Enhancing Li-S Battery Performance with Limiting Li[N(SO2F)2] Content in a Sulfolane-Based Sparingly Solvating Electrolyte.

By enhancing the stability of the lithium metal anode and mitigating the formation of lithium dendrites through electrolyte design, it becomes feasible to extend the lifespan of lithium-sulfur (Li-S) batteries. One widely accepted approach involves the utilization of Li[N(SO2F)2] (Li[FSA]), which holds promise in stabilizing the lithium anode by facilitating the formation of an inorganic-dominant solid electrolyte interface (SEI) film. However, the use of Li[FSA] encounters limitations due to inevitable side reactions between lithium polysulfides (LiPSs) and [FSA] anions. In this study, our focus lies in precisely controlling the composition of the SEI film and the morphology of the deposited lithium, as these two critical factors profoundly influence lithium reversibility. Specifically, by subjecting an initial charging process to an elevated temperature, we have achieved a significant enhancement in lithium reversibility. This improvement is accomplished through the employment of a LiPS sparingly solvating electrolyte with a restricted Li[FSA] content. Notably, these optimized conditions have resulted in an enhanced cycling performance in practical Li-S pouch cells. Our findings underscore the potential for improving the cycling performance of Li-S batteries, even when confronted with challenging constraints in electrolyte design.

Clinical and genetic features of cystic fibrosis in Japan.

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.

Semaglutide is effective in type 2 diabetes and obesity with schizophrenia.

Background: Prevention and treatment of type 2 diabetes and obesity are problematic for individuals with schizophrenia partly because atypical antipsychotics and mental distress themselves increase appetite, thus promoting subsequent body weight gain and deterioration of glycemic control. Glucagon-like peptide-1 (GLP-1) receptor agonists have been gaining attention for their glucose-lowering and body weight-reducing effects in obese individuals with type 2 diabetes generally, but their effects in those also having schizophrenia have not been adequately addressed. Case presentation: This case was a 50-year-old obese woman having type 2 diabetes and schizophrenia. Although she was receiving oral anti-diabetes treatment, her HbA1c remained inadequately controlled (8.0-9.0%) partly due her difficulty in following instructions on heathy diet and exercise. In addition, she was repeatedly hospitalized due to suicide attempts by overdosing on her anti-psychotic and anti-diabetes drugs. Her HbA1c was elevated to as high as 10.2% despite the use of multiple anti-diabetes drugs including the GLP-1 receptor agonist dulaglutide, and she was hospitalized in our department. We chose the GLP-1 receptor agonist semaglutide to replace dulaglutide along with a multidisciplinary team approach that included a cognitive-behavioral therapist. The patient perceived that her hunger was suppressed when she started receiving semaglutide 0.5 mg. After discharge, semaglutide was remarkably more effective than dulaglutide in that it reduced and maintained the patient's HbA1c and body weight for 6 months after initiation of the drug. Conclusion: The GLP-1 receptor agonist semaglutide can be effective in maintaining appropriate control of glycemia and body weight in diabetes and obesity with schizophrenia.

Bicarbonate transport of airway surface epithelia in luminally perfused mice bronchioles.

HCO3- secretion in distal airways is critical for airway mucosal defense. HCO3-/H+ transport across the apical membrane of airway surface epithelial cells was studied by measuring intracellular pH in luminally microperfused freshly dissected mice bronchioles. Functional studies demonstrated that CFTR, ENaC, Cl--HCO3- exchange, Na+-H+ exchange, and Na+-HCO3- cotransport are involved in apical HCO3-/H+ transport. RT-PCR of isolated bronchioles detected fragments from Cftr, α, ß, γ subunits of ENaC, Ae2, Ae3, NBCe1, NBCe2, NBCn1, NDCBE, NBCn2, Nhe1, Nhe2, Nhe4, Nhe5, Slc26a4, Slc26a6, and Slc26a9. We assume that continuous decline of intracellular pH following alkaline load demonstrates time course of HCO3- secretion into the lumen which is perfused with a HCO3--free solution. Forskolin-stimulated HCO3- secretion was substantially inhibited by luminal application of CFTRinh-172 (5 µM), H2DIDS (200 µM), and amiloride (1 µM). In bronchioles from a cystic fibrosis mouse model, basal and acetylcholine-stimulated HCO3- secretion was substantially impaired, but forskolin transiently accelerated HCO3- secretion of which the magnitude was comparable to wild-type bronchioles. In conclusion, we have characterized apical HCO3-/H+ transport in native bronchioles. We have demonstrated that cAMP-mediated and Ca2+-mediated pathways are involved in HCO3- secretion and that apical HCO3- secretion is largely mediated by CFTR and H2DIDS-sensitive Cl--HCO3- exchanger, most likely Slc26a9. The impairment of HCO3- secretion in bronchioles from a cystic fibrosis mouse model may be related to the pathogenesis of early lung disease in cystic fibrosis.

Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report.

Glucokinase has an important role in regulating glycolysis as a glucose sensor in liver and pancreatic ß cells. Glucokinase-maturity onset diabetes in young (GCK-MODY also known as MODY2) is caused by autosomal dominant gene mutation of the GCK gene; it is characterized by mild fasting hyperglycemia and small 2-h glucose increment during 75 g-oral glucose tolerance test (OGTT) as well as near-normal postprandial glucose variabilities. A 10-year-old girl with family history of diabetes visited her physician after being found positive for urinary glucose by school medical checkup. She received a diagnosis of diabetes based on the laboratory data: 75 g-OGTT (mild fasting hyperglycemia and small 2-h glucose increment) and factory-calibrated glucose monitoring (mild elevation of average glucose level and near-normal glycemic variability), which raised suspicion of GCK-MODY. She was then referred to our institution for genetic examination, which revealed a GCK heterozygous mutation (NM_000162: exon10: c.1324G>T: p.E442X) in the proband as well as in her mother and maternal grandmother, who had been receiving anti-diabetes medications without knowing that they had GCK-MODY specifically. GCK-MODY cases show incidence of microvascular and macrovascular diseases similar to that of normal subjects, and their glucose levels are adequately controlled without anti-diabetes drug use. Thus, early and definitive diagnosis of MODY2 by genetic testing is important to avoid unnecessary medication.

Uterine cervical squamous cell carcinoma with reactive multinucleated giant cells expressing cluster of differentiation 204: A case report and literature review.

Uterine cervical squamous cell carcinoma (SCC) with reactive multinucleated giant cells (MGC) is extremely rare. Here we present the case of a 49-year-old woman treated with radical hysterectomy, bilateral adnexectomy and lymph node dissection. Histologically, the cervical tumor was diagnosed as nonkeratinizing SCC of pT1b1N0M0, with negative surgical margin. Many MGC including osteoclast-like giant cells with immunohistochemical expression of cluster of differentiation 204, a marker for the M2 macrophage, were present around the tumor nests. The patient received postoperative radiation therapy and achieved 22 months of disease-free survival after the surgery. M2 macrophages promote aggressiveness of the carcinoma and it is suggested that SCC of the cervix with reactive MGC might have poor prognosis; however, our case paradoxically showed a favorable course. From literature review of six cases, including our case, the effect of MGC-reaction may vary with respect to other factors, such as age, cancer stage or histological type.

Nociceptin/orphanin FQ reverses mecamylamine-induced learning and memory impairment as well as decrease in hippocampal acetylcholine release in the rat.

Nociceptin/orphanin FQ is an endogenous neuropeptide that plays important roles in several physiological functions including pain, anxiety, locomotion, learning, and memory. We previously reported that low doses of nociceptin improved the scopolamine-induced impairment of learning and memory in the passive avoidance test and the spontaneous Y-maze alternation task in mice. In the present study, the effects of nociceptin on learning and memory impairment as well as the decrease in acetylcholine release induced by mecamylamine were investigated in rats. Mecamylamine (49 micromol/kg, s.c.), a nicotinic acetylcholine receptor antagonist, impaired learning and memory in the step-through type passive avoidance test and decreased acetylcholine release in the hippocampus, as determined by in vivo microdialysis. The administration of nociceptin (10 fmol/rat, i.c.v.) reversed the impairment of learning and memory and blocked the decrease in acetylcholine release induced by mecamylamine. This ameliorating effect on the mecamylamine-induced impairment of learning and memory was not blocked by [NPhe(1)]nociceptin(1-13)NH(2) (1 nmol/rat, i.c.v.), an opioid receptor-like 1 (NOP) receptor antagonist. These results suggest that nociceptin improves the impairment of learning and memory as well as decrease in acetylcholine release induced by mecamylamine, and that these effects may not be mediated by NOP receptors.