Application of metabolomics in urolithiasis:the discovery and usage of succinate

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events.It has been shown that the occurrence of calcium oxalate monohydrate(COM)during stone formation is regulated by crystal growth modifiers.Although crystallization inhibitors have been recognized as a therapeutic modality for decades,limited progress has been made in the discovery of effective modifiers to intervene with stone disease.In this study,we have used metabolomics technologies,a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model.By in-depth mining and analysis of metabolomics data,we have screened five differential metabolites.Through density functional theory studies and bulk crystallization,we found that three of them(salicyluric,gentisic acid and succinate)could effectively inhibit nucleation in vitro.We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones.Notably,succinate,a key player in the tricarboxylic acid cycle,could decrease kidney calcium deposition and injury in the model.Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation,inhibition of cell adhesion and osteogenic differentiation.These findings indicated that succinate may provide a new therapeutic option for urinary stones.

State of polar climate in 2023

The year 2023 has become the warmest year on global record.As the Antarctic and Arctic are sensitive regions to global warming,the climate changes in 2023 in these regions have attracted widespread attention.In this study,using observations,reanalysis and remote sensing data,we reported detailed polar climate changes in 2023,including warming,sea ice,atmospheric composition and extreme events.Antarctic exhibited large east-west regional differences and the coexistence of extreme warm and cold events.In Coats Land,Queen Maud Land and the Antarctic Peninsula,three and seven stations recorded the second and third highest autumn air temperatures in history,respectively.The Amundsen-Scott station experienced extreme warming event in July,with the temperature increasing by 40℃ in one day.Abnormal cooling was evident in the Ross Sea and neighboring regions which were predominantly winter(June-August)cold anomalies,with Marylin Station reaching the lowest winter temperature in history.The Arctic experienced the warmest summer after 1979,with an overall distribution of warm land-cold sea'on annual average.Compared with the 1991-2020 average,the annual air temperature anomalies reached more than 2℃in northern Canada and the Barents Sea-Kara Sea coast.Abnormal high summer temperature caused most severe wildfires in Canada on record and second largest daily cumulative melt area over the Greenland ice Sheet daily post-1979.Polar sea ice continued to decrease rapidly,with minimum sea ice extent in Antarctic and Arctic ranking the first and sixth lowest post-1979.For melt season,Arctic Ocean sea ice began to melt later in 2023 than the 2011-2023 average,and freeze onset was delayed due to high temperatures in summer and autumn.Additionally,the status of polar atmospheric greenhouse gases remains bleak,and major greenhouse gas concentrations continue to increase.The Antarctic ozone hole in 2023 formed approximately 10 d earlier and lasted longer than the 1979-2023 average,with a maximum daily area of 2.6×10^(7)km^(2) on 21 September.This summary of polar climate changes in 2023 will help people better understand global climate change and draw attention to polar regions.

Viral and Bacterial Etiology of Acute Diarrhea among Children under 5 Years of Age in Wuhan, China

Background： Acute diarrhea remains the serious problem in developing countries, especially among children under 5 years of age. Currently, only two or three common diarrhea pathogens were screened at most hospitals in China. The aim of this study was to provide a wide variety of diarrhea pathogens and their antimicrobial resistance patterns in children under 5 years of age. Methods： Totally 381 stool samples collected from Tongji Hospital between July 1, 2014 and June 30, 2015 were tested by culture and/or polymerase chain reaction for eight kinds of bacteria and five kinds of viruses. An antimicrobial sensitivity test was performed using dilution method recommended by the Clinical and Laboratory Standards Institute. Results： Viral infections were mainly identified in infants （0-11 months）, whereas bacterial infections were more prevalent in the age of 24-59 months. About 69.8% of samples were positive for at least one pathogen, 51.7% of samples were virus positive, followed by bacteria positive cases （19.4%）, and 12.6% of cases displayed co-infections with two viruses or a virus and a bacterium. Rotavirus was the most prevalent pathogen, followed closely by norovirus, while Salmonella was the most commonly isolated bacteria, followed by diarrheagenic Escherichia coli （DEC） and Campylobacter. More than 40% of Salmonella spp. and DEC isolates were resistant to first-line antibiotics （ampicillin, trimethoprim-sulfamethoxazole, and tetracycline）. Around 10% of Salmonella spp. isolates were resistant to ceftriaxone and ciprofloxacin simultaneously. Campylobacter spp. displayed high resistance to ciprofloxacin but kept low resistance to azithromycin and doxycycline. Conclusions： The etiology of acute diarrhea varies in children of different age groups. The high frequency of infection with viruses suggests the urgent demand for new viral vaccine development. Proper use of antibiotics in the treatment of acute diarrhea is crucial due to the high level of antibiotic resistance.

Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells

Approximately 25%of patients with congenital heart disease require implantation of patches to repair.However,most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties,which may lead to an increased risk for arrhythmia and heart failure.In this study,we have developed a novel Polyurethane/Small intestinal submucosa patch(PSP)with mechanical and electrical properties similar to those of the native myocardial tissue,and assessed its feasibility for the reconstruction of right ventricular outflow tract.A right ventricular outflow tract reconstruction model was constructed in 40 rabbits.Compared with commercially available bovine pericardium patch,the PSP patch has shown better histocompatibility and biodegradability,in addition with significantly improved cardiac function.To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling,we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells(USCs)which were pretreated with hypoxia.The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization,resulting in better right heart function.Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.

Nickel-Catalyzed Enantioselective Desymmetrizing Aza-Heck Cyclization of Oxime Esters

Densely functionalized chiral nitrogen-containing heterocycles are ubiquitous in bioactive synthetic compounds and natural products.Herein,we report a nickel(Ni)-catalyzed enantioselective desymmetrizing aza-Heck cyclization of oxime esters with a commercially available chiral pyridinebis(oxazoline)(pybox)ligand.This reaction proceeds under mild reaction conditions,tolerates various functional groups,and leads to chiral 2-substituted-3,7a-dihydro-3aH-indoles.