Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NO x ), has been acknowledged representing NO bioactivity partially. Dysregulation of NO x had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NO x is unknown. In this study, serum NO 2 − and NO 3 − were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO 2 − and NO 2 − /NO 3 − than the uninfected group (p < 0.0001), with significantly higher NO 3 − levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO 2 − , low NO 2 − /NO 3 − and high NO 3 − may be a potential biomarker of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.

LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non-metastatic and metastatic cancer cell variants of human prostate carcinoma PC-3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V-ATPase, ATP6V0C) and regulate V-ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V-ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V-ATPase expression among different transfected cells and the control. However, V-ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH-dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno-electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC-3M-1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V-ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V-ATPase. Their interaction could play important roles in the apoptosis of tumor cells.

Fungus ball and fungal emphysematous cystitis are two rare complications of fungal urinary tract infection. A 53-year-old male patient presented with these complications caused by Candida tropicalis simultaneously. The predisposing factors were diabetes mellitus and usage of broad-spectrum antibiotics. The fungus ball, measuring 3.5 × 2.0 cm on the left wall of the urinary bladder, shrank significantly to 1.6 × 0.8 cm after 5 days of intermittent irrigation with saline before surgery. With transurethral removal of the fungus ball and antifungal treatment with fluconazole, the patient fully recovered. We conclude that a bladder fungus ball and fungal emphysematous cystitis should always be suspected in patients with diabetes mellitus with uncontrolled funguria and abnormal imaging. Treatment should include a systemic antifungal therapy and thorough surgical removal of the fungus ball. A systemic antifungal therapy combined with a local irrigation with saline or antifungal drugs might help decrease the dissemination of fungemia during an invasive manipulation. Case reportA 53-year-old male was referred to our department in February 2015 with intermittent, but recently aggravated cloudy urine. The symptom had been ongoing for 9 years, sometimes with frequency and urgency. No blood urine or fever was ever reported. To control the symptoms of cystitis, the patient underwent multiple treatments with broadspectrum antibiotics during this 9-year period. Twice, fungus was found in his urine (9 years and 6 years ago).The patient had uncontrolled type II diabetes mellitus for more than a decade. He also suffered from a right kidney stone and underwent a percutaneous nephrolithotomy 18 years ago. Physical examination was unremarkable. A routine urine test showed significantly elevated red blood cells (56.1/HP, normal <4.5/HP) and white blood cells (328.7/HP, normal <5.4/HP). Blood tests were normal, except for an elevated fasting glucose level of 7.7 (range: 3.6-6.1) mmol/L. Sonography revealed a medium-to hypo-echoic bladder tumour, measuring 3.5 × 2.0 cm. It was located on the left wall of the urinary bladder, did not move with posture changes, and had no sign of blood flow (Fig. 1a). A computed tomography (CT) revealed no intravesical mass in either the unenhanced or dual-enhanced phase. Only a very faint filling defect was found in the excretory phase. Moreover, a large round gas collection was found in the bladder, and a 1.1 × 0.9-cm calculus revealed a right distal ureter, leading to mild unilateral hydronephrosis and ureterectasis (Fig. 1b).Urinary cytology showed a large number of hyphae and neutrophil granulocytes. Candida tropicalis was isolated from the urine, but the blood culture was negative. Because a fungus ball secondary to Candida tropicalis was highly suspected at this time, intermittent bladder washouts with saline (2 L per time and 3 times per day) were performed via an indwelling three-cavity urinary catheter. A mass of floccules were flushed out during early irrigation. A rechecked sonography ...

The tumor metastasis suppressor gene 1 (TMSG1), also designated homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2), is a novel tumor metastatic suppressor gene. Although its effects on metastasis have been reported, its biological functions remain unclear. The purpose of this study was to investigate the effects of TMSG1/LASS2 protein on apoptosis and proliferation in human embryonic kidney cell lines HEK293 and 293 T and explore the potential mechanisms. Cell growth, morphology, expressions of apoptotic-related proteins and cell cycle distribution were evaluated in HEK293 and 293 T cells transfected with TMSG1/LASS2 expression plasmids or vector controls. MTT assays showed that overexpression of TMSG1/LASS2 inhibited cell proliferation; and morphological observations and flow cytometric assays with Annexin V/propidium iodide showed TMSG1/LASS2 overexpression increased apoptosis in these cells. Western blot analysis demonstrated that overexpression of TMSG1/LASS2 resulted in the downregulation of Bcl-2, release of cytochrome c from mitochondria, activation of procaspase-9 and procaspase-3, and the cleavage of PARP. Subsequent cell cycle analysis showed that TMSG1/LASS2 overexpression inhibited cell proliferation by mediating the induction of G0/G1 cell cycle arrest. Together, these results confirmed that TMSG1/LASS2 is a potential metastasis suppressor gene, and suggested that the mechanism involved the induction of apoptosis and inhibition of cell proliferation via a caspase-dependent mitochondrial pathway.

We present the first report of histology- and culture-proven Mycobacterium marinum infection diagnosed by next-generation sequencing (NGS). It took &lt;2 days to make a microbiological diagnosis using the Oxford Nanopore Technologies' MinION device, compared to 20 days for the mycobacterium to be isolated from the tissue biopsy. NGS is particularly useful for culture-negative and slow-growing microorganism infections, such as mycobacterial, fungal and partially treated pyogenic bacterial infections. Due to its low equipment cost, short turn-around-time and portable size, the Oxford Nanopore Technologies' MinION device is a useful platform for NGS in routine clinical microbiology laboratories.