Ratio of waist circumference to body mass index: A novel predictor of clinical outcome in hypertension patients.

We aim to investigate the influence of waist circumference and body mass index (BMI) on all-cause death and cardiovascular-specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all-cause mortality and cardiovascular events. The waist circumference-to-BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan-Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all-cause mortality. Subsequently, Fine-Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular-specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P < .05), while no significant difference was observed in waist circumference (P = .373). When analyzed as continuous, the risk of all-cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06-2.85). The restricted cubic spline illustrated an elevated risk of all-cause mortality as WtBR increased (J-shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular-specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all-cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity-related health.

Protective mechanisms of quercetin in neonatal rat brain injury induced by hypoxic-ischemic brain damage (HIBD).

Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality worldwide. This study explored whether quercetin (Que) exerts neuroprotective effects in a rat model of HIBD. A total of 36 seven-day-old Sprague-Dawley rats were divided into control, Que, HI, and HI + Que groups. The Rice method was used to establish HIBD in HI and HI + Que rats, which were treated with hypoxia (oxygen concentration of 8%) for 2 h after ligation of the left common carotid artery. The rats in the HI + Que group were intraperitoneally injected with Que (30 mg/kg) 1 h before hypoxia, and the rats in the Que group were only injected with the same amount of Que. Brain tissues were harvested 24 h postoperation and assessed by hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay; relative gene and protein levels were evaluated by RT-qPCR, IHC, or western blot (WB) assay. Brain tissue morphologies were characterized by transmission electron microscopy (TEM); LC3B protein levels were assessed by immunofluorescence staining. Escape latencies and platform crossing times were significantly improved (p < .05) in HI + Que groups; infarct volume significantly decreased (p < .001), whereas the numbers of autophagic bodies and apoptotic cells increased and decreased, respectively. Meanwhile, NLRX1, ATG7, and Beclin1 expressions were significantly upregulated, and mTOR and TIM23 expressions, LC3B protein level, and LC 3II/LC 3I ratio were significantly downregulated. Que exerted neuroprotective effects in a rat model of HIBD by regulating NLRX1 and autophagy.

Obesity, malnutrition, and the prevalence and outcome of hypertension: Evidence from the National Health and Nutrition Examination Survey.

Background: Nutritionally unhealthy obesity is a newly introduced phenotype characterized by a combined condition of malnutrition and obesity. This study aims to explore the combined influence of obesity and nutritional status on the prevalence and outcome of hypertension. Methods: Participants collected from the National Health and Nutrition Examination Survey (NHANES) database were divided into four subgroups according to their obesity and nutritional conditions, as defined by waist circumference and serum albumin concentration. The lean-well-nourished was set as the reference group. Logistic regression models were applied to evaluate the hypertension risk. Kaplan-Meier analysis and Cox proportional hazard regression models were used to assess the survival curve and outcome risk of participants with hypertension. Results: A total of 28,554 participants with 10,625 hypertension patients were included in the analysis. The lean-malnourished group showed a lower hypertension risk (odds ratio [OR] 0.85, 95% confidence interval [CI]: 0.77-0.94), while the obese-well-nourished condition elevated the risk (OR 1.47, 95% CI: 1.3-1.67). Two malnourished groups had higher mortality risks (HR 1.42, 95% CI: 1.12-1.80 and HR 1.31, 95% CI: 1.03-1.69 for the lean and obese, respectively) than the reference group. The outcome risk of the obese-well-nourished group (HR 1.02, 95% CI: 0.76-1.36) was similar to the lean-well-nourished. Conclusion: Malnutrition was associated with a lower risk of developing hypertension in both lean and obese participants, but it was associated with a worse outcome once the hypertension is present. The lean-malnourished hypertension patients had the highest all-cause mortality risk followed by the obese-malnourished. The obese-well-nourished hypertension patients showed a similar mortality risk to the lean-well-nourished hypertension patients.

Noninvasive Mechanical Ventilation in Patients with Viral Pneumonia-Associated Acute Respiratory Distress Syndrome: An Observational Retrospective Study.

Objectives: Appropriate mechanical ventilation may change the prognosis of patients with viral pneumonia-associated acute respiratory distress syndrome (ARDS). This study aimed to identify the factors associated with the success of noninvasive ventilation in the management of patients with ARDS secondary to respiratory viral infection. Methods: In this retrospective cohort study, all patients with viral pneumonia-associated ARDS were divided into the noninvasive mechanical ventilation (NIV) success group and the NIV failure group. The demographic and clinical data of all patients were collected. The factors associated with the success of noninvasive ventilation were identified by the logistic regression analysis. Results: Among this cohort, 24 patients with an average age of 57.9 ± 17.0 years received successful NIVs, and NIV failure occurred in 21 patients with an average age of 54.1 ± 14.0 years. The independent influencing factors for the success of the NIV were the acute physiology and chronic health evaluation (APACHE) II score (odds ratio (OR): 1.83, 95% confidence interval (CI): 1.10-3.03) and lactate dehydrogenase (LDH) (OR: 1.011, 95% CI: 1.00-1.02). When the oxygenation index (OI) is <95 mmHg, APACHE II > 19, and LDH > 498 U/L, the sensitivity and specificity of predicting a failed NIV were (66.6% (95% CI: 43.0%-85.4%) and 87.5% (95% CI: 67.6%-97.3%)); (85.7% (95% CI: 63.7%-97.0%) and 79.1% (95% CI: 57.8%-92.9%)); (90.4% (95% CI: 69.6%-98.8%) and 62.5% (95% CI: 40.6%-81.2%)), respectively. The areas under the receiver operating characteristic curve (AUC) of the OI, APACHE II scores, and LDH were 0.85, which was lower than the AUC of the OI combined with LDH and the APACHE II score (OLA) of 0.97 (P=0.0247). Conclusions: Overall, patients with viral pneumonia-associated ARDS receiving successful NIV have lower mortality rates than those for whom NIV failed. In patients with influenza A-associated ARDS, the OI may not be the only indicator of whether NIV can be used; a new indicator of NIV success may be the OLA.

Base-Promoted Decarboxylative Annulation of Methyl 2-(2-Bromophenyl)acetates and Ynones to Access Benzoxepines.

A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates has been developed. A broad range of benzoxepines were prepared with a broad substrate scope and high regioselectivity in moderate to excellent yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and the intramolecular nucleophilic aromatic substitution reaction. Additionally, the key intermediates were successfully obtained and characterized unambiguously by single-crystal X-ray crystallography, which could favorably support a decarboxylative annulation mechanism. Furthermore, gram-scale reaction and synthetic applications for the further functionalization are also studied.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Effect of intradermal needle therapy at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors.

BACKGROUND: Postoperative gastrointestinal function recovery is critical for rapid rehabilitation of patients with gastrointestinal tumors. Traditional Chinese medicine offers considerable advantages for gastrointestinal disease treatment. However, no study has reported the clinical efficacy of intradermal needle therapy (INT) at the Yuan-source, Luo-connecting, and He-sea points of the corresponding meridian for gastrointestinal function in patients following surgery for gastrointestinal tumors. AIM: To investigate the effect of INT at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors. METHODS: This randomized controlled trial was conducted at the Second Affiliated Hospital of Xi'an Jiaotong University on patients with diagnosed gastrointestinal cancer, no distant metastases or organ failure, and hospitalized for elective radical tumor resection, who did not receive preoperative radiotherapy or chemotherapy. Participants were randomly allocated to either the intervention (n = 32) or the control (n = 32) group. Participants in the control group received enhanced recovery care, while those in the intervention group received enhanced recovery care combined with INT at the Yuan-source, Luo-connecting, and He-sea points. After surgery, INT was performed immediately upon the patient's return to the ward, and continued for seven consecutive days. The independent samples t-test, chi-square test, and generalized estimating equations were used for data analysis. RESULTS: The participants' ages ranged from 40 to 80 years (average 63 ± 10.1 years). Most participants underwent surgery for either gastric (43.8%) or colon cancer (39.1%) and had adenocarcinoma (87.5%). Significant differences were noted in time to first postoperative flatus passage (66 ± 27 h vs 103 ± 41 h, P < 0.001), time to first defecation (106 ± 44 h vs 153 ± 50 h, P < 0.001), and time to first oral feeding (73 ± 30 h vs 115 ± 38 h, P < 0.001) between the intervention and control groups. Gastrointestinal symptoms, including abdominal distension, nausea, and fatigue 48 h and 72 h after surgery, were significantly alleviated in the intervention group compared with that observed in the control group (P < 0.05). CONCLUSION: INT at the Yuan-source, Luo-connecting, and He-sea points can promote recovery of gastrointestinal function and ease gastrointestinal symptoms in patients following surgical resection of gastrointestinal tumors.

TDP-43 upregulates lipid metabolism modulator ABHD2 to suppress apoptosis in hepatocellular carcinoma.

TAR DNA-Binding Protein 43 (TDP-43) has been well studied in neurodegenerative diseases, but its potential role in malignance is still unclear. Here, we demonstrate that TDP-43 contributes to the suppression of apoptosis by facilitating lipid metabolism in hepatocellular carcinoma (HCC). In HCC cells, TDP-43 is able to suppress apoptosis while deletion of it markedly induces apoptosis. RNA-sequencing identifies the lipid metabolism gene abhydrolase domain containing 2 (ABHD2) as the target gene of TDP-43. Tissue microarray analysis shows the positive correlation of TDP-43 and ABHD2 in HCC. Mechanistically, TDP-43 binds with the UG-rich sequence1 of ABHD2 3'UTR to enhance the mRNA stability of ABHD2, thereby upregulating ABHD2. Afterwards, TDP-43 promotes the production of free fatty acid and fatty acid oxidation-originated reactive oxygen species (ROS) in an ABHD2-dependent manner, so as to suppress apoptosis of HCC. Our findings provide insights into the mechanism of HCC progression and reveal TDP-43/ABHD2 as potential targets for the precise treatment of HCC.

Alcohol Consumption and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis of Prospective Studies.

Background: This study aimed to investigate the dose-response association between alcohol consumption and atrial fibrillation (AF) risk. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using keywords related to alcohol and AF from the establishment of databases up to 1 March 2021. Prospective studies examining the impact of alcohol on the risk of AF with hazard ratios (HRs) were included. Restricted cubic spline regression was performed to quantify the dose-response relationship between alcohol consumption and AF risk. Results: Thirteen eligible studies were included in the meta-analysis, with a total of 645,826 participants and 23,079 cases of AF. When compared with non-/seldom-drinkers, the pooled adjusted HRs of AF were 1.30 (95% confidence interval [CI]: 1.20-1.41) and 1.00 (95% CI: 0.96-1.05) for high and low alcohol consumption, respectively. Moderate alcohol intake significantly increased the risk of AF in males (HR, 1.21; 95% CI: 1.10-1.33) but not in females (HR, 1.02; 95% CI: 0.91-1.14). The cubic spline regression analysis illustrated that the risk of AF significantly increased with daily alcohol intake in a Non-linear manner (R2 = 0.64, P = 5.785 × 10-12). Conclusion: This study revealed a Non-linearly positive association between alcohol intake and the risk of AF. Low alcohol intake was not associated with the development of AF, whereas moderate alcohol intake significantly increased the risk of AF in males but not in females. Our meta-analysis highlighted that alcohol consumption should be restricted to a low level to reduce the risk of AF.

Comparison of Conduits Fabricated by Fresh and Predegenerated Skeletal Muscles for Peripheral Nerve Repairing.

ABSTRACT: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect.

Spatiotemporal Quantification of Endosomal Acidification on the Viral Journey.

Many enveloped viruses utilize endocytic pathways and vesicle trafficking to infect host cells, where the acidification of virus-containing endosomes triggers the virus-endosome fusion events. Therefore, simultaneous correlation of intracellular location, local pH, and individual virus dynamics is important for gaining insight into viral infection mechanisms. Here, an imaging approach is developed for spatiotemporal quantification of endosomal acidification on the viral journey in host cells using a fluorescence resonance energy transfer based ratiometric pH sensor consisting of a photostable and high-brightness QD, pH-sensitive fluorescent dyes, and virus-binding proteins. Ratiometric analysis of sensor-based single-virus tracking data enables to dissect a two-step endosomal acidification process during the infection of influenza viruses and elucidates the occurrence of the fission and sorting of virus-containing endosomes to recycling endosomes after initial acidification. This technique should serve as a robust approach for in situ quantification of endosomal acidification on the viral journey.

Near-Infrared-II Quantum Dots for In Vivo Imaging and Cancer Therapy.

In vivo fluorescence imaging can perform real-time, noninvasive, and high spatiotemporal resolution imaging to accurately obtain the dynamic biological information in vivo, which plays significant roles in the early diagnosis and treatment of cancer. However, traditional in vivo fluorescence imaging usually operates in the visible and near-infrared (NIR)-I windows, which are severely interfered by the strong tissue absorption, tissue scattering, and autofluorescence. The emergence of NIR-II imaging at 1000-1700 nm significantly breaks through the imaging limitations in deep tissues, due to less tissue scattering and absorption. Benefiting from the outstanding optical properties of NIR-II quantum dots (QDs), such as high brightness and good photostability, in vivo fluorescence imaging exhibits excellent temporal-spatial resolution and large penetration depth, and QDs have become a kind of promising fluorescent biomarkers in the field of in vivo fluorescence imaging. Herein, the authors review NIR-II QDs from preparation to modification, and summarize recent applications of NIR-II QDs, including in vivo imaging and imaging-guided therapies. Finally, they discuss the special concerns when NIR-II QDs are shifted from in vivo imaging applications to further in-depth applications.

Predictive modeling the probability of suffering from metabolic syndrome using machine learning: A population-based study.

Background: There is an increasing trend of Metabolic syndrome (MetS) prevalence, which has been considered as an important contributor for cardiovascular disease (CVD), cancers and diabetes. However, there is often a long asymptomatic phase of MetS, resulting in not diagnosed and intervened so timely as needed. It would be very helpful to explore tools to predict the probability of suffering from MetS in daily life or routinely clinical practice. Objective: To develop models that predict individuals' probability of suffering from MetS timely with high efficacy in general population. Methods: The present study enrolled 8964 individuals aged 40-75 years without severe diseases, which was a part of the REACTION study from October 2011 to February 2012. We developed three prediction models for different scenarios in hospital (Model 1, 2) or at home (Model 3) based on LightGBM (LGBM) technique and corresponding logistic regression (LR) models were also constructed for comparison. Model 1 included variables of laboratory tests, lifestyles and anthropometric measurements while model 2 was built with components of MetS excluded based on model 1, and model 3 was constructed with blood biochemical indexes removed based on model 2. Additionally, we also investigated the strength of association between the predictive factors and MetS, as well as that between the predictors and each component of MetS. Results: In this study, 2714 (30.3%) participants suffer from MetS accordingly. The performances of the LGBM models in predicting the probability of suffering from MetS produced good results and were presented as follows: model 1 had an area under the curve (AUC) value of 0.993 while model 2 indicated an AUC value of 0.885. Model 3 had an AUC value of 0.859, which is close to that of model 2. The AUC values of LR model 1 and 2 for the scenario in hospital and model 3 at home were 0.938, 0.839 and 0.820 respectively, which seemed lower than that of their corresponding machine learning models, respectively. In both LGBM and logistic models, gender, height and resting pulse rate (RPR) were predictors for MetS. Women had higher risk of MetS than men (OR 8.84, CI: 6.70-11.66), and each 1-cm increase in height indicated 3.8% higher risk of suffering from MetS in people over 58 years, whereas each 1- Beat Per Minute (bpm) increase in RPR showed 1.0% higher risk in individuals younger than 62 years. Conclusion: The present study showed that the prediction models developed by machine learning demonstrated effective in evaluating the probability of suffering from MetS, and presented prominent predicting efficacies and accuracies. Additionally, we found that women showed a higher risk of MetS than men, and height in individuals over 58 years was important factor in predicting the probability of suffering from MetS while RPR was of vital importance in people aged 40-62 years.

Sublethal Exposure to Deltamethrin Stimulates Reproduction and Alters Symbiotic Bacteria in Aphis gossypii.

In aphids, hormesis and symbiotic bacteria are the drivers for the development of pesticide resistance. However, the related mechanism remains unclear. Here, we evaluated the sublethal and transgenerational effects of the extensively used pyrethroid pesticide deltamethrin (DMT) on the population dynamics in Aphis gossypii and tested its influence on symbiotic bacterial communities. The leaf-dip bioassay revealed that DMT was highly toxic to A. gossypii, and at a low lethal concentration of DMT, the intrinsic (r) and finite rates of increase (λ) of the initially exposed aphids (G0) significantly decreased. Intriguingly, the r, λ, and net reproductive rate (R0) of G1 and G2 significantly increased, but the r and λ decreased in G3. The adult and total preoviposition period increased in G3 but decreased in G4. Additionally, the diversity of the bacterial community decreased, while the abundance values of Buchnera, Pseudomonadaceae, and Burkholderiaceae increased after 24 h of exposure to LC30 DMT in G0 aphids, and the latter two decreased in G1 but increased in G2. In summary, sublethal DMT has intergenerational hormesis effect on cotton aphids in G1-G2 and remarkably altered their symbiotic bacterial community and abundance. These results broaden our understanding of the relationship of hormesis and symbiotic bacteria in aphids under insecticide exposure.

Integrative Analyses of Genes Associated with Hashimoto's Thyroiditis.

OBJECTIVE: Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is a common autoimmune thyroiditis, which mostly occurs in young and middle-aged women. It can be manifested as hyperthyroidism in the early stage; hypothyroidism may appear with the progression of the disease. Studies have shown that multiple factors such as heredity, environment, and autoimmunity are involved in the pathogenesis, but the specific mechanism is not clear. In our study, we tried to find key genes and potential molecular mechanisms of Hashimoto's thyroiditis to provide new ideas for the therapeutic targets of Hashimoto's thyroiditis. METHOD: GSE138198 and GSE54958 were downloaded from the GEO database, and two datasets were combined for analysis. The combined data were normalized to identify the differentially expressed genes (DEGs), and GO and KEGG enrichment analyses were performed. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. We also used the miRWalk database to identify regulatory miRNAs associated with expressions of DEGs. RESULT: We identified 182 DEGs (160 upregulated and 22 downregulated) between Hashimoto's disease patients and the healthy control group. GO analysis showed that DEGs were mostly concentrated in detection of chemical stimulus involved in sensory perception, intermediate filament cytoskeleton, and olfactory receptor activity. KEGG pathway analysis showed that DEGs were mainly related to olfactory transduction. Some members of the KRTAP family and HTR5A, KNG1, DRD3, HTR1D, TAS2R16, INSL5, TAS2R42, and GRM7 are the most important hub genes in the PPI network. In addition, we recognized that OTUD4, LLPH, and ECHDC1 were the most important hub genes in the miRNA-target gene network. CONCLUSION: In this study, a series of bioinformatics analyses of DEGs were performed to identify the key genes and pathways associated with Hashimoto's thyroiditis. These genes and pathways provide a more detailed understanding of the pathogenesis of Hashimoto's disease and provide new ideas for the therapeutic targets of Hashimoto's thyroiditis.

Hypothalamic Perineuronal Nets Are Regulated by Sex and Dietary Interventions.

Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets.

MXRA5 Is a Novel Immune-Related Biomarker That Predicts Poor Prognosis in Glioma.

BACKGROUND: Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value. METHODS: In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples. RESULTS: We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. CONCLUSION: Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation.

The atmospheric lead emission, deposition, and environmental inequality driven by interprovincial trade in China.

Lead (Pb) as a hazardous air pollutant has raised widespread concerns due to its adverse and toxic effects on the ecological environment and human health. Here we integrated the multi-regional input-output (MRIO) model and an atmospheric transport model to examine regional environmental inequality (REI) index induced by Pb emission transfers, and to evaluate the impacts of interprovincial trade on regional atmospheric Pb concentrations and dry deposition fluxes in China in 2012. In 2012, approximately 57.4% ~ 72.6% of Pb emissions in well-developed eastern regions (Beijing-Tianjin, Yangtze River Delta (YRD)) and the southern seaboard of China were embodied in other regions in China subject to the demands from these well-developed regions to industrial products and services. Our results, based on the net virtual flows of Pb emission and value-added, indicate that most provinces in the eastern seaboard of China outsource Pb emission and benefit from the interprovincial trade by reducing their Pb emissions. REI indexes show that the well-developed Guangdong province outsources its Pb emission but has low economic gains. Many less-developed provinces in central China enhance virtual Pb emission inflow but have high economic gains. Whereas, inland provinces in western China not only experience Pb emission increase, but also suffer from indirect economic loss due to trade with well-developed provinces to meet their increasing demands to Pb emission abundant industrial products from these provinces in eastern China which are mostly provided by less-developed but energy and mineral product abundant provinces in western China. For example, the province pair with highest REI index was Jiangsu-Inner Mongolia (REI = 2.47), which revealed that Jiangsu was the largest beneficiary which exported 37.2 t of net Pb emission and gained value-added of 521.4 billion RMB through trade with Inner Mongolia which suffered from both virtual Pb inflow and economic loss in 2012. As a result of interprovincial trade, Pb dry deposition in central and eastern China was decreased but increased in western China. Overall, interprovincial trade reduced 17.6% of atmospheric Pb dry deposition in China.

Recombinant human adenovirus type 5 (Oncorine) reverses resistance to immune checkpoint inhibitor in a patient with recurrent non-small cell lung cancer: A case report.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various solid tumors, but only a small subgroup of patients benefit from them because of immune resistance. Oncorine (formerly H101), a recombinant human adenovirus type 5, has direct anticancer properties and enhances cell-mediated immune responses. At present, few studies on the role of Oncorine in reversing resistance to ICIs have been reported. Here, we present a case with recurrent non-small cell lung cancer (NSCLC). The patient developed resistance to nivolumab therapy. After trying immunotherapy plus chemotherapy or antiangiogenesis therapy, the patient only obtained a transient response. The patient then received experimental treatment with Oncorine together with nivolumab and anlotinib. She experienced symptomatic improvement with a performance status score of 1, and achieved stable disease despite partial lung tissue necrosis. This was a successful exploration of oncolytic viruses reversing immune resistance.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.