung cryobiopsy should be considered when ILD has atypical or unexplained features.

Double-to-Single Umbilical Artery With a Low Pulsatility Index Leading to Fetal Death: A Case Report and Review of Literature.

Single umbilical artery (SUA) may be associated with adverse pregnancy outcomes, such as fetal death, emergency cesarean section, premature delivery, small-for-gestational-age infants, and admission to neonatal intensive care unit, and some SUAs are transformed from originally double umbilical arteries (UA). The pulsatility index (PI) can reflect the resistance of UA, and clinicians attach importance to high PI but easily overlook low levels of it. We reported one case of a pregnant woman who underwent double to single UA accompanied by low UA-PI and finally had intrauterine fetal death. Additionally, the literature regarding SUA and UA-PI is reviewed. This study aims to alert clinicians to the risk of double-to-single UA with low UA-PI and strengthen fetal monitoring and timely intervention. We look forward to more clinical evidence to investigate it.