The establishment of an experimental animal model would be useful to study the mechanism of kidney stone formation. A calcium kidney stone model in rats induced by ethylene glycol has been used for research; however, to investigate the genetic basis affecting kidney stone formation, which will contribute to preventive medicine, the establishment of a kidney stone model in mice is essential. This study indicates the optimum conditions for inducing calcium oxalate stones in normal mouse kidney. Various doses of oxalate precursors, ethylene glycol, glycolate and glyoxylate, were administered either by free drinking or intraabdominal injection for 2 months as a preliminary study. Stone formation was detected with light microscopy, polarized light optical microscopy and electron microscopy. Stone components were detected with X-ray diffraction analysis. The expression of osteopontin (OPN), a major stone-related protein, was detected with immunohistochemical staining, in situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Kidney stones were not detected in ethylene glycol- or glycolate-treated groups even at the highest dose of LD(50). Whereas, numerous kidney stones were detected in glyoxylate-treated mice (more than 60 mg/kg) at 3, 6 and 9 days after glyoxylate were administered intraabdominally. However, the number of kidney stones decreased gradually at day 12, and was hardly detected at day 15. The stone component was further analyzed as calcium oxalate monohydrate. A dramatic increase in the expression of OPN was observed by the administration of glyoxylate. We established a mouse kidney stone experimental system in this study. The difficulty of inducing kidney stones suggested that mice have greater intrinsic ability to prevent stone formation with hyperoxaluric stress than rats. The differing response to hyperoxaluric stress between mice and rats possibly contributes to the molecular mechanism of kidney stone formation and will aid preventive medicine in the future.

We combine field observations, microcosm, stoichiometry, and molecular and stable isotope techniques to quantify N2O generation processes in an intensively managed low carbon calcareous fluvo-aquic soil. All the evidence points to ammonia oxidation and linked nitrifier denitrification (ND) being the major processes generating N2O. When NH4+-based fertilizers are applied the soil will produce high N2O peaks which are inhibited almost completely by adding nitrification inhibitors. During ammonia oxidation with high NH4+ concentrations (>80 mg N kg−1) the soil matrix will actively consume oxygen and accumulate high concentrations of NO2−, leading to suboxic conditions inducing ND. Calculated N2O isotopomer data show that nitrification and ND accounted for 35–53% and 44–58% of total N2O emissions, respectively. We propose that slowing down nitrification and avoiding high ammonium concentrations in the soil matrix are important measures to reduce N2O emissions per unit of NH4+-based N input from this type of intensively managed soil globally.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is a major global health threat. We aimed to describe the characteristics of liver function in patients with SARS-CoV-2 and chronic hepatitis B virus (HBV) co-infection. METHODS: We enrolled all adult patients with SARS-CoV-2 and chronic HBV co-infection admitted to Tongji Hospital from February 1 to February 29, 2020. Data of demographic, clinical characteristics, laboratory tests, treatments, and clinical outcomes were collected. The characteristics of liver function and its relation with the severity and prognosis of disease were described. RESULTS: Of 105 SARS-CoV-2 and chronic HBV co-infected patients, elevated levels of liver test were seen in several patients at admission, including elevated levels of alanine aminotransferase (22, 20.95%), aspartate aminotransferase (29, 27.62%), total bilirubin (7, 6.67%), gamma-glutamyl transferase (7, 6.67%), and alkaline phosphatase (1, 0.95%). The values of the indices mentioned above increased substantially during hospitalization (all P < .05). Fourteen (13.33%) patients developed liver injury. Most of them (10, 71.43%) recovered after 8 (range 6-21) days. Notably, 4 (28.57%) patients rapidly progressed to acute-on-chronic liver failure. The proportion of severe COVID-19 was higher in patients with liver injury (P [ .042). Complications including ACLF, acute cardiac injury and shock happened more frequently in patients with liver injury (all P < .05). The mortality was higher in individuals with liver injury (28.57% vs 3.30%, P [ .004). CONCLUSION: Liver injury in patients with SARS-CoV-2 and chronic HBV co-infection was associated with severity and poor prognosis of disease. During the treatment of COVID-19 in chronic HBVinfected patients, liver function should be taken seriously and evaluated frequently.

Abstract. Monoclonal antibody biotherapeutics are often administered by subcutaneous (SC) injection. Due to dose requirements and formulation limitations, SC injections >1 mL are often required. We used a viscous placebo buffer (5 cP), characteristic of a high-concentration antibody formulation, to investigate the effect of dose volume and injection rate on the tolerability of higher-volume SC injections. In this randomized, crossover, single-center study, 48 healthy adults received one 1.2-mL bolus injection over 5 s and three 3.5-mL injections over 1, 4, and 10 min in different abdominal quadrants, with each injection separated by approximately 2 h. The primary objective was to compare pain scores associated with the injections, immediately after administration and 1 h later, using a 100-mm visual analog scale (VAS). Secondary objectives included assessment of adverse events, including injection site reactions and swelling. Mean age was 38.4 (11.6) years and 20 subjects (42%) were female. Lowest mean VAS score was for the 10-min (6.83 mm) and highest for the 1-min injection (19.13 mm). One hour after administration, mean VAS scores were <3.5 mm for all injections. Swelling was similar among the three 3.5-mL injections. After needle removal, leakage occurred following 14 (29%) 1.2-mL injections, eight (17%) 4-min injections, five (10%) 1-min injections, and four (8%) 10-min injections. Fifteen subjects (31%) experienced an adverse event, none of which was serious, fatal, or led to study discontinuation. All injection durations were well tolerated, suggesting a single large-volume SC injection of a biotherapeutic agent could be used instead of multiple injections.

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Alkaloids are nitrogen-containing heterocyclic compounds typically isolated from plants. They represent one of the most important types of natural products because of their large number and structural diversity and complexity. Based on their chemical core structures, alkaloids are classified as isoquinolines, quinolines, indoles, piperidine alkaloids, etc. In-depth analyses of alkaloids have revealed their antibacterial activities. To date, due to the widespread use of antibiotics, the problem of drug-resistant bacterial infections has been gradually increasing, which severely affects the clinical efficacy of antibacterial therapies and patient safety. Therefore, significant research efforts are focused on alkaloids because they represent a potentially new type of natural antibiotic with a wide antibacterial spectrum, rare adverse reactions, and a low tendency to produce drug resistance. Their main antibacterial mechanisms include inhibition of bacterial cell wall synthesis, change in cell membrane permeability, inhibition of bacterial metabolism, and inhibition of nucleic acid and protein synthesis. This article reviews recent reports about the chemical structures and the antibacterial activities and mechanisms of alkaloids. The purpose is to solve the problem of bacterial resistance and to provide a certain theoretical basis and research ideas for the development of new antibacterial drugs.

BackgroundLung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. The main obstacle to early diagnosis or monitoring of patients at high risk of poor survival has been the lack of essential predictive biomarkers.MethodsRNA-sequencing was performed on LUAD affected tissue and paired adjacent to noncancerous tissue samples and Gene Expression Omnibus dataset GSE19188 and GSE33532 were used to obtain an intersection of differential expressed genes and construct a protein–protein interaction network to get hub genes. Then corresponding overall survival information of two cohorts of LUAD patients from our hospital and The Cancer Genome Atlas project-LUAD were included in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes database and Gene Ontology were carried out to study the signature mechanism.ResultsIn our study, we identified eight candidate genes (DLGAP5, KIF11, RAD51AP1, CCNB1, AURKA, CDC6, OIP5 and NCAPG) closely related to survival in LUAD. A linear prognostic model of the eight genes was constructed and weighted by the regression coefficient (β) from the multivariate Cox regression analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and high-risk groups. The prognostic ability of the signature was validated in LUAD patients at our hospital. Patients assigned to the high-risk group exhibited poor overall survival compared to patients in the low-risk group. Finally, functional enrichment analysis showed that cell division played a vital role in the development of LUAD.ConclusionThe study identified an mRNA signature including eight genes, which may serve as a potential prognostic marker of LUAD.