Dioscin decreases M2 polarization via inhibiting a positive feedback loop between RBM47 and NF-κB in glioma.

BACKGROUND: The role of the glioblastoma (GBM) microenvironment is pivotal in the development of gliomas. Discovering drugs that can traverse the blood-brain barrier and modulate the tumor microenvironment is crucial for the treatment of GBM. Dioscin, a steroidal saponin derived from various kinds of plants and herbs known to penetrate the blood-brain barrier, has shown its powerful anti-tumor activity. However, little is known about its effects on GBM microenvironment. METHODS: Bioinformatics analysis was conducted to assess the link between GBM patients and their prognosis. Multiple techniques, including RNA sequencing, immunofluorescence staining, Western blot analysis, RNA-immunoprecipitation (RIP) assays, and Chromatin immunoprecipitation (CHIP) analysis were employed to elucidate the mechanism through which Dioscin modulates the immune microenvironment. RESULTS: Dioscin significantly impaired the polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages in vitro and in vivo. A strong correlation between high expression of RBM47 in GBM and a detrimental prognosis for patients was demonstrated. RNA-sequencing analysis revealed an association between RBM47 and the immune response. The inhibition of RBM47 significantly impaired the recruitment and polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages. Moreover, RBM47 could stabilize the mRNA of inflammatory genes and enhance the expression of these genes by activating the NF-κB pathway. In addition, NF-κB acts as a transcription factor that enhances the transcriptional activity of RBM47. Notably, we found that Dioscin could significantly inhibit the activation of NF-κB and then downregulate the expression of RBM47 and inflammatory genes protein. CONCLUSION: Our study reveals that the positive feedback loop between RBM47 and NF-κB could promote immunosuppressive microenvironment in GBM. Dioscin effectively inhibits M2 polarization in GBM by disrupting the positive feedback loop between RBM47 and NF-κB, indicating its potential therapeutic effects in GBM treatment.

A comparison of milk fat globule membranes and whey proteomes: New insight into variation nutrient differences between Buffalo, Cow, Goat, and Yak.

In this study, the whey and milk fat globule membrane (MFGM) proteomes of buffalo, cow, goat, and yak milk were analyzed using label-free proteomic technology. Totally, 1,292 MFGM proteins and 686 whey proteins were identified from these four species, and GO analysis revealed there were specific proteins with different functions in both whey (376) and MFGM (982) proteomes. The principal component analysis showed that ALB, TF, CSN1S1, and GLYCAM1 are characteristic markers of the milk for each of the four species. Furthermore, the conserved and differential in the expression of whey and MFGM proteins across the four species were identified by limma, and subsequent KEGG pathway analysis showed that immune-related proteins are both conserved and species-specific in the four species. These results provide a deepening of the understanding of the characteristics of proteins in whey and MFGMs from these four common dairy animals and new insight into developing dairy production.

The status of the global food waste mitigation policies: experience and inspiration for China.

Food waste has become a significant challenge faced by the community with a shared future for mankind, and it has also caused a considerable impact on China's food security. Scholars across disciplines, international organizations, and especially policymakers are increasingly interested in food waste. Policies are seen as a powerful factor in reducing food waste, but current research on related policies is more scattered. This paper summarizes and analyzes the experiences of food waste policy development and implementation by systematically reviewing the studies on food waste reduction policies. The results of this paper's analysis show that current global food waste policies are focused at the national strategic level, with approaches such as legislation, food donation, waste recycling, awareness and education, and data collection. At the same time, we find that the current experience of developed countries in policy formulation and implementation is beneficial for policy formulation in developing countries. And taking China as an example, we believe that developing countries can improve food waste policies in the future by improving legislation, guiding the development of food banks, promoting social governance, and strengthening scientific research projects. These policies will all contribute strongly to global environmental friendliness. In addition, we discuss some of the factors that influence the development of food waste policies and argue that in the future, more consideration needs to be given to the effects of policy implementation and that case studies should focus more on developing countries. This will contribute to the global sustainable development process. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-023-03132-0.

Gracillin relieves pulmonary fibrosis by suppressing the STAT3 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management. AIM OF THE STUDY: This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin. METHODS: We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-ß1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo, and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3. RESULTS: We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-ß1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, α-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells. CONCLUSIONS: Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF.

Focused liquid ultrasonography in dropsy protocol for quantitative assessment of subcutaneous edema.

BACKGROUND: Although subcutaneous edema is a common symptom of critically ill patients, it is still underreported due to the lack of a systematic method for evaluating it. The present study aims to describe the occurrence and distribution of subcutaneous edema, as well as the risk factors associated with it, in critically ill patients using the focused liquid ultrasonography in dropsy (FLUID) protocol, and to assess their impact on ICU mortality. METHODS: The FLUID protocol and the pitting test were performed on general ICU patients in China. Cohen's Kappa coefficient and Bland-Altman plots were used to evaluate the agreement between the two methods at each measurement site and between the whole-body subcutaneous edema scores, respectively, while a repeated measures ANOVA was performed to compare the differences between the two methods in whole-body and body-part measurements. A generalized linear model was used to evaluate the risk factors for subcutaneous edema development and the relationship between subcutaneous edema severity and ICU mortality. RESULTS: A total of 145 critically ill patients were evaluated using both approaches, of whom 40 (27.6%) experienced subcutaneous edema. Over 1440 measurements, it was found that ultrasound discovered more subcutaneous edema than the pitting test (ultrasound: 522[36.3%], pitting test: 444[30.8%], χ2 = 9.477, p = 0.002). The FLUID protocol scored edema severity significantly higher than the pitting test in the whole body and specific body parts, including the abdominal wall, thighs, chest wall, and hands. Subcutaneous edema exhibited gravity-dependent distribution patterns, particularly in the abdominal wall. The APACHE II, NT-proBNP, serum creatinine, and sepsis were independent risk factors for subcutaneous edema development. The score of ultrasonic subcutaneous edema was related to ICU mortality. CONCLUSIONS: The FLUID protocol provides a comprehensive strategy for the semi-quantitative assessment of subcutaneous edema in critically ill patients. In detecting the onset and severity of edema, ultrasound was found to outperform the pitting test. Subcutaneous edema showed a gravity-dependent distribution pattern, and its severity was associated with mortality.

Pollution Characteristics, Spatial Distribution, and Evaluation of Heavy Metal(loid)s in Farmland Soils in a Typical Mountainous Hilly Area in China.

Heavy metal(loid)s pollution in farmland soil is not only a serious environmental but also a human health-related issue. Accurate understanding and evaluation of heavy metal pollution levels in the soil are very important for sustainable agricultural development and food safety. Mountainous and hilly areas have the dual functions of industrial development and agricultural production, and the farmland soil in these areas is more susceptible to heavy metal pollution. In this study, the single factor index, Nemerow index, geo-accumulation index, enrichment factor index, and potential ecological risk indices, which are mainly used to assess the contamination and risk of heavy metals in farmland soils. The sources of heavy metals in agricultural soils of the study area were analyzed using correlation analysis and principal component analysis. Finally, geostatistical methods were used to map the heavy metal contamination of farmland soils. An average concentration of all heavy metals (except As) in farmland soils of the study area exceeded the corresponding background values, as indicated by the obtained results. The results of the principal component analysis showed that the heavy metal sources in the soils of the study area can be classified into two groups. The five pollutant index methods all showed the most serious Hg pollution in the study area. The integrated pollutant mapping results showed that the risk of heavy metal pollution in the study area was mostly moderate, except for the western and central parts of the region. This study enhances understanding of the pollution levers of heavy metals in Yiyuan farmland soils, and also can facilitate the monitoring of heavy metal contaminants at the primary stage of the food chain and assess the risk of the presence of heavy metal contaminants in food, thus improving the health of the residents.

Lysine-40 succinylation of TAGLN2 induces glioma angiogenesis and tumor growth through regulating TMSB4X.

Protein lysine succinylation (Ksucc) represents an important regulatory mechanism of tumor development. In this work, the difference of protein Ksucc between HCMEC/D3 co-cultured with U87 (glioma endothelia cells, GEC) and without U87 (normal endothelia cells, NEC) was investigated using TMT labeling and affinity enrichment followed by high-resolution LC-MS/MS analysis. Interestingly, TAGLN2 was highly succinylated at K40 in GEC (15.36 folds vs. NEC). Compared to the Vector group, TAGLN2WT and a succinylation-mimetic TAGLN2K40E greatly promoted the angiogenesis of glioma in vitro and in vivo. Furthermore, the adhesion and metastasis of U87 co-cultured with GEC in the TAGLN2WT or TAGLN2K40E group were also significantly promoted. This was consistent with the increased expression of VE-cadherin and actin cytoskeleton remodeling induced by TAGLN2 K40succ in GEC. In addition, high K40succ of TAGLN2 was associated with poor prognosis in patients with glioma. Overexpression of TAGLN2K40E also markedly promoted the proliferation and migration of glioma cells, further analysis of in vivo xenograft tumors showed that there was a significant decrease in tumor size and angiogenesis in the TAGLN2K40R group. Notably, the co-localization of TMSB4X and TAGLN2 mainly in the nucleus and cytoplasm of glioma cells was detected by immunofluorescence staining. We identified TMSB4X as a potential target of TAGLN2, which was proved to interact with TAGLN2WT rather than TAGLN2K40A. And the inhibition of TMSB4X could markedly attenuate the proliferation and migration of glioma cells induced by TAGLN2 K40succ. The results revealed K40succ of TAGLN2 could be a novelty diagnosis and therapeutic target for gliomas.

Bibliometric analysis of hypoxia inducible factor prolyl hydroxylase inhibitor in anemia.

Objective: This study aimed to explore the global research status, hot topics, and future prospects in the field of the hypoxia inducible factor prolyl hydroxylase inhibitor (HIF-PHI) by bibliometric analysis. Methods: The literatures about HIF-PHI were downloaded from the Web of Science Core Collection and Pubmed database from inceptions to January.10th. 2022. The VOSviewer 1.6.18 was used to explore the bibliometric networks and research priorities of HIF-PHI. Results: A total of 409 papers about HIF-PHI were included, involving 1,674 authors from 548 institutions in 43 countries. The number of HIF-PHI literatures showed an upward trend, with steady growth from 2016 to 2020 and rapid growth in 2021. Tadao Akizawa, Masaomi Nangaku and Alexander R Cobitz published the most literatures. The United States, Japan and China contributed the most publications. The three most contributed institutions are Astellas Pharma Inc., the Showa University and Glaxosmithkline. Therapeutic Apheresis and Dialysis, American Journal of Nephrology and Clinical Pharmacology in Drug Development are the most productive journals. The main hot topics of HIF-PHI field are anemia, chronic kidney disease, hif-phi, epoetin and roxadustat. Conclusion: The United States and Japan are dominant in the field of HIF-PHI research. The discovery and clinical application of HIF-PHI is a great boon for patients with renal anemia. However, due to the short clinical application time of HIF-PHI, and its long-term efficacy and safety still need time to prove. In addition, more cooperation should be carried out between European and American countries and Asian countries to better prove the clinical value of HIF-PHI.

Amino Acid Profiles and Nutritional Evaluation of Fresh Sweet-Waxy Corn from Three Different Regions of China.

This study conducted a comparative analysis of the amino acid compositions of Chinese Huangnuo 9 fresh sweet-waxy corn from three different provinces in China-Inner Mongolia, Jilin, and Heilongjiang Province. Moreover, we established a nutritive evaluation system based on amino acid profiles to evaluate, compare, and rank the fresh sweet-waxy corn planted in different regions. A total of 17 amino acids were quantified, and the amino acid composition of fresh sweet-waxy corn was analyzed and evaluated. The amino acid quality was determined by the amino acid pattern spectrum, chemical evaluations (including CS, AAS, EAAI, BV, U(a,u), NI, F, predict PER, and PDCAAS), flavor evaluation, amino acid matching degree evaluation, and the results of the factor analysis. The results showed that the protein content of fresh corn 1-1 from Inner Mongolia was the highest (40.26 ± 0.35 mg/g), but the factor analysis results, digestion, and absorption efficiency of fresh corn 1-2 were the best. The amino acid profile of fresh corn 1-1 was closest to each evaluation's model spectrum. The results of the diversity evaluations in fresh corn 3-2 were the best, and fresh corn 3-3 had the most essential amino acid content. A total of 17 amino acids in fresh corn were divided into three principal component factor analyses: functional principal components (Leu, Pro, Glu, His, Ile, Ser, Met, Val, Tyr, Thr), regulatory principal components (Lys, Gly, Ala, Asp, Arg, Trp), and protection principal components (Phe). The scores of the three principal components and the comprehensive score in fresh corn 1-2 were all the highest, followed by 3-3 and 1-1. The amino acid nutritional values of fresh corn 1-2 were the highest in 12 samples.

Fatty Acid Profiles and Nutritional Evaluation of Fresh Sweet-Waxy Corn from Three Regions of China.

Fresh corn is a kind of herbaceous plant with rich nutritive value and a reasonable composition of fatty acids; however, there is little research on methods for the systemic nutritional evaluation of fatty acids in fresh corn. The aim of the present study was to conduct a comparative analysis of the fatty acid profiles of Chinese Huangnuo 9 sweet-waxy corn from the provinces of Inner Mongolia, Jilin, and Heilongjiang by gas chromatography; to establish a nutritional evaluation system according to the impacts of nutrients from fatty acids on human health; and finally, to evaluate, compare and rank fresh sweet-waxy corn grown in different regions. Tocopherols were detected by liquid chromatography in order to demonstrate the anti-oxidation activity of fresh corn's fatty acids. The fatty acid contents and compositions of the 12 samples from the three regions are significantly different from each other. The nutrient value of the fatty acids in fresh corn was analyzed by factor analysis and a linear structural relation model, followed by the fitting and appraising of the model. The studied fresh sweet-waxy corn 1-4 from Inner Mongolia had the highest γ-tocopherol content and the closest saturated fatty acid:monounsaturated fatty acid:polyunsaturated fatty acid rate to the recommended value. The fatty acid profiles of sweet-waxy corns 2-1, 2-2, and 2-3 were the most diverse, and the comprehensive evaluation result of fresh corn 2-4 was the best; its total fatty acid content was the highest. Fresh corn 3-1 in Heilongjiang had the highest unsaturated fatty acids and lower values in its atherosclerosis index and thrombosis index, which suggested the strongest anti-atherosclerosis and anti-thrombotic ability. This work will give a reference to guide dietary choices and provide data support for dietary recommendations for residents.

Simple surrogate equations to predict controlled attenuation parameter values for screening non-alcoholic fatty liver disease in a Chinese population.

Objective: Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease. The controlled attenuation parameter (CAP) obtained by FibroScan reflects the level of liver steatosis in patients with obesity. Our study aimed to construct a simple equation to predict the CAP, to facilitate the screening and monitoring of patients at high risk for NAFLD. Methods: A total of 272 subjects were randomly divided into derivation and validation cohorts at a ratio of 1:2. The derivation set was used for constructing a multiple linear regression model; the validation set was used to verify the validity of the model. Results: Several variables strongly correlated with the CAP were used to construct the following equation for predicting CAP values:CAP1 = 2.4 × BMI + 10.5 × TG+ 3.6 × NC + 10.3 × CP +31.0, where BMI is body mass index, TG is triglyceride, NC is neck circumference and CP is C-peptide. The CAP1 model had an R 2 of 0.764 and adjusted R 2 of 0.753. It was then simplified to derive CAP2 included only simple anthropometric parameters: CAP2 = 3.5 × BMI + 4.2 × NC + 20.3 (R 2 = 0.696, adjusted R 2 = 0.689). The data were well fitted by both models. In the verification group, the predicted (CAP1 and CAP2) values were compared to the actual CAP values. For the CAP1 equation, R 2 = 0.653, adjusted R 2 = 0.651. For the CAP2 equation, R 2 = 0.625, adjusted R 2 = 0.623. The intra-class correlation coefficient (ICC) values were 0.781 for CAP1 and 0.716 for CAP2 (p < 0.001). The actual CAP and the predicted CAP also showed good agreement in Bland-Altman plot. Conclusion: The equations for predicting the CAP value comprise easily accessible variables, and showed good stability and predictive power. Thus, they can be used as simple surrogate tools for early screening and follow-up of NAFLD in the Chinese population.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Detecting Severity and Predicting Outcome after Traumatic Brain Injury in Rats.

After traumatic brain injury (TBI), early assessment of secondary injury severity is critically important for estimating prognosis and treatment stratification. Currently, secondary injury severity is difficult to estimate. The objective of this study was to investigate the capacity of non-invasive amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) techniques to assess TBI injury in different brain regions and predict long-term neurobehavior outcomes. Fifty-five male and female rats were subjected to a controlled cortical impact with one of three different impactor depths to produce different degrees of TBI. Multi-parameter MRI data were acquired on a 4.7-Tesla scanner at 1 h, 1 day, and 3 days. Immunofluorescence staining was used to detect activated microglia at 3 days, and neurobehavioral tests were performed to assess long-term outcomes after 28 days. The APTw signal in the injury core at 1 day correlated with deficits in sensorimotor function, the sucrose preference test (a test for anhedonia), and spatial memory function on the Barnes maze. The APTw signal in the perilesion ipsilateral cortex gradually increased after TBI, and the value at 3 days correlated with microglia density at 3 days and with spatial memory decline and anhedonia at 28 days. The correlation between APTw and activated microglia was also observed in the ipsilateral thalamus, and its correlation to memory deficit and depression was evident in other ipsilateral sites. These results suggest that APTw imaging can be used for detecting secondary injury and as a potential predictor of long-term outcomes from TBI.

Interleukin-10 deficiency aggravates traumatic brain injury in male but not female mice.

The goal of this study was to determine whether deficiency of anti-inflammatory cytokine interleukin-10 (IL-10) affects traumatic brain injury (TBI) outcomes in a sex-dependent manner. Moderate TBI was induced by controlled cortical impact in 8-10 week-old wild-type and IL-10-deficient mice. In wild-type mice, serum IL-10 was significantly increased after TBI in males but not in females. At 4-5 weeks after TBI, sensorimotor function, cognitive function (Y-maze and novel object recognition tests), anxiety-related behavior (light-dark box and open field test), and depression-like behavior (forced swim test) were assessed. IL-10-deficient male mice had larger lesion volumes than did wild-type mice in the early recovery phase and worse performance on sensorimotor tasks, cognitive tests, and anxiety- and depression-related tests in the late recovery phase, whereas female IL-10-deficient mice had lesion volume equivalent to that of wild-type females and worse performance only on sensorimotor tasks. At 3 days after TBI, the number of GFAP- and Iba1-positive cells were augmented in areas in proximity to the injury (cerebral cortex and hippocampus) and in remote functional regions (striatum and amygdala) of IL-10-deficient male, but not female, mice. Moreover, on day 35, significantly fewer NeuN-positive cells were present in cortex, striatum, and amygdala of IL-10-deficient male mice than in wild-type males. This difference was not evident in females. We conclude that IL-10 deficiency aggravates cognitive and emotional recovery from TBI in association with enhanced gliosis and neuronal loss selectively in males, suggesting that recruitment of this cytokine limits damage in a sex-dependent manner.

Identification of novel indole derivatives as highly potent and efficacious LSD1 inhibitors.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent histone demethylase to catalyze the demethylation of H3K4 and H3K9 and thus is an attractive target for therapeutic cancer. Starting with a high micromolar compound 17i, structure-based optimization of novel indole derivatives is described by a bioelectronic isosteric strategy. Grounded by molecular modeling, medicinal chemistry has efficiently yielded low nanomolar LSD1 inhibitors. One of the compounds, B35, exhibited excellent LSD1 inhibition (IC50 = 0.050 ± 0.005 µM) and anti-proliferation against A549 cells (IC50 = 0.74 ± 0.14 µM). The further PK studies indicated compound B35 possessed favorable metabolic stability, in which the plasma t1/2 of p.o. and i.v. were 6.27 ± 0.72 h and 8.78 ± 1.31 h, respectively. Additionally, inhibitor B35 shows a strong antitumor effect and good safety in vivo. Meanwhile, compound B35 regulated genes are closely associated with transcriptional dislocation in cancer and PI3K/AKT pathway involving IGFBP3. Taken together, B35 could be a potent LSD1 inhibitor for further drug development.

Relationship of Oropharyngeal Colonization Microorganisms to Clinical Outcomes within 100 Days after Allogeneic Hematopoietic Stem Cell Transplantation.

Little is known about oropharyngeal colonization microorganisms in patients during allogeneic hematopoietic stem cell transplantation (allo-HSCT), and updated epidemiologic investigations are advisable. This study aimed to characterize oropharyngeal colonization microorganisms in patients during allo-HSCT and confirm whether they were related to clinical outcomes. This retrospective, matched case-control study included 1267 consecutive patients undergoing allo-HSCT between January 2018 and December 2020 at our institution. Patients with oropharyngeal colonization microorganisms were those with a positive throat swab before or on the day of transplantation without the occurrence of any symptoms of infection. Propensity score matching was used. Characteristics of oropharyngeal colonization microorganisms were evaluated among patients in the transplant medicine wards and compared with clinical outcomes within 100 days in positive and negative colonization groups. A total of 127 patients had oropharyngeal colonization microorganisms before or on the day of transplantation. Using propensity score matching, we matched the 127 patients in the positive colonization group with 508 patients in the negative colonization group at a 1:4 ratio (total of 635 cases). None of the differences in clinical traits between the 2 groups remained significant. Among the 127 patients with oropharyngeal colonization microorganisms, 90 patients suffered from the documented infection subsequently, and the others were asymptomatic. A total of 82 single gram-negative bacteria were identified in 127 isolates. There were no differences between the positive and negative colonization groups in the occurrence of oral mucositis, Epstein-Barr virus, or acute graft-versus-host disease and relapse within 100 days. However, the rate of neutrophil or platelet recovery was significantly lower in the positive colonization group compared with the negative colonization group (hazard ratio [HR], .71; 95% confidence interval [CI], .59 to .84; P < .001; HR .69; 95% CI, .58 to .83; P = .003; separately). The risk of bloodstream infection was higher in the positive colonization group compared with the negative colonization group (HR, 6.09; 95% CI, 3.16 to 11.75; P < .001). The continency rate between the bacteria isolated from the blood samples and oropharyngeal colonization microorganisms among the patients with positive results was 73.3%. Patients in the positive colonization group were more vulnerable to cytomegalovirus infection compared with the negative colonization group (HR, 1.41; 95% CI, 1.00 to 1.99; P = .049). The nonrelapse mortality at day +100 was higher in the positive colonization group (HR, 3.46; 95% CI, 1.69 to 7.08; P < .001). The survival probability within 100 days was significantly lower in the positive colonization group (HR, 3.38; 95% CI, 1.78 to 6.41; P < .001). Our data show that the presence of oropharyngeal colonization microorganisms is related to clinical outcomes, and that oropharyngeal microorganism monitoring may be useful during allo-HSCT.

Genetic diagnosis of common fetal renal abnormalities detected on prenatal ultrasound.

OBJECTIVES: This retrospective study aimed to investigate the correlations between phenotypes of fetal renal abnormalities on prenatal ultrasound and genetic aetiologies detected using chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). METHODS: Fetuses with renal abnormalities were subjected to CMA and were further analysed by WES when CMA-negative. The detection rates for chromosomal abnormalities and monogenic variants among different types of isolated renal abnormalities and those with extrarenal abnormalities (non-isolated cases) were determined and compared. RESULTS: CMA detected chromosomal abnormalities in 78 of 577 fetuses (13.52%). WES detected monogenic variants in 31 of 160 fetuses (19.38%) that had non-diagnostic CMA results. In cases of isolated hyperechogenic kidney, polycystic kidney disease, and multicystic dysplastic kidney, the detection rates of copy number variants (CNVs) by CMA and monogenic variants by WES were not significantly different (p > 0.05). However, monogenic variants were more frequently detected than CNVs when kidney abnormalities were accompanied by reduced amniotic fluid (p < 0.05). Other renal abnormalities identified on prenatal ultrasound had different detection rates. CONCLUSIONS: Our findings contribute to the overall knowledge of genetic variants associated with prenatally identified renal anomalies and may aid in decision making regarding prenatal genetic testing options for affected pregnancies.

A Prediction Equation to Estimate Vascular Endothelial Function in Different Body Mass Index Populations.

Objective: Vascular endothelial dysfunction is considered an early predictor of endothelial injury and the initiating factor of atherosclerosis (AS). Brachial artery flow-mediated dilation (FMD) can detect endothelial injury early and provide important prognostic information beyond traditional cardiovascular (CV) risk factors. This study aimed to find the influencing factors of FMD and develop a simple prediction model in populations with different body mass indices (BMIs). Methods: In total, 420 volunteers with different BMIs were recruited in our study. Subjects were randomly assigned to the derivation and validation cohorts (the ratio of the two was 1:2) with simple random sampling. The former was used for influencing factors searching and model construction of FMD and the latter was used for verification and performance evaluation. Results: The population was divided into two groups, i.e., 140 people in the derivation group and 280 people in the verification group. Analyzing in the training data, we found that females had higher FMD than males (p < 0.05), and FMD decreased with age (p < 0.05). In people with diabetes, hypertension or obesity, FMD was lower than that in normal individuals (p < 0.05). Through correlation analysis and linear regression, we found the main influencing factors of FMD: BMI, age, waist-to-hip radio (WHR), aspartate aminotransferase (AST) and low-density lipoprotein (LDL). And we developed a simple FMD prediction model: FMD = -0.096BMI-0.069age-4.551WHR-0.015AST-0.242LDL+17.938, where R2 = 0.599, and adjusted R2 = 0.583. There was no statistically significant difference between the actual FMD and the predicted FMD in the verification group (p > 0.05). The intra-class correlation coefficient (ICC) was 0.77. In a Bland-Altman plot, the actual FMD and the predicted FMD also showed good agreement. This prediction model had good hints in CV risk stratification (area under curve [AUC]: 0.780, 95 % confidence intervals [95% CI]: 0.708-0.852, p < 0.001), with a sensitivity and specificity of 73.8 and 72.1%, respectively. Conclusions: Males, older, obesity, hypertension, diabetes, smoking, etc. were risk factors for FMD, which was closely related to CV disease (CVD). We developed a simple equation to predict FMD, which showed good agreement between the training and validation groups. And it would greatly simplify clinical work and may help physicians follow up the condition and monitor therapeutic effect. But further validation and modification bears great significance.

Symptom management to alleviate thirst and dry mouth in critically ill patients: A randomised controlled trial.

BACKGROUND: Critically ill patients often experience coexisting symptoms. Thirst, in particular, appears to be an important symptom, having the highest prevalence, intensity, and induction of distress, and is significantly correlated with other symptoms. However, thirst and dry mouth are not usually assessed or treated. OBJECTIVES: The aim of the study was to demonstrate the effectiveness of an intervention bundle to relieve thirst and dry mouth. METHODS: The present study was a randomised controlled trial in which critically ill patients were allocated to an experimental or control group. The intervention bundles, including vitamin C sprays, peppermint water mouthwash, and a lip moisturiser, were provided to the experimental group for 3 days, whereas patients in the control group were exposed to the placebo interventions, including saline sprays, 40 °C water mouthwash, and wetting the lips with water. RESULTS: A total of 61 patients were recruited to the study; 65.6% (n = 41) were men, and the average age was 64.2 ± 16.8 years. The average decrease in thirst intensity and oral mucosa situation scores after the interventions was larger in the experimental group patients relative to controls (1.27 and 0.36 vs. 0.19 and 0.1 points, respectively; p < 0.05). Being male, scoring highly on the Acute Physiology and Chronic Health Evaluation II scale, not receiving diuretics, and having higher serum sodium levels were potential predictors of thirst and oral dryness. CONCLUSIONS: The interventional bundle used in this study was shown to be a promising approach that can relieve thirst intensity and dry mouth, which are pervasively distressful to critically ill patients. CLINICAL TRIAL REGISTRATION NUMBERS: The study was registered on the www.Chictr.org.cn under the identification number ChiCTR1900022873.

Changes in muscle ultrasound for the diagnosis of intensive care unit acquired weakness in critically ill patients.

To test diagnostic accuracy of changes in thickness (TH) and cross-sectional area (CSA) of muscle ultrasound for diagnosis of intensive care unit acquired weakness (ICU-AW). Fully conscious patients were subjected to muscle ultrasonography including measuring the changes in TH and CSA of biceps brachii (BB) muscle, vastus intermedius (VI) muscle, and rectus femoris (RF) muscles over time. 37 patients underwent muscle ultrasonography on admission day, day 4, day 7, and day 10 after ICU admission, Among them, 24 were found to have ICW-AW. Changes in muscle TH and CSA of RF muscle on the right side showed remarkably higher ROC-AUC and the range was from 0.734 to 0.888. Changes in the TH of VI muscle had fair ROC-AUC values which were 0.785 on the left side and 0.779 on the right side on the 10th day after ICU admission. Additionally, Sequential Organ Failure Assessment (SOFA), Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores also showed good discriminative power on the day of admission (ROC-AUC 0.886 and 0.767, respectively). Ultrasonography of changes in muscles, especially in the TH of VI muscle on both sides and CSA of RF muscle on the right side, presented good diagnostic accuracy. However, SOFA and APACHE II scores are better options for early ICU-AW prediction due to their simplicity and time efficiency.

Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. In particular, the representative compound 17i exhibited excellent LSD1 inhibition at the molecular levels with IC50 = 0.065 µM, as well as anti-proliferation against MCF-7, MGC-803, H460, A549 and THP-1 tumor cells with IC50 values of 2.90 ± 0.32, 5.85 ± 0.35, 2.06 ± 0.27, 5.74 ± 1.03 and 6.15 ± 0.49 µM, respectively. The binding modes of these compounds were rationalized by molecular docking. Meanwhile, a preliminary druggability evaluation showed that compound 17i displayed favorable liver microsomal stability and weak inhibitory activity against CYPs at 10 µM. Remarkably, H460 xenograft tumors studies revealed that 17i demonstrated robust in vivo antitumor efficacy without significant side effects. All the results demonstrated that compound 17i could represent a promising lead for further development.