Parental experiences orchestrate locust egg hatching synchrony by regulating nuclear export of precursor miRNA.

Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1-PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a "CU motif"-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.

Coal humus acid functionalized high stability fluorescent copper nanoclusters for tumor identification by sequential off-on-off monitoring tryptophan and Hg2.

The abnormalities of Tryptophan (Trp) and mercury ions (Hg2+) not only easily activate diseases, including mental illness and cancer, but also seriously affect human wellbeing. Fluorescent sensors are profoundly attractive options for identifying amino acids and ions; however, most sensors remain challenging due to the multipliable cost and deviation from the asynchronous quenching detection. In particular, fluorescent copper nanoclusters with high stability that quantitatively monitoring Trp and Hg2+ successively have seldom been reported. Herein, we employ coal humus acid (CHA) as a protective ligand and successfully construct weak cyan fluorescent copper nanoclusters (CHA-CuNCs) by a rapid, environmentally benign and cost-effective method. Significantly, the fluorescence of CHA-CuNCs is obviously improved by introducing Trp, because the indole group of Trp enhances the radiative recombination and aggregation-induced emissions. Interestingly, CHA-CuNCs not only realizes the highly selective and specific detection of Trp with a linear range of 25-200 µM and a detection limit of 0.043 µM based on the turn-on fluorescence strategy, but also quickly achieves the consecutive turn-off detection of Hg2+ due to the chelation interaction between Hg2+ and pyrrole heterocycle in Trp. Moreover, this method is successfully applied in the analysis of Trp and Hg2+ in real samples. Furthermore, the confocal fluorescent imaging of tumor cells demonstrates that CHA-CuNCs can be used for bioimaging and cancer cell recognition with Trp and Hg2+ abnormalities. These findings provide new guidance for the eco-friendly synthesis of CuNCs with eminent sequential off-on-off optical sensing property, indicating good prospects in biosensing and clinical medicine applications.

Ratiometric fluorescent detection of sulfide ions in Radix Codonopsis and living cells based on PVP-supported gold/copper nanoclusters with tunable dual emission.

Herein, a novel fluorometric-sensor with dual-emission system was constructed on the basis of polyvinylpyrrolidone (PVP) and 2-mercaptobenzothiazole (MBT) co-functionalized gold/copper nanoclusters (PVP/MBT-Au@CuNCs) by a facile and eco-friendly one-pot approach. The sensor exhibited ratiometric fluorescence emission (F590 nm/F422 nm) for visual and selective detection of S2- with a sensitive detection limit of 11.9 nM. Besides, fluorescence quenched sensing of S2- was chalked up by a quickly selectivity monitoring time of 30 s, owing to the strongly binding of Cu2S and Au2S by hard-soft-acid-base theory and the destruction of the aggregated structure of PVP/MBT-Au@CuNCs. Furthermore, the platform also provided the portable analysis for visual detection of S2- by capturing the change in fluorescence color with a single dual-emissive ratiometric paper strip. It is worth mentioning that the fluorescent gold-copper nanoclusters showed excellent application activities in the selective detection of S2- in Radix Codonopsis or Tremella samples and recognition of S2- in HeLa cells or macrophages by confocal microscopy fluorescent imaging. Overall, the sensing system paved a new avenue for effectively developing a convenient ratiometric fluorescent sensor platform for evaluating the safety of food with S2- pollution in environment and biological system.

Plasma Homocysteine as a Potential Marker of Early Renal Function Decline in IgA Nephropathy.

Hyperhomocysteinemia (HHcy) is very common among patients with chronic kidney disease (CKD), and related to the risk of cardiovascular events and mortality in these patients. However, the prevalence of HHcy in primary causes of CKD and its role in kidney disease progression are not well-understood. In this study, we investigated the prevalence of HHcy in different CKD stages in 221 patients with IgA nephropathy (IgAN) and 194 patients with other primary glomerular diseases. We also evaluated the association of homocysteine (Hcy) [after adjusted for estimated glomerular filtration rate (eGFR)] with CKD progression event, defined as ESKD or 50% decline in eGFR, in a cohort of 365 patients with IgAN. The prevalence of HHcy was 67.9% (150/221), 53.5% (76/142), 51.5% (17/33), and 42.1% (8/19) in patients with IgAN, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, respectively. The Hcy/eGFR ratio was significantly associated with pathologic features of IgAN, including the proportion of global glomerulosclerosis (r = 0.38, p < 0.001), the proportion of ischemia originated glomerular sclerosis (r = 0.32, p < 0.001), and the severity of tubular atrophy/interstitial fibrosis (r = 0.57, p < 0.001). Importantly, Hcy/eGFR ratio was an independent risk factor for CKD progression event (hazard ratio, 1.38; 95% confidence interval, 1.13-1.68; p = 0.002). The risk of CKD progression events continuously increased with the Hcy/eGFR ratio, but reached a plateau when Hcy/eGFR ratio was >1.79. Our findings suggest that elevated Hcy/eGFR ratio may be an early marker of poor renal outcome in IgAN.

ADTKD-UMOD in a girl with a de novo mutation: A case report.

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). An autosomal dominant inheritance is the general rule, but de novo UMOD mutations have been reported. It was reported that the median age of ESKD was 47 years (18-87 years) and men were at a much higher risk of progression to ESKD. Here, we reported a 13-year-old young girl with unexplained chronic kidney disease (CKD) (elevated serum creatine) and no positive family history. Non-specific clinical and histological manifestations and the absence of evidence for kidney disease of other etiology raised strong suspicion for ADTKD. Trio whole-exome sequencing confirmed that she carried a de novo heterozygous mutation c.280T > C (p.Cys94Arg) in the UMOD gene. The functional significance of the novel mutation was supported by a structural biology approach. With no targeted therapy, she was treated as CKD and followed up regularly. The case underscores the clinical importance of a gene-based unifying terminology help to identify under-recognized causes of CKD, and it demonstrates the value of whole-exome sequencing in unsolved CKD.

Vasopressin augments TNBS-induced colitis through enteric neuronal V1a receptor-mediated COX-2-dependent prostaglandin release from mast cells in mice.

BACKGROUND: Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway. METHODS: Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V1a receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg8 )-Vasopressin (AVP)-evoked short-circuit current (Isc) was recorded in the presence of conivaptan (V1a and V2 receptor antagonist), tolvaptan (V1b receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX-1 antagonist; NS560, COX-2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively. KEY RESULTS: TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS-induced colitis, which was attenuated by conivaptan but not tolvaptan. V1a receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8-15 µA/cm2 , 10-11 mHz, and 1.5 minutes, respectively. Notably, the AVP-evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively. CONCLUSIONS AND INFERENCES: VP-V1a receptor played the proinflammatory role in TNBS-induced colitis by promoting COX-2-dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.