Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure

Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure.Mesothelial cell loss is an initiating event for peritoneal fibrosis.We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E,driving downstream inflammatory responses,including the activation of macrophages.Moreover,pyroptosis is associated with elevated vascular endothelial growth factor A and C,two key factors in vascular angiogenesis and lymphatic vessel formation.GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure.Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action,and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy.Mechanistically,melatonin treatment maintains mitochondrial integrity in mesothelial cells,meanwhile activating m TOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate.These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress.Thus,Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

Performance testing of a heat pump system with auxiliary hot water under different ambient temperatures

In recent decades,solar collector and heat pump combinations have been widely applied to supply heat and hot water,such as in heat supply and power generation for domestic and commercial buildings and relevant applications in the manufacturing and agricultural industries.However,the solar-assisted heat pumps already in extensive use may undergo system performance deterioration in a cold environment.To solve this problem,we designed a heat pump system assisted with hot water where a water medium was used to store energy to assist the operation of the heat pump at low temperatures.Three factors were comprehensively considered:the opening degree of the electronic expansion valve,the temperature of the low-temperature heat source,and the auxiliary hot water temperature.Crossover experiments were designed with three levels for each factor,and 36 groups of experiments were carried out.The results showed that as the auxiliary hot water temperature increased,the heating capacity and the coefficient of performance also increased.Thus,the overall working efficiency of the system improved.According to the orthogonal test,the most important influencing factor of system performance was the auxiliary hot water temperature,followed by the ambient temperature and opening degree of the electronic expansion valve.These results fully demonstrated that the addition of auxiliary hot water could dramatically improve system performance.In addition,optimization of the opening degree of the electronic expansion valve produced different results,indicating that the optimal value ranged from 50%−75%.

A de novo assembled genome of the Tibetan Partridge (Perdix hodgsoniae) and its high-altitude adaptation

The Tibetan Partridge(Perdix hodgsoniae)is an endemic species distributed in high-altitude areas of 3600–5600 m on the Qinghai–Tibet Plateau.To explore how the species is adapted to the high elevation environment,we as-sembled a draft genome based on both the Illumina and PacBio sequencing platforms with its population genetics and genomics analysis.In total,134.74 Gb short reads and 30.81 Gb long reads raw data were generated.The 1.05-Gb assembled genome had a contig N50 of 4.56 Mb,with 91.94%complete BUSCOs.The 17457 genes were annotated,and 11.35%of the genome was composed of repeat sequences.The phylogenetic tree showed that P.hodgsoniae was located at the basal position of the clade,including Golden Pheasant(Chrysolophus pictus),Common Pheasant(Phasianus colchicus),and Mikado Pheasant(Syrmaticus mikado).We found that 1014,2595,and 2732 of the 6641 one-to-one orthologous genes were under positive selection in P.hodgsoniae,detected using PAML,BUSTED,and aBSREL programs,respectively,of which 965 genes were common under positive selec-tion with 3 different programs.Several positively selected genes and immunity pathways relevant to high-altitude adaptation were detected.Gene family evolution showed that 99 gene families experienced significant expansion events,while 6 gene families were under contraction.The total number of olfactory receptor genes was relatively low in P.hodgsoniae.Genomic data provide an important resource for a further study on the evolutionary history of P.hodgsoniae,which provides a new insight into its high-altitude adaptation mechanisms.

Clinical characteristics and pathogenic analysis of lower respiratory tract infections in advanced lung cancer patients with different treatment modalities

Objective:To clarify the clinical characteristics and pathogenic analysis after lower respiratory tract infection in patients with advanced lung cancer under different treatments.Methods:A retrospective analysis was adopted to collect 94 cases of patients with advanced lung cancer combined with lower respiratory tract infection from January 1,2018 to December 1,2020.Seventy-four cases were male and 20 cases were female.According to the different treatments,the patients were divided into 43 cases in the chemotherapy group and 51 cases in the chemoradiotherapy group.The pathogenic and serological indexes were compared between the two groups to provide ideas for the application of antibiotics.Results:In the comparison of general clinical data,the chemotherapy group had a shorter hospital stay than the chemoradiotherapy group and a higher body mass index level than the chemoradiotherapy group(p<0.05).In the comparison of serological indicators,procalcitonin,high-sensitive Creactive protein,erythrocyte sedimentation rate,and neutrophil percentage were lower in the chemotherapy group,and the lymphocyte was higher than that in the chemoradiotherapy group(p<0.05).There was no difference in hemoglobin,albumin,creatinine,and alanine transaminase between the two groups(p>0.05).In the comparison of pathogenicity,the chemotherapy group was more likely to have combined viral infections,while the chemoradiotherapy group was more likely to have Gram-negative bacterial infections(p<0.05).There was no difference between the two groups in terms of fungal infections(p>0.05).Besides,the chemoradiotherapy group was more likely to have combined infections(p>0.05).Conclusion:Patients with advanced lung cancer treated with chemoradiotherapy have a relatively poor prognosis after developing lower respiratory tract infections and are more likely to have mixed infections.Antibiotics need to be applied as early as possible.The common pathogens should be covered.Antiviral and antifungal drugs can be added as appropriate,and drug sensitivity tests should be completed as early as possible.