A quantitative theory integrating solid surface hydrophilicity and pore structure features for non-phase-change drying of sewage sludge through gradient increase of ultrahigh filtration pressure.

The sustainable application of thermal sludge drying process is limited by the high energy consumption due to the phase-change latent heat of moisture. This study proposed that the ultrahigh pressure filtration could realize the non-phase-change sludge drying. The lowest water content of 28.12 wt.% was realized by the filtration pressure of 21 MPa for the excess sludge with polyaluminium chloride as the conditioning agent. With the stepwise increase of filtration pressure employed (5-21 MPa), the diameter of solid pores was gradually narrowed to the same order of magnitude with the thickness of vicinal water film (i.e., 1-10 nm). As a result, the capillary water was transformed into the vicinal water, and the solid-water interface interaction played more crucial roles in water occurrence states. However, Hagen-Poiseuille equation was introduced to estimate the pore water outflow based on the pore wall hydrophilicity and the external filtration pressure, which implied that there can be always a sufficiently large driving force to maintain the water outflow rate no matter how the pore diameter is small and the sidewall is hydrophilic. Typically, the fitting results of excess sludge (R2=0.985, p-value<0.01) indicated that the pressure gradient of 2.11 × 109 Pa/m was required to maintain the pore water flow rate of 1.38 × 10-15 m3/s with the median pore diameter of 5.33 × 10-7 m. All these findings broke through the conventional cognition that only thermal drying process can decrease the sludge water content below 60 wt.%, and facilitated energy saving of sludge dewatering process through non-phase-change separation, i.e., ultrahigh pressure filtration.

Intelligent upgrade of waste-activated sludge dewatering process based on artificial neural network model: Core influential factor identification and non-experimental prediction of sludge dewatering performance.

Owing to the extremely complex compositions and origins of waste-activated sludge (WAS), the multiple physiochemical properties of WAS have impacts on its dewaterability, and there is a complex interaction relationship among the multiple physiochemical properties, which makes it difficult to identify the controlling factors on WAS dewaterability. Accordingly, there is still no unified certainty in the appropriate ranges of physiochemical properties for the optimal dewaterability of sludge from different sources, resulting in a lack of clear theoretical basis for technical selection and optimization of sludge dewatering processes. The large consumption of conditioning chemicals and low process efficiency stand for the major deficiency of existing sludge conditioning technologies. This study proposed to use a non-linear, adaptive and self-organizing artificial neural network (ANN) model to integrate the multiple physiochemical properties of WAS affecting its dewaterability, and WAS dewatering performance under certain conditioning schemes could be predicated by ANN model with the multiple physiochemical properties and conditioning operation parameters as the input arguments. Thus, the laborious filtration experiments for screening conditioning chemicals could be replaced by the input adjustment of ANN model. Rooted mean squared error (RMSE) of 6.51 and coefficient of determination (R2) of 0.73 confirmed the satisfied stability and accuracy of established ANN model. Furthermore, the predictor-exclusive method revealed that the exclusion of polar interface free energy decreased most, which reflected the importance of surface hydrophilicity reduction in sludge dewaterability improvement. All the contributions presented here were believed to provide an intelligent insight to improve the experience operation status of WAS dewatering process.

Relationship between nonalcoholic fatty liver disease and bone mineral density in elderly Chinese.

OBJECTIVE: As our society grows older, both bone loss and fatty liver have become important issues. However, the relationship between reduced bone mineral density and fatty liver remains controversial. The purpose of this study was to investigate the relationship between nonalcoholic fatty liver disease and less bone mineral density in the ankles of Chinese people over 65. METHODS: The research included 716 older adults over the age of 65 who underwent a comprehensive health screening. A logistic regression model was used to investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and ankle bone mineral density. RESULTS: A logistic regression model was used to analyze the odds ratios of reduced bone mineral density between patients with fatty liver and controls. In the adjusted model, adjustments were made for age, sex, systolic blood pressure, diastolic blood pressure, overweight rate, history of hypertension, history of diabetes, history of smoking, history of alcohol consumption, fasting glucose, hemoglobin, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, waist circumference, total protein, albumin, and globulin. The adjusted OR (aOR) for reduced bone mineral density was 0.66 [95% confidence interval (CI) = 0.45-0.97, P = 0.034 < 0.05]. In subgroup analysis by age, sex, and BMI, women, age > 75 years, and BIM < 25 were statistically significant. CONCLUSION: This study suggested that NAFLD is associated with a reduced risk of reduced heel bone mass. More research needs to be done to back up the results of this study and look into possible problems.

Crystallization-driven evolution of water occurrence states with implications on dewaterability improvement of waste-activated sludge.

This study proposed to improve the dewaterability of waste-activated sludge (WAS) through crystallization-driven evolution of water occurrence states. Primarily, the feasibility of clathrate hydrate (i.e., CO2 hydrate) formation in WAS was examined. The thermodynamic analysis indicated that the CO2 hydrate formation with the excessive water in WAS followed pseudo-first-order kinetics, and fit of the data yielded a kobs value of 3.905 × 10-5 L∙mol-1∙s-1 for 274.15 K. With the water conversion efficiency of 100%, the crystallization-dissociation process of CO2 hydrate significantly improved the dewaterability of WAS in term of capillary suction time (CST) decreasing from 251.5 s to 57.4 s. Also, the relief of gas pressure can induce the hydrate dissociation, which creates a novel way to recycle CO2 gas and save the consumption of chemicals required by sludge dewatering process. Regarding the mechanism of hydrates-based sludge dewatering, the evolution of water occurrence state was investigated. The in-situ synchrotron X-ray computed microtomography visually analyzed the micro-scale porosity and interstitial water of WAS flocs. The model of three-dimensional pore structure was established and the porosity parameters of solid aggregates were determined. It was found that the volume of connected pores and the total pore volume fraction of solid compositions increased. But the mean volume and mean area of isolated pores simultaneously decreased by 14.6% and 12.4%, respectively, which meant that the steric hindrance caused by isolated pores was weakened due to the reduced solid-water contact area. In addition, the crystallization of water caused the reformation of conformation arrangement of vicinal water and solid molecules, which highly organized the water molecules into the crystal structure. Accordingly, an estimation method for vicinal water layer thickness was developed based on atom force microscope. The thickness of vicinal water layer was found to be reduced by 77.4% and the hydration repulsion among solid compositions was correspondingly weakened, which facilitated the aggregation of solid compositions, and the relatively separated hydrate phase and solid phase could be formed. All the above results open up a novel strategy for enhanced water-solid separation of WAS through the crystallization-driven evolution of water occurrence states. As distinguished from the conventional approaches, the hydrates-based sludge dewatering enhances the water-solid separation only with regulating the spatial arrangement of water-solid molecules, but without altering the chemical compositions. Thus, more chances can be created to increase the environmentally friendly attributes related to WAS dewatering.

miR-1-3p Inhibits Osteosarcoma Cell Proliferation and Cell Cycle Progression While Promoting Cell Apoptosis by Targeting CDK14 to Inactivate Wnt/Beta-Catenin Signaling.

Osteosarcoma (OS) is a common bone malignancy and is diagnosed frequently in children and young adults. According to previous RNA sequencing, miR-1-3p is downregulated in OS clinical samples. Nevertheless, the functions of miR-1-3p in OS cell process and the related mechanism have not been revealed yet. In the current study, miR-1-3p expression in OS tissues and cells were evaluated using quantitative polymerase chain reaction. CCK-8 assays were conducted to measure OS cell viability in response to miR-1-3p overexpression. Colony forming assays and EdU staining were conducted for measurement of cell proliferation, and flow cytometry analysis was performed to determine cell apoptosis and cell cycle progression. Protein levels of apoptotic markers, beta-catenin, and Wnt downstream targets were quantified using western blotting. The binding relation between miR-1-3p and cyclin dependent kinase 14 (CDK14) was validated utilizing luciferase reporter assays. Experimental results revealed that miR-1-3p expression was decreased in OS tissues and cells. Additionally, miR-1-3p inhibited cell proliferation and cell cycle progression while enhancing OS cell apoptosis. Moreover, miR-1-3p directly targeted CDK14 and inversely regulated CDK14 expression in OS cells. Furthermore, miR-1-3p inactivated the Wnt/beta-catenin signaling. CDK14 overexpression partially rescued the inhibitory impact of miR-1-3p on OS cell growth. Overall, miR-1-3p inhibits OS cell proliferation and cell cycle progression while promoting cell apoptosis by targeting CDK14 and inactivating the Wnt/beta-catenin signaling.

Raspberry-like AgBiS2@PVP nanoparticles for enhanced sonodynamic and chemodynamic cancer therapy.

Sonodynamic therapy (SDT) is a non-invasive treatment, preferred by many researchers. Ultrasound is applied to tumor lesions, enriched with a sound sensitizer. The activation of the sound sensitizer produces reactive oxygen species (ROS), which kill the tumor cells. In this study, raspberry-like AgBiS2@PVP nanoparticles (NPs) were prepared, which were modified with polyvinylpyrrolidone (PVP). Finally, AgBiS2@PVP NPs with 261 nm diameter and a suitable band gap were successfully synthesized. These NPs could play a role in SDT by generating ROS when induced by ultrasonic stimulation. Moreover, the AgBiS2@PVP NPs could also catalyze H2O2 in the tumor microenvironment to produce ˙OH, equipping the NPs with chemodynamic therapy (CDT) properties. In vivo and in vitro experiments suggested that, compared to the single treatments, the combination of SDT and CDT had a clearer inhibitory effect on tumor cells.

Disruption of REC8 in Meiosis I led to watermelon seedless.

In triploid watermelon (Citrullus lanatus), the homologous chromosomes of germ cells are disorder during meiosis, resulting in the failure of seeds formation and producing seedless fruit. Therefore, mutating the genes specifically functioning in meiosis may be an alternative way to achieve seedless watermelon. REC8, as a key component of the cohesin complex in meiosis, is dramatically essential for sister chromatid cohesion and chromosome segregation. However, the role of REC8 in meiosis has not yet been characterized in watermelon. Here, we identified ClREC8 as a member of RAD21/REC8 family with a high expression in male and female flowers of watermelon. In situ hybridization analysis showed that ClREC8 was highly expressed at the early stage of meiosis during pollen formation. Knocking out ClREC8 in watermelon led to decline of pollen vitality. After pollinating with foreign normal pollen, the ovaries of ClREC8 knockout lines could inflate normally but failed to form seeds. We further compared the meiosis chromosomes of pollen mother cells in different stages between the knockout lines and the corresponding wild type. The results indicated that ClREC8 was required for the monopolar orientation of the sister kinetochores in Meiosis I. Additionally, transcriptome sequencing (RNA-seq) analysis between WT and the knockout lines revealed that the disruption of ClREC8 caused the expression levels of mitosis-related genes and meiosis-related genes to decrease. Our results demonstrated ClREC8 has a specific role in Meiosis I of watermelon germ cells, and loss-of-function of the ClREC8 led to seedless fruit, which may provide an alternative strategy to breed cultivars with seedless watermelon.

Mechanism insights into liquid polarity regulation for enhanced dewatering of waste-activated sludge: Specifically focusing on the solid-liquid affinity reduction depending on phase-transfer and conformational features of amphiphilic protein.

This study proposed that decreasing liquid polarity could weaken the intermolecular polar force at solid-liquid interface of waste-activated sludge (WAS). Accordingly, a process for enhanced sludge dewatering through liquid polarity regulation was established. The liquid polarity was quantified by dielectric constant and the decrease of liquid dielectric constant below 50 was found to significantly improve the solid-liquid separation performance of WAS in terms of filterability by >70%. The differential scanning calorimeter (DSC) coupled with mass spectrum (MS) identified that 60 °C was the appropriate temperature for liquid amendment (i.e., acetonitrile) recovery from filtered sludge cake, and the corresponding energy consumption was calculated to be at most 799.0 J/g, which was substantially lower than that of water evaporation by sludge drying. The NaCl addition with 75% of saturated concentration could non-thermally recover 91.7 ± 4.9% of acetonitrile amendment from filtrate by salting-out. The great potentials in energy saving and recycle of chemicals make the newly proposed approach act as alternatives for the conventional process (i.e., mechanically dewatering + drying). Regarding the mechanism of liquid polarity regulation for enhanced WAS dewatering, the solid-liquid interfacial free energy was found to be reduced by 39.4% with the liquid dielectric constant decreasing from 78.50 to 41.00. Also, Tandem Mass Tags (TMT) proteomics tracked the phase-transfer of amphiphilic proteins with decreasing liquid polarity, which found that the solubilization of proteins involved in the Gene Ontology (GO) classifications of "membrane protein complex" and "membrane protein complex/outer membrane" could facilitate the enhanced solid-liquid separation of WAS. The conformational analysis on those differential proteins was further conducted to reveal the structure attributes of amphiphilic proteins for the phase-transfer feature. The proteins with more exposed amino acid residues (i.e., average solvent accessibility index over 1.8) tended to dissolve in the liquid phase with lower polarity, which was accompanied with the reduced interfacial free energy of WAS. On the contrary, the proteins with buried amino acid residues (e.g., the central hydrophobic ß-sheet is surrounded by the hydrophilic α-helix) precipitated in the solid phase with the decreasing liquid polarity. All these findings are expected to create a novel option for dewatering WAS with recyclable liquid conditioning agents, and provide the improved mechanistic insights into the migration of interfacial compositions controlling the dewaterability of WAS.

Detection of Fe3+ and Hg2+ Ions by Using High Fluorescent Carbon Dots Doped With S And N as Fluorescence Probes.

In this paper, carbon quantum dots (N-S-CDs) containing sulfur and nitrogen were synthesized using citric acid and thiourea. The average particle size of N-S-CDs is 8 nm. The N-S-CDs surface contains various of functional groups, which has good water solubility. The fluorescence quantum yield of N-S-CDs is as high as 36.8%. N-S-CDs emits strong blue fluorescence in aqueous solution and has good photostability in neutral and alkaline NaCl solution. N-S-CDs has unique selectivity and high sensitivity to Fe3+ and Hg2+ ions, and the lowest detection limits are 1.4 µM and 0.16 µM, respectively. Under the interference of other metal ions, Fe3+ and Hg2+ ions can still effectively and stably quench the fluorescence of N-S-CDs. In addition, in the detection of actual samples, N-S-CDs can effectively detect Fe3+ and Hg2+ ions in tap water and lake water.

Effects of Sinapic Acid Combined with Cisplatin on the Apoptosis and Autophagy of the Hepatoma Cells HepG2 and SMMC-7721.

Sinapic acid (Sa) is a small-molecule phenolic acid compound predominant in fruits, vegetables, and grains. This study investigated the antitumor effects of cisplatin (DDP) combined with Sa (Sa/DDP) on the hepatic cancer cells (HCC), HepG2 and SMMC-7721. The HepG2 and SMMC-7721 cells were treated with Sa or Sa/DDP, and the cell proliferation and cell cycle were detected using the MTT assay. The cell migration was detected using the transwell and scratch assays, while apoptosis and autophagy were detected using Hoechst, MDC, and Annexin V-FITC/PI staining. The protein expression was quantitated using the western blot. Sa/DDP was found to not only inhibit cancer cell proliferation and migration but also induce cell apoptosis. Simultaneously, the Sa/DDP combination was found to activate autophagy, and the HCQ autophagy inhibitor enhanced the apoptosis in the Sa/DDP-induced liver cancer cells. The combined use of Sa and DDP makes it an attractive adjuvant therapy strategy for tumors, establishing the prospect of phenolic acid compounds for the adjuvant treatment of hepatocellular carcinoma.

Altered Fecal Microbiota Composition in Older Adults With Frailty.

Objective: Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome. Methods: We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers. Results: Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability. Conclusions: Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.

The Rapid Cytological Process of Grain Determines Early Maturity in Weedy Rice.

Shorter grain-filling period and rapid endosperm development endow weedy rice (WR) with early maturity compared to cultivated rice (CR). However, the role of the cytological features and antioxidative enzyme system during grain development are largely unexplored. We selected four biotypes of WR and their associated cultivated rice (ACR) types from different latitudes to conduct a common garden experiment. The difference in the cytological features of endosperm between WR and ACR was compared by chemical staining, and the cell viability and nuclear morphometry of endosperm cells were observed by optical microscopy. Furthermore, antioxidative enzyme activity was measured during grain filling. Anatomic observation of endosperm shows that the development process of endosperm cell in WR was more rapid and earlier than that in ACR. The percentage of degraded nuclei of WR was 2-83% more than that of ACR. Endosperm cells in WR lost viability 2-6 days earlier than those in ACR. The antioxidant enzyme activity of WR was lower than that of ACR during grain filling. The ability of WR to scavenge reactive oxygen species (ROS) was weaker than that of ACR, which may contribute to the rapid cytological process in the endosperm cells of WR. The rapid cytological process and weaker ability to scavenge ROS in endosperm cells may contribute to early maturity in WR.

Gene Flow Risks From Transgenic Herbicide-Tolerant Crops to Their Wild Relatives Can Be Mitigated by Utilizing Alien Chromosomes.

Integration of a transgene into chromosomes of the C-genomes of oilseed rape (AACC, 2n = 38) may affect their gene flow to wild relatives, particularly Brassica juncea (AABB, 2n = 36). However, no empiric evidence exists in favor of the C-genome as a safer candidate for transformation. In the presence of herbicide selections, the first- to fourth-generation progenies of a B. juncea × glyphosate-tolerant oilseed rape cross [EPSPS gene insertion in the A-genome (Roundup Ready, event RT73)] showed more fitness than a B. juncea × glufosinate-tolerant oilseed rape cross [PAT gene insertion in the C-genome (Liberty Link, event HCN28)]. Karyotyping and fluorescence in situ hybridization-bacterial artificial chromosome (BAC-FISH) analyses showed that crossed progenies from the cultivars with transgenes located on either A- or C- chromosome were mixoploids, and their genomes converged over four generations to 2n = 36 (AABB) and 2n = 37 (AABB + C), respectively. Chromosome pairing of pollen mother cells was more irregular in the progenies from cultivar whose transgene located on C- than on A-chromosome, and the latter lost their C-genome-specific markers faster. Thus, transgene insertion into the different genomes of B. napus affects introgression under herbicide selection. This suggests that gene flow from transgenic crops to wild relatives could be mitigated by breeding transgenic allopolyploid crops, where the transgene is inserted into an alien chromosome.

The Outlook of the Development of Innovative Products from Biocompatible Natural Spider Silk in the Beauty Thread-Lifting Industry.

Embedding thread lift rhytidectomy, also known as "thread lifting" in China, with the natures of simple operation, less trauma and quick recovery, is progressively used in clinical practice as a new technology of face lifting. Herewith, a brief introduction of the previous advances of thread lifting techniques and materials in the facial beauty industry, combined with the discussion on various types of sutures, common complications, and the site of actions were provided. The main limitations of present thread lifting material include: (1) the use of non-absorbable sutures is liable to cause allergies and a series of complications; (2) the absorbable sutures are easily degradation, and people need to reshape in a relatively short period. Therefore, the high biocompatible spider silk was proposed as a novel material of thread lifting suture and related devices, the advantages and preliminary achievements on spider silk were also addressed.

Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.

Expression and function of miR-155 in rat synovial fibroblast model of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint synovial inflammation and is a challenge for researchers and clinicians. MicroRNAs (miRNAs/miRs) represent a group of small non-coding RNA molecules that post-transcriptionally regulate mRNA expression and are involved in various diseases, including cancer, autoimmune and metabolic diseases, as well as neurological disorders. In the present study, various experiments were performed to investigate the effects and underlying mechanism of miR-155 in RA using rat synoviocytes induced by lipopolysaccharide (LPS) to model rheumatoid arthritis. It was revealed that synovial fibroblasts exhibited significantly higher miR-155 mRNA levels than the control group. Compared with the RA group, the viability of synovial fibroblasts was significantly decreased in the miR-155 mimics + RA group, but markedly increased in the miR-155 inhibitor + RA group. Compared with that in the RA + NC mimic or RA + NC inhibitor groups, the apoptosis of synovial fibroblasts increased significantly in the miR-155 mimics + RA group, but was significantly decreased in the miR-155 inhibitor + RA group. The miR-155 mimics + RA group exhibited higher expression levels of ß-catenin, matrix metalloproteinase 7 and cyclin D1 compared with the miR-155 inhibitor + RA group, and the glycogen synthase kinase protein levels was lower compared with the miR-155 inhibitor + RA group. In brief, it was inferred that the Wnt signaling pathway is involved in the miR-155-associated inhibition of RA synovial fibroblast viability and induction of cell apoptosis. Inhibition of miR-155 may be an effective treatment for RA through regulation of the Wnt signaling pathway to reduce cell apoptosis and enhance cell viability.

Vagus Nerve Stimulation Attenuates Acute Skeletal Muscle Injury Induced by Ischemia-Reperfusion in Rats.

Vagus nerve stimulation (VNS) has been shown to attenuate ischemia-reperfusion (I/R) injury in multiple organs. The present study aimed at investigating whether VNS could exert protective effects against I/R injury in the skeletal muscle. Male Sprague-Dawley rats were randomly divided into 3 groups: the control, I/R, and I/R+VNS groups. The skeletal muscle I/R (SMI/R) model was induced by occlusion of the left femoral artery for 2.5 hours followed by reperfusion for 2 hours. The vagal nerve trunk was separated, and VNS was performed during the whole I/R process. The intensity of VNS was optimized in each rat to obtain a 10% reduction in the heart rate relative to the value before stimulation. After the experiment, the blood sample and left gastrocnemius muscle tissues were collected for histological examination, biochemical analysis, and molecular biological detection. During the I/R process, VNS significantly reduced cellular apoptosis, necrosis, and inflammatory cell infiltration compared to sham VNS. The VNS treatment also decreased the inflammatory response, alleviated oxidative stress, and improved vascular endothelial function (p < 0.05 for each). In contrast, the I/R group showed an opposite effect compared to the control group. The present study indicated that VNS could protect against SMI/R injury by suppressing excessive inflammation, alleviating oxidative stress, and preserving vascular endothelial function.

Awareness and Attitudes Regarding Industrial Food Fortification in Mongolia and Harbin.

This study assessed awareness and attitudes regarding industrial food fortification among adults in urban and rural Mongolia, and the city of Harbin, China. Between 2014 and 2017, surveys were collected from healthy men and women aged ≥18 years (182 Harbin residents and 129 urban and rural Mongolians participating in a nationwide nutrition survey in Mongolia). Survey reproducibility was assessed among 69 Mongolian participants to whom it was administered twice (summer and winter). Findings revealed that only 19% of rural and 30% of urban Mongolians, and 48% of Harbin residents were aware that industrial fortification is practiced in their countries. For most food groups evaluated, at least half of Mongolians and less than half of Harbin residents thought fortification was government-mandated (only the addition of iodine with salt is actually mandated in both countries). Fifty-five percent of rural and urban Mongolians favored mandatory fortification of foods, 14% disapproved of it, and 31% were uncertain (compared with 25%, 38%, and 37% respectively in Harbin). Upon learning that the primary purpose of adding vitamin D to milk is to prevent rickets, 75% of Mongolians but only 18% of Harbin residents favored mandatory fortification, while 42% of Harbin residents favored voluntary fortification (compared with <10% of Mongolians). In conclusion, in Mongolia and Harbin, awareness and understanding of food fortification is low, as is receptivity toward mandatory fortification. Health promotion and social marketing should be designed to create an enabling environment for increasing supply and demand of fortified foods, in support of upcoming program implementation in Mongolia and potential future legislation in northeern China.

Overexpressed eNOS upregulates SIRT1 expression and protects mouse pancreatic ß cells from apoptosis.

Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic ß cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated. Furthermore, the cell proliferation and cell apoptosis of the Min6 cells were evaluated, using a cell counting kit-8 assay and flow cytometry, respectively. The results suggested that overexpressed eNOS promoted cell proliferation and inhibited cell apoptosis in Min6 cells. The interaction between eNOS and SIRT1 was explored through co-immunoprecipitation, and it found that there was a strong interaction between eNOS and SIRT1. In conclusion, overexpressed eNOS may induce SIRT1 activation, which is implied to play a protective role in Min6 cells, and eNOS may be a new therapeutic target for diseases such as type 2 diabetes.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.

BACKGROUND: Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management. METHODS: We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8-year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. RESULTS: In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1-170) and to resolution was 32 days (2-809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four cases resolved and one was fatal. CONCLUSION: Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. IMPLICATIONS FOR PRACTICE: With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune-related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab.