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.

SARS-CoV-2 E protein-induced THP-1 pyroptosis is reversed by Ruscogenin.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging pathogenic coronavirus, has been reported to cause excessive inflammation and dysfunction in multiple cells and organs, but the underlying mechanisms remain largely unknown. Here we showed exogenous addition of SARS-CoV-2 envelop protein (E protein) potently induced cell death in cultured cell lines, including THP-1 monocytic leukemia cells, endothelial cells and bronchial epithelial cells, in a time- and concentration-dependent manner. SARS-CoV-2 E protein caused pyroptosis-like cell death in THP-1 and led to GSDMD cleavage. In addition, SARS-CoV-2 E protein up-regulated the expression of multiple pro-inflammatory cytokines that may be attributed to activation of NF-κB, JNK and p38 signal pathways. Notably, we identified a natural compound, Ruscogenin, effectively reversed E protein-induced THP-1 death via inhibition of NLRP3 activation and GSDMD cleavage. In conclusion, these findings suggested that Ruscogenin may have beneficial effects on preventing SARS-CoV-2 E protein-induced cell death and might be a promising treatment for the complications of COVID-19.

Prevalence of unpaid caregiving, pain, and depression in older seriously ill patients undergoing elective surgery.

INTRODUCTION: Serious illness is a life-limiting condition negatively impacting daily function, quality of life, or excessively straining caregivers. Over 1 million older seriously ill adults undergo major surgery annually, and national guidelines recommend that palliative care be available to all seriously ill patients. However, the palliative care needs of elective surgical patients are incompletely described. Understanding baseline caregiving needs and symptom burden among seriously ill older surgical patients could inform interventions to improve outcomes. METHODS: Using Health and Retirement Study data (2008-2018) linked to Medicare claims, we identified patients ≥66 years who met an established serious illness definition from administrative data and underwent major elective surgery using Agency for Healthcare Research and Quality (AHRQ) criteria. Descriptive analyses were performed for preoperative patient characteristics, including: unpaid caregiving (no or yes); pain (none/mild or moderate/severe); and depression (no, CES-D < 3, or yes, CES-D ≥ 3). Multivariable regression was performed to examine the association between unpaid caregiving, pain, depression, and in-hospital outcomes, including hospital days (days admitted between discharge date and one-year post-discharge), in-hospital complications (no or yes), and discharge destination (home or non-home). RESULTS: Of the 1343 patients, 55.0% were female and 81.6% were non-Hispanic White. Mean age was 78.0 (SD 6.8); 86.9% had ≥2 comorbidities. Before admission, 27.3% of patients received unpaid caregiving. Pre-admission pain and depression were 42.6% and 32.8%, respectively. Baseline depression was significantly associated with non-home discharge (OR 1.6, 95% CI 1.2-2.1, p = 0.003), while baseline pain and unpaid caregiving needs were not associated with in-hospital or post-acute outcomes in multivariable analysis. CONCLUSIONS: Prior to elective surgery, older adults with serious illnesses have high unpaid caregiving needs and a prevalence of pain and depression. Baseline depression alone was associated with discharge destinations. These findings highlight opportunities for targeted palliative care interventions throughout the surgical encounter.

Nicaraven protects against endotoxemia-induced inflammation and organ injury through modulation of AMPK/Sirt1 signaling in macrophages.

Endotoxemia is a disease characterized by systemic inflammatory responses and organ injury caused by lipopolysaccharide (LPS) infection, with high mortality. Nicaraven (AVS), a potent hydroxyl radical scavenger, has been proven to regulate the inflammatory response in tumors. To investigate the protective effects and mechanisms of AVS in endotoxemia, mice were injected intraperitoneally with LPS to induce endotoxemia. AVS treatment significantly decreased the levels of pro-inflammatory cytokines in the serum, reduced neutrophil infiltration, attenuated multiple organ injury, and increased the survival rate in LPS-challenged mice. In the LPS-induced inflammatory model of macrophages, AVS inhibited macrophage activation, suppressed nitric oxide (NO) production, and inhibited the expression and secretion of pro-inflammatory cytokines. Mechanistically, AVS treatment up-regulated silence information regulator transcript-1 (Sirt1) expression in a time- and dose-dependent manner. AVS treatment activated the AMP-dependent protein kinase (AMPK)/Sirt1 signaling pathway and suppressed the activation of nuclear factor kappa B (NF-κB) in macrophages exposed to LPS. However, the anti-inflammatory effects of AVS could be reversed by the AMPK, the Sirt1 inhibitor, or the histone deacetylase inhibitor. We confirmed that the AMPK inhibitor inhibited AVS-mediated AMPK/Sirt1 activation and NF-κB p65 acetylation. These results suggested that AVS alleviated endotoxemia by activating the AMPK/Sirt1 signaling pathway in macrophages.

Application of machine learning in prediction of bone cement leakage during single-level thoracolumbar percutaneous vertebroplasty.

BACKGROUND: In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. METHODS: The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. RESULTS: The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. CONCLUSION: In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.

[Randomized Controlled Study on the Improvement of Community Residents' Mental Health Literacy Through Online Popular Science Program].

Objective: To explore the effects of online mental health promotion intervention consisting of popular science articles and short videos on the level of mental health literacy (MHL), the MHL competency rate, and depression and anxiety levels of local residents. Methods: Local residents in Shanghai were recruited for the study and assigned to a control group ( n=53) and a study group ( n=53) with a random number table. The study group participated in a 12-session mental health promotion intervention program that was carried out over the course of 4 weeks, while the control group did not receive any intervention. The subjects were assessed for their MHL, depression and anxiety by questionnaire surveys at the baseline (T1), after intervention (T2), and three months after intervention (T3). Results: At T2, there was significant difference in the rate of MHL competency between the study group (43.40%) and the control group (18.87%) ( P=0.006). There was no significant difference between the two groups at T1 ( P=0.787) or T3 ( P=0.840). The results of repeated measures analysis of variance of the total score of the MHL Questionnaire showed that the interaction effect was statistically significant ( F=9.708, P<0.001), the simple effect of grouping was statistically significant at T2 ( F=10.935, P=0.001), and the total score of MHL of the study group (134.321±20.123) was significantly higher than that of the control group (123.811±20.224) for the corresponding point of time. The simple effect of time in the study group was statistically significant ( F=23.233, P<0.001). The subjects in the study group scored significantly higher at T2 and T3 than they did at T1, or the baseline ( P<0.001). There was no significant difference between the T2 and the T3 scores ( P=0.847). Conclusion: The 12-session online mental health promotion intervention can effectively improve the subjects' MHL level and the rate of MHL competency immediately after the invention was completed, and the effect endures 3 months after intervention.

Comparative efficacy of hypnotics in young and middle-aged adults with insomnia: a systematic review and network meta-analysis.

OBJECTIVE/BACKGROUND: Insomnia is highly prevalent in modern society. However, the hierarchical selection of hypnotics in young and middle-aged adults with insomnia remains unclear. We aimed to compare the efficacy and daytime drowsiness associated with different hypnotics for treating insomnia in young and middle-aged adults. METHODS: We searched Embase, PubMed, Cochrane Library, and ProQuest Dissertations and Theses A&I databases from inception until December 15, 2021. We also manually searched reference lists and relevant publications. The literature search, data collection, and risk of bias evaluation were all carried out separately by pairs of reviewers. We included randomized control trials (RCTs) that compared hypnotics approved by the Food and Drug Administration. The R and Stata software were both used to perform the meta-analysis. RESULTS: In total, 117 RCTs comprising 22,508 participants with the age of 18 to 65 years were included. Assessment of the efficacy of the hypnotics and adverse events (drowsiness) revealed that zolpidem improved all objective sleep parameters (oTST, oSOL, oWASO, and oSE), zopiclone increased oTST and oSE and reduced oSOL, and daridorexant increased oTST and reduced oWASO. Regarding subjective sleep outcomes, zolpidem exhibited beneficial effects on sTST, sSOL, and sWASO. Zaleplon reduced sSOL, and zopiclone was the recommended hypnotic for improving SQ. Zolpidem was associated with drowsiness effect (odds ratio = 1.82; 95% confidence interval = 1.25 to 2.65). The results of sensitivity analysis remained unchanged after the exclusion of studies reporting long-term effects. CONCLUSION: Zolpidem is recommended for managing sleep-onset insomnia and sleep maintenance insomnia but should be used with caution because of daytime drowsiness effects. Daridorexant is recommended as a promising agent for managing sleep maintenance insomnia.

Effects of Arbuscular Mycorrhizal Fungus on Sodium and Chloride Ion Channels of Casuarina glauca under Salt Stress.

Casuarina glauca is an important coastal protection forest species, which is exposed to high salt stress all year round. Arbuscular mycorrhizal fungi (AMF) can promote the growth and salt tolerance of C. glauca under salt stress. However, the effects of AMF on the distribution of Na+ and Cl- and the expression of related genes in C. glauca under salt stress need to be further explored. This study explored the effects of Rhizophagus irregularis on plant biomass, the distribution of Na+ and Cl-, and the expression of related genes in C. glauca under NaCl stress through pot simulation experiments. The results revealed that the mechanisms of Na+ and Cl- transport of C. glauca under NaCl stress were different. C. glauca took a salt accumulation approach to Na+, transferring Na+ from roots to shoots. Salt accumulation of Na+ promoted by AMF was associated with CgNHX7. The transport mechanism of C. glauca to Cl- might involve salt exclusion rather than salt accumulation, and Cl- was no longer transferred to shoots in large quantities but started to accumulate in roots. However, AMF alleviated Na+ and Cl- stress by similar mechanisms. AMF could promote salt dilution of C. glauca by increasing biomass and the content of K+, compartmentalizing Na+ and Cl- in vacuoles. These processes were associated with the expression of CgNHX1, CgNHX2-1, CgCLCD, CgCLCF, and CgCLCG. Our study will provide a theoretical basis for the application of AMF to improve salt tolerance in plants.

Transcription-wide impact by RESCUE-induced off-target single nucleotide variants in mammalian cell.

RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIR and RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUE can generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced off-target single nucleotide variants is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediated editing, we employed transcription-wide sequencing on cells edited by RESCUE. The single nucleotide variants showed different off-target effects on mRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcription-wide impact of RESCUE induced off-target single nucleotide variants and highlight the need for careful characterization of the off-target impact by this editing platform.

Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

Purpose: Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel. Methods: We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel. Results: The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT. Conclusion: Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.

The burden of pre-admission pain, depression, and caregiving on palliative care needs for seriously ill trauma patients.

INTRODUCTION: Increasing numbers of individuals admitted to hospitals for trauma are older adults, many of whom also have underlying serious illnesses. Older adults with serious illness benefit from palliative care, but the palliative care needs of seriously ill older adults with trauma have not been elucidated. We hypothesize that older adults with serious illness have a high prevalence of pain, depression, and unpaid caregiving hours before trauma admission. METHODS: Using Health and Retirement Study data (2008-2018) linked to Medicare claims, we identified patients 66 years or older who met an established definition of serious illness in surgery and were admitted with trauma. Descriptive analyses were performed for baseline patient characteristics, pre-admission pain (dichotomized as none/mild vs. moderate/severe), depression (dichotomized as no, Center for Epidemiologic Studies Depression scale [CES-D] < 3 vs. yes, CES-D ≥ 3), and unpaid caregiving hours (dichotomized as low (<30 h/month), high (≥30 h/month)). RESULTS: We identified 1741 patients, 67.4% were female and 86.8% White. Mean age was 83 (SD 7.5), and 60.3% had ≥4 comorbidities. The majority (62.9%) were admitted due to falls, 33.5% had isolated hip fracture. The prevalence of baseline moderate/severe pain and depression were 38.1% and 42.6%, respectively. Among the cohort, 42.2% had unpaid caregiving, of those 27.7% had ≥30 h/week of unpaid caregiving hours. CONCLUSIONS: Prior to trauma admission, older adults with serious illness have a high prevalence of pain, depression, and unpaid caregiving hours. These findings may inform targeted palliative care interventions to reduce symptom burden and post-discharge healthcare utilization.

Arbuscular mycorrhizal fungi affect the expression of PxNHX gene family, improve photosynthesis and promote Populus simonii×P. nigra growth under saline-alkali stress.

Introduction: Saline-alkali stress seriously endangers the normal growth of Populus simonii×P. nigra. Arbuscular mycorrhizal (AM) fungi can enhance the saline-alkali tolerance of plants by establishing a symbiotic relationship with them. Methods: In this study, a pot experiment was conducted to simulate a saline-alkali environment where Populus simonii×P. nigra were inoculated with Funneliformis mosseae to explore their effects on the saline-alkali tolerance of Populus simonii×P. nigra. Results and Discussion: Our results show that a total of 8 NHX gene family members are identified in Populus simonii×P. nigra. F. mosseae regulate the distribution of Na+ by inducing the expression of PxNHXs. The pH value of poplar rhizosphere soil is reduced, result in the promote absorption of Na+ by poplar, that ultimately improved the soil environment. Under saline-alkali stress, F. mosseae improve the chlorophyll fluorescence and photosynthetic parameters of poplar, promote the absorption of water, K+ and Ca2+, thus increase the plant height and fresh weight of aboveground parts, and promote the growth of poplar. Our results provide a theoretical basis for further exploring the application of AM fungi to improve the saline-alkali tolerance of plants.

Nickel induces hepatotoxicity by mitochondrial biogenesis, mitochondrial dynamics, and mitophagy dysfunction.

Nickel (Ni) is an important and widely hazardous chemical industrial waste. Excessive Ni exposure could cause multi-organs toxicity in human and animals. Liver is the major target organ of Ni accumulation and toxicity, however, the precise mechanism is still unclear. In this study, nickel chloride (NiCl2 )-treatment induced hepatic histopathological changes in the mice, and, transmission electron microscopy results showed mitochondrial swollen and deformed of hepatocyte. Next, the mitochondrial damages including mitochondrial biogenesis, mitochondrial dynamics, and mitophagy were measured after NiCl2 administration. The results showed that NiCl2 suppressed mitochondrial biogenesis by decreasing PGC-1α, TFAM, and NRF1 protein and mRNA expression levels. Meanwhile, the proteins involved in mitochondrial fusion were reduced by NiCl2 , such as Mfn1 and Mfn2, however, mitochondrial fission proteins Drip1 and Fis1 were significantly increased. The up-regulation of mitochondrial p62 and LC3II expression indicated that NiCl2 increased mitophagy in the liver. Moreover, the receptor-mediated mitophagy and ubiquitin (Ub)-dependent mitophagy were detected. NiCl2 promoted PINK1 accumulation and Parkin recruitment on mitochondria. And, the receptor proteins of mitophagy Bnip3 and FUNDC1 were increased in the NiCl2 -treated mice liver. Overall, these results show that NiCl2 could induce mitochondria damage in the liver of mice, and, dysfunction of mitochondrial biogenesis, mitochondrial dynamics and mitophagy involved in the molecular mechanism of NiCl2 -induced hepatotoxicity.

Transcriptome Sequencing of Broussonetia papyrifera Leaves Reveals Key Genes Involved in Flavonoids Biosynthesis.

Broussonetia papyrifera is rich in flavonoids, which have significant antioxidant, antibacterial, and anti-inflammatory activities and certain pharmacological activities. Nevertheless, scarce transcriptome resources of B. papyrifera have impeded further study regarding the process of its production and accumulation. In this study, RNA-seq was utilized to evaluate the gene expression of B. papyrifera leaves at three distinct developmental phases (T1: young leaves, T3: immature leaves, T4: matured leaves). We obtained 2447 upregulated and 2960 downregulated DEGs, 4657 upregulated and 4804 downregulated DEGs, and 805 upregulated and 484 downregulated DEGs from T1 vs. T3, T1 vs. T4, and T3 vs. T4, respectively. Further research found that the following variables contributed to the formation of flavonoids in the leaves of B. papyrifera: Several important enzyme genes involved in flavonoid production pathways have been discovered. The results demonstrated that the dynamic changing trend of flavonoid contents is related to the expression pattern of the vast majority of essential genes in the biosynthetic pathway. Genes associated in energy and glucose metabolism, polysaccharide, cell wall and cytoskeleton metabolism, signal transduction, and protein and amino acid metabolism may affect the growth and development of B. papyrifera leaves, and eventually their flavonoid content. This study's results offer a strong platform for future research into the metabolic pathways of B. papyrifera.

Systematic stress persistence and recovery patterns of rice (Oryza sativa L.) roots in response to molybdenum disulfide nanosheets.

The increasing application of engineered nanomaterials (ENMs) unavoidably leads to environmental release and biological exposure. Understanding the potential hazards of ENMs on crops is essential for appropriate utilization and management. Herein, rice seedlings were hydroponically exposed to molybdenum sulfide (MoS2, a typical ENM) nanosheets at 5-20 mg/L for 7 days and then depurated for another 7 days in a fresh culture medium. Exposure to MoS2 triggered irreversible reductions in root length (by 26.3%-69.9%) and tip number (by 22.2%-66.0%). Integration of biochemical assays, transcriptomic and metabolomics found that oxidative stress induced by MoS2 in roots was persistent, whereas the activation of aquaporins, ionic transportation, and energy synthesis was normalized due to the recovery of nutrient uptake. The down-regulated levels of genes and metabolites associated with peroxidases, hemicellulose synthesis, expansins, and auxins caused persistent structural damages (sclerosis and rupture) of root cell walls. Approximately 64.5%-84.8% of internalized MoS2 nanosheets were degraded, and the successive up-regulation of genes encoding cytochrome P450s and glutathione S-transferases reflected the biotransformation and detoxification of MoS2 in the depuration period. These findings provide novel insights into the persistence and recovery of MoS2 phytotoxicity, which will help advance the risk assessment of MoS2 application on environment.

Construction and validation of the perioral moisture-related skin damage (PMASD) risk prediction model in patients with colorectal cancer.

This study aims to analyse the risk factors of Peristomal Moisture-Associated Skin Damage (PMASD) in colorectal cancer patients, construct a prediction model, and verify its effect. A total of 375 patients who underwent rectal cancer stoma surgery at the Liaoning Cancer Hospital between January and December 2020 were selected according to the inclusion and exclusion criteria. The clinical data were retrospectively analysed for modelling and internal validation (modelling group). According to the same criteria, the clinical data of 242 patients from January and June 2021 were retrospectively analysed for external validation (validation group). Baseline patient data were recorded. Patients in the modelling group were divided into those with and without PMASD based on the occurrence of PMASD during hospitalisation. Logistic regression analysis was used to examine the factors of PMASD and the PMASD nomogram model of colorectal cancer. Internal model validation was performed with the Bootstrap method, using the ROC and H-L goodness of fit test to evaluate the differentiation and calibration of the model. Last, external validation of the model was performed. In the modelling group, 212 patients with colorectal cancer developed PMASD. According to the results of the logistic regression analysis, high fasting plasma glucose and fasting blood glucose (FPG), a history of radiotherapy, the height of the stoma opening (i.e., flat or lower than the skin surface), and skin folds around the stoma are risk factors for PMASD (OR > 1, P < 0.05). The stool shaping and colostomy are protective factors for PMASD in patients with colorectal cancer (OR < 1, P < 0.05). To establish the prediction of colorectal cancer, patient development of PMASD line, graph model, and internal verification was carried out using the Bootstrap method: H-L test P = 0.846, area under curve, area under the ROC curve (0 > 0.75, 95% CI: 0.778-0, AUC = 0.820). The external validation included the H-L test (P = 0.137, AUC [0.862] > 0.75, 95% CI: 0.815-0.909), with the maximum value of the Youden index as the best cut-off value for the model. The ROC curve had a Youden index of 0.559, a sensitivity of 0.877, and a specificity of 0.657. The prompt model area showed good calibration and discrimination. The PMASD in patients with colorectal cancer is affected by defecation traits, the stoma opening height, stoma type, FPG, skin folds around the stoma, and previous radiotherapy history. The nomogram model can provide an effective means to reasonably predict the risk of PMASD in patients with colorectal cancer.

The eco-efficiency evaluation in China's cement industry: A city-level study.

To implement strict environmental targets in China's cement industry into small regions, one should evaluate the city-level eco-efficiency that provides comprehensive instruction. This study establishes a plant-level database with 4000+ production lines located in 341 cities, calculates the energy consumption and CO2, SO2, NOx, and PM emissions, evaluates the eco-efficiency in each city via Slacks-based Measure, and verifies the spatial features of these indicators. Results show that the energy consumption and emissions of the industry are highly concentrated, with ~10 % of the land area contributing to 28.4 %-34.6 % of the total amounts in 2019. The average eco-efficiency value of the clinker calcination and cement grinding processes are 0.761 and 0.714, but the city clusters having low eco-efficiency values are inconsistent with the ones having large energy consumption and emission amounts. The results can contribute to the implementation of the targets such as carbon peaking and pollution cap in China's cement industry.

Design and synthesis of novel quinazolin-4(1H)-one derivatives as potent and selective inhibitors targeting AKR1B1.

Inhibition of aldose reductase (AKR1B1) is a promising option for the treatment of diabetic complications. However, most of the developed small molecule inhibitors lack selectivity or suffer from low bioactivity. To address this limitation, a novel series of quinazolin-4(1H)-one derivatives as potent and selective inhibitors of AKR1B1 were designed and synthesized. Aldose reductase inhibitory activities of the novel compounds were characterized by IC50 values ranging from 0.015 to 31.497 µM. Markedly enhanced selectivity of these derivatives was also recorded, which was further supported by docking studies. Of these inhibitors, compound 5g exhibited the highest inhibition activity with selectivity indices reaching 1190.8. The structure-activity relationship highlighted the importance of N1-acetic acid and N3-benzyl groups with electron-withdrawing substituents on the quinazolin-4(1H)-one scaffold for the construction of efficient and selective AKR1B1 inhibitors.

Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin.

Heparin, a class of glycosaminoglycans (GAGs), is widely used to induce sperm capacitation and fertilization. How heparin induces sperm capacitation remains unclear. Olfactory receptors (ORs) which are G protein-coupled receptors, have been proposed to be involved in sperm capacitation. However, the interaction between ORs and odor molecules and the molecular mechanism of ORs mediating sperm capacitation are still unclear. The present study aimed to explore the underlying interaction and mechanism between heparin and ORs in carrying out the boar sperm capacitation. The results showed that olfactory receptor 2C1 (OR2C1) is a compulsory unit which regulates the sperm capacitation by recognizing and binding with heparin, as determined by Dual-Glo Luciferase Assay and molecular docking. In addition, molecular dynamics (MD) simulation indicated that OR2C1 binds with heparin via a hydrophobic cavity comprises of Arg3, Ala6, Thr7, Asn171, Arg172, Arg173, and Pro287. Furthermore, we demonstrated that knocking down OR2C1 significantly inhibits sperm capacitation. In conclusion, we highlighted a novel olfactory receptor, OR2C1, in boar sperm and disclosed the potential binding of heparin to Pro287, a conserved residue in the transmembrane helices region 7 (TMH7). Our findings will benefit the further understanding of ORs involved in sperm capacitation and fertilization.

The antidiabetic drug metformin aids bacteria in hijacking vitamin B12 from the environment through RcdA.

Years of use of the antidiabetic drug metformin has long been associated with the risk of vitamin B12 (B12) deficiency in type 2 diabetes (T2D) patients, although the underlying mechanisms are unclear. Accumulating evidence has shown that metformin may exert beneficial effects by altering the metabolism of the gut microbiota, but whether it induces human B12 deficiency via modulation of bacterial activity remains poorly understood. Here, we show that both metformin and the other biguanide drug phenformin markedly elevate the accumulation of B12 in E. coli. By functional and genomic analysis, we demonstrate that both biguanides can significantly increase the expression of B12 transporter genes, and depletions of vital ones, such as tonB, nearly completely abolish the drugs' effect on bacterial B12 accumulation. Via high-throughput screens in E. coli and C. elegans, we reveal that the TetR-type transcription factor RcdA is required for biguanide-mediated promotion of B12 accumulation and the expressions of B12 transporter genes in bacteria. Together, our study unveils that the antidiabetic drug metformin helps bacteria gather B12 from the environment by increasing the expressions of B12 transporter genes in an RcdA-dependent manner, which may theoretically reduce the B12 supply to T2D patients taking the drug over time.