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Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both EBV latency infection genes EBNA-1, LMP-1, and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in the HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and up-regulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF should be the EBV infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. Chromatin immunoprecipitation study revealed BDNF transcription could be promoted by a cooperation between EBV nuclear antigens, chromatin modifiers, and B cell specific transcription. Knockdown of BDNF in EBV infected B cells resulted in inhibition of cells proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV infected B cells into rat bladder walls resulted in higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV infected B cells in HIC pathogenesis. This article is protected by copyright. All rights reserved.

This study examined the effects of overweight/obesity on mortality and morbidity outcomes and the disparities, time trends, and projected future obesity health burden in China.Cohort studies that were conducted in China and published in English or Chinese between January 1, 1995, and July 31, 2021, were systematically searched. This study focused on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension, cardiovascular diseases, metabolic syndrome, cancers, and chronic kidney disease.A total of 31 cohorts and 50 cohort studies reporting on mortality (n = 20) and morbidities (n = 30) associated with obesity met study inclusion criteria. Overall, BMI was nonlinearly (U-shaped) associated with all-cause mortality and linearly associated with risks of T2DM, cardiovascular diseases, hypertension, cancer, metabolic syndrome, and chronic kidney disease. In 2018, among adults, the prevalence of overweight/obesity, hypertension, and T2DM was 51.2%, 27.5%, and 12.4%, respectively. Their future projected prevalence would be 70.5%, 35.4%, and 18.5% in 2030, respectively. The projected number of adults having these conditions would be 810.65 million, 416.47 million, and 217.64 million, respectively. The urban-rural disparity in overweight/obesity prevalence was projected to shrink and then reverse over time.The current health burden of obesity in China is high and it will sharply increase in coming years and affect population groups differently. China needs to implement vigorous interventions for obesity prevention and treatment.

Tacrolimus a first-line medication used after transplantation can induce β-cell dysfunction, causing new-onset diabetes mellitus (NODM). Regenerating islet-derived protein 3 gamma (Reg3g), a member of the pancreatic regenerative gene family, has been reported to improve type 1 diabetes by promoting β-cell regeneration. We aim to investigate the role of Reg3g in reversing tacrolimus-induced β-cell dysfunction and NODM in mice.Circulating REG3A (the human homologue of mouse Reg3g) in heart transplantation patients treated with tacrolimus was detected. The glucose-stimulated insulin secretion and mitochondrial functions, including mitochondria membrane potential (MMP), mitochondria calcium, ATP production, oxygen consumption rate and mitochondrial morphology were investigated in β-cells. Additionally, effects of Reg3g on tacrolimus-induced NODM in mice were analysed.Circulating REG3A level in heart transplantation patients with NODM significantly decreased compared with those without diabetes. Tacrolimus down-regulated Reg3g via inhibiting STAT3-mediated transcription activation. Moreover, Reg3g restored glucose-stimulated insulin secretion suppressed by tacrolimus in β-cells by improving mitochondrial functions, including increased MMP, mitochondria calcium uptake, ATP production, oxygen consumption rate and contributing to an intact mitochondrial morphology. Mechanistically, Reg3g increased accumulation of pSTAT3(Ser727) in mitochondria by activating ERK1/2-STAT3 signalling pathway, leading to restoration of tacrolimus-induced mitochondrial impairment. Reg3g overexpression also effectively mitigated tacrolimus-induced NODM in mice.Reg3g can significantly ameliorate tacrolimus-induced β-cell dysfunction by restoring mitochondrial function in a pSTAT3(Ser727)-dependent manner. Our observations identify a novel Reg3g-mediated mechanism that is involved in tacrolimus-induced NODM and establish the novel role of Reg3g in reversing tacrolimus-induced β-cell dysfunction.

Rechargeable lithium-metal batteries with a cell-level specific energy of >400 Wh kg-1 are highly desired for next-generation storage applications, yet the research has been retarded by poor electrolyte-electrode compatibility and rigorous safety concerns. We demonstrate that by simply formulating the composition of conventional electrolytes, a hybrid electrolyte was constructed to ensure high (electro)chemical and thermal stability with both the Li-metal anode and the nickel-rich layered oxide cathodes. By employing the new electrolyte, Li∥LiNi0.6 Co0.2 Mn0.2 O2 cells show favorable cycling and rate performance, and a 10 Ah Li∥LiNi0.8 Co0.1 Mn0.1 O2 pouch cell demonstrates a practical specific energy of >450 Wh kg-1 . Our findings shed light on reasonable design principles for electrolyte and electrode/electrolyte interfaces toward practical realization of high-energy rechargeable batteries.

This study aimed to explore the effect of performing remote health education via WeChat to improve the pre-operative nutritional status of non-restrictive ventricular septal defects (VSD).A prospective randomised controlled study was conducted in a provincial maternity and child hospital in China. Participants were randomised regarding education to the intervention group (WeChat) and the control group (leaflets). The nutritional status and complications of the patients were compared after intervening for 1 month.Nutrient status comparison at 1 month after intervention showed that the body weight, head circumference, haemoglobin, albumin and pre-albumin of the WeChat group were significantly higher than those of the leaflet group (P 0.05). The STRONGkids score of the WeChat group was significantly lower than that of the leaflet group (P 0.05). The incidence of feeding intolerance and respiratory tract infection in the WeChat group was significantly lower than that found in the leaflet group (P 0.05). There was no significant difference in the incidence of liver insufficiency and jaundice between the two groups (P 0.05).Providing pre-operative feeding and care guidance for parents of infants with non-restrictive VSD, via remote health education through WeChat, can effectively improve nutritional status and reduce the risk of malnutrition and feeding complications.

A 60‐year‐old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real‐world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor., • Neoadjuvant tislelizumab and chemotherapy was offered for a patient with Pancoast tumor (TNM stage, cT4N0M0 IIIA). • Surgical resection was successfully performed and a pCR was achieved.

As two stable hydrogen isotopes, protium and deuterium show magnified isotope effects in physicochemical properties due to the significantly varied atomic masses. In this work, aqueous electrolytes based on heavy water (D

A hybrid solid/liquid electrolyte with superior security facilitates the implementation of high-energy-density storage devices, but it suffers from inferior chemical compatibility with cathodes. Herein, an optimal lithium difluoro(oxalato)borate salt was introduced to build in situ an amorphous cathode electrolyte interphase (CEI) between Ni-rich cathodes and hybrid electrolyte. The CEI preserves the surface structure with high compatibility, leading to enhanced interfacial stability. Meanwhile, the space-charge layer can be prominently mitigated at the solid/solid interface via harmonized chemical potentials, acquiring promoted interfacial dynamics as revealed by COMSOL simulation. Consequently, the amorphous CEI integrates the bifunctionality to provide an excellent cycling stability, high Coulombic efficiency, and favorable rate capability in high-voltage Li-metal batteries, innovating the design philosophy of functional CEI strategy for future high-energy-density batteries.

Background Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin‐based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin‐induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin‐based chemotherapy. Methods In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI‐CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ‐CIPN20), time to grade 2 neurotoxicity (NCI‐CTCAE or the oxaliplatin‐specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3‐year disease‐free survival (DFS) and adverse events. Results There were no significant differences between the arms in the rate of NCI‐CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ‐CIPN20 or time to grade 2 neurotoxicity using NCI‐CTCAE and the oxaliplatin‐specific neuropathy scale. GM1 substantially decreased participant‐reported acute neurotoxicity (sensitivity to cold items [P, Neuropathy is the most prominent dose‐limiting toxicity of oxaliplatin. Patients receiving Monosialotetrahexosylganglioside (GM1) were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity.