Modulating Electron Transfer between Pt and MOF Support through Pd Doping Promotes Nanozyme Catalytic Efficiency.

Electron transfer is considered to be a typical parameter that affects the catalytic activity of nanozymes. However, there is still controversy regarding whether higher or lower electron transfer numbers are beneficial for improving the catalytic activity of nanozymes. To address this issue, we propose the introduction of Pd doping as an important electron regulation strategy to tune electron transfer between Pt and ZIF-8 carriers (PtxPd1@ZIF-8). We observe a volcano-shaped relationship between the electron transfer number and catalytic activity, reaching its peak at Pt4Pd1@ZIF-8. Mechanism studies indicate that as the electron transfer number from Pt to ZIF-8 carriers increases, the d-band center of the active site Pt increases, reducing the occupancy of antibonding states and enhancing the adsorption capacity of the key intermediate (*O). However, a further increase in the adsorption of *O energy makes it difficult to desorb and participate in the next reaction, thus exhibiting volcanic activity. The optimized Pt4Pd1@ZIF-8 nanozyme is applied to develop an immunoassay for the detection of zearalenone, achieving a detection limit of 0.01 µg/L, which is 6 times higher than that of the traditional enzyme-linked immunosorbent assay. This work not only reveals the potential regulatory mechanism of electron transfer on the catalytic activity of nanozymes but also improves the performance of nanozyme-based biosensors.

Bioenzyme-nanoenzyme-chromogen all-in-one test strip for convenient and sensitive detection of malathion in water environment.

The presence of pesticide residues in aquatic environments poses a significant threat to both aquatic ecosystems and human health. The presence of these residues can result in significant harm to aquatic ecosystems and can negatively impact the health of aquatic organisms. Consequently, this issue requires urgent attention and effective measures to mitigate its impact. However, developing sensitive and rapid detection methods remains a challenge. In this study, an all-in-one test strip, which integrated bioenzymes, nanoenzymes, and a chromogen, was developed in combination with an enzyme labeling instrument for a highly sensitive and convenient sensing of malathion residues. The oxidase activity of heme chloride (Hemin) in the strip can catalyze the oxidation of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue-colored oxide. Simultaneously, the alkaline phosphatase (ALP) present in the strip can break down l-ascorbic acid-2-phosphate to produce ascorbic acid (AA). This AA then acts to reduce the oxidized form of TMB, turning it into a colorless substance and leading to the disappearance of its fluorescent signal. In the presence of a pesticide, the activity of ALP is inhibited and formation of AA is blocked, thereby preventing the reduction of oxidized TMB and producing a colored signal. According to this principle, the integrated test strip detected the target pesticide with high performance as per the optical density value determined via an enzyme marker. The detection limit of the test strip was 0.209 ng/mL with good sensitivity. The method was used for detecting malathion in actual river water samples, and the recoveries were in the range of 93.53 %-96.87 %. The newly devised technique effectively identified malathion in samples of natural water. This research has introduced a novel approach for the precise and convenient surveillance of pesticide remnants. Additionally, these discoveries could inspire the advancement of proficient multi-enzyme detection systems.

Investigation of clinical significance of ST-segment depression during paroxysmal supraventricular tachycardia.

INTRODUCTION: There are great differences in ST-segment depression during PSVT episodes. The aim of this study is to investigate the clinical significance of ST segment depression during PSVT. METHODS: The study enrolled 333 consecutive patients who were diagnosed with PSVT by electrophysiological test from Jan 1, 2021 to July 31, 2022. The range, magnitude and morphology of ST-segment depression were described. The correlation between ST-segment depression and symptoms of chest tightness, chest pain or hypotension, the correlation between ST-segment depression and coronary stenosis, and the possible influencing factors were analyzed. In addition, the diagnostic efficacy of ST-segment depression for AVRT was determined. RESULTS: ST-segment depression was present in 85% of patients, in 70% of which the depression range was more than six leads. The magnitude of the depression was more significant in precordial leads (P < 0.001). ST-segment depression of >1 mm in limb leads and precordial leads was found in 36.0% and 49.8% of the patients, respectively, while >3 mm was found in 2.4% and 9.6%, respectively. The morphology of ST-segment depression in limb leads was different from that in precordial leads (P < 0.001). Downsloping ST-segment depression was more common in limb leads (limb vs. precordial: 40.5% vs. 12.6%), whereas upsloping depression was more common in precordial leads (limb vs. precordial: 3.0% vs. 23.1%). Correlation analysis showed that ST-segment depression was not correlated with symptoms of chest tightness and pain, nor was it correlated with coronary artery stenosis. The most important influencing factor is the type of PSVT, especially affecting the morphology of depression in limb leads (OR = 10.27 [5.93-17.79], P < 0.001). The sensitivity and specificity of downsloping ST-segment depression in limb leads for diagnosis of AVRT were 75.5% and 76.7%. CONCLUSION: ST-segment depression is a common ECG change during PSVT episodes, and it's not associated with severe coronary stenosis. The type of PSVT has a significant effect on the manifestation of ST-segment depression. The downslope morphology of ST-segment depression in limb leads is helpful in differentiating AVRT from AVNRT.

Phenothiazine Derivatives as Small-Molecule Organic Cathodes with Adjustable Dropout Voltage and Cycle Performance.

Compared with conventional inorganic materials, organic electrodes are competitive candidates for secondary battery cathodes due to their resourcefulness, environmental friendliness, and cost-effectiveness. Much effort is devoted at the level of chemical structure, while ignoring the impact of molecular aggregation on battery behavior. Herein, this work designs a series of organic molecules with two electrochemically active phenothiazine groups linked by different lengths of alkyl chain to regulate molecular symmetry and crystallinity. The results emphasize the equally important role of molecular aggregation and chemical structure for battery performance. Among them, 2PTZ-C7 H14 |Li cell exhibits the most impressive cycle and rate performance. At the high rate of 50 C, it can still deliver a capacity of 63.4 mA h g-1 and 74.5% capacity retention after 10 000 cycles. Besides, the dropout voltage of 2PTZ-C9 H18 |Li cell is only 52 mV, which is among the lowest reported for lithium-organic batteries to the best of the author's knowledge.

The effectiveness and safety of temporary transvenous cardiac pacing leads placement into coronary sinus vein in patients with sick sinus syndrome.

BACKGROUND: The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. OBJECTIVE: We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). METHODS: We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X-ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first-attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. RESULTS: Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first-attempt success rate of lead placement was obviously increased in CSV group (both p < .05). Compared with that in RV group, the rate of leads displacement is lower in CSV group (both p < .05). There were three patients occurred cardiac perforation in RV group, but no cardiac perforation was reported in CSV group (p > .05). CONCLUSION: TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.

eDOTS: Improving the Treatment of Pulmonary Tuberculosis in Xinjiang, China.

Purpose: To increase pulmonary tuberculosis (PTB) treatment adherence in Xinjiang Region, an electronic DOTS (eDOTS) system developed was applied and evaluated. Methods: An eDOTS system comprised electronic medicine boxes, mobile phones and a central processing platform. Between April and June 2016, persons with active PTB (PAPTB) were recruited from villages and a city and were prescribed a six-month course of antibiotics using either DOTS or eDOTS. Treatment adherence rate and chest X-ray digital radiography (DR) score were used to evaluate usefulness of eDOTS. Results: A total 167 PAPTB were recruited with 81 participants from villages and 86 from neighbourhoods. Of the 81 village patients, 43 (53%) used eDOTS and 38 (47%) used DOTS. Among the 86 patients from neighbourhoods, 50 (58%) used eDOTS and 36 (42%) used DOTS. After 6 months of treatment, the average treatment compliance of the village patients who used eDOTS were 47.0%±20.5% compared to 26.7%±21.1% who used DOTS (t=-4.475, p<0.001). The patients using eDOTS from both the villages and city had significantly lower X-ray DR scores than the patients using DOTS by 1.81 points, 95% CI (0.72-2.90) and 1.05 points, 95% CI (0.15-1.95), respectively. Conclusion: eDOTS is an effective means of managing the treatment of active PTB patients through daily reminding and monitoring of patient compliance. Ease of contact with doctors and special education programs encouraged PAPTB to complete their treatment course as required.

The signaling pathway of hypoxia inducible factor in regulating gut homeostasis.

Hypoxia represent a condition in which an adequate amount of oxygen supply is missing in the body, and it could be caused by a variety of diseases, including gastrointestinal disorders. This review is focused on the role of hypoxia in the maintenance of the gut homeostasis and related treatment of gastrointestinal disorders. The effects of hypoxia on the gut microbiome and its role on the intestinal barrier functionality are also covered, together with the potential role of hypoxia in the development of gastrointestinal disorders, including inflammatory bowel disease and irritable bowel syndrome. Finally, we discussed the potential of hypoxia-targeted interventions as a novel therapeutic approach for gastrointestinal disorders. In this review, we highlighted the importance of hypoxia in the maintenance of the gut homeostasis and the potential implications for the treatment of gastrointestinal disorders.

Intensive Lipid-Lowering Therapy as per the Latest Dyslipidemia Management Guideline in Predicting Favorable Long-Term Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Grafting: A Retrospective Cohort Study.

Background There are limited data on low-density lipoprotein cholesterol (LDL-C) goal achievement per the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia management guidelines and its impact on long-term outcomes in patients undergoing coronary artery bypass grafting (CABG). We investigated the association between LDL-C levels attained 1 year after CABG and the long-term outcomes. Methods and Results A total of 2072 patients diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were included. Patients were categorized by lipid levels at 1 year after CABG, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was evaluated. The goal of LDL-C <1.40 mmol/L was attained in only 310 patients (14.9%). During a mean follow-up of 4.2 years after the index 1-year assessment, 25.0% of the patients experienced MACCEs. Multivariable-adjusted hazard ratios (95% CIs) for MACCEs, cardiac death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and cardiac rehospitalization were 1.94 (1.41-2.67), 2.27 (1.29-3.99), 2.45 (1.55-3.88), 1.17 (0.63-2.21), 2.47 (1.31-4.66), and 1.87 (1.19-2.95), respectively, in patients with LDL-C ≥2.60 mmol/L, compared with patients with LDL-C <1.40 mmol/L. The LDL-C levels at 1-year post-CABG were independently associated with long-term MACCEs. Conclusions This retrospective analysis demonstrates that lipid goals are not attained in the vast majority of patients at 1 year after CABG, which is independently associated with the increased risk of long-term MACCEs. Further prospective, multicenter studies are warranted to validate if intensive lipid management could improve the outcomes of patients undergoing CABG.

Dapagliflozin impedes endothelial cell senescence by activating the SIRT1 signaling pathway in type 2 diabetes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA-ß-gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.

Cationic N,S-chelate half-sandwich iridium complexes: synthesis, characterization, anticancer and antiplasmodial activity.

A series of pyrazole-based ligands and their corresponding cationic N,S-chelate half-sandwich iridium complexes were successfully synthesized. All iridium complexes exhibited good anticancer activity against the MCF-7 and MDA-MB-231 human breast cancer cells. The cytotoxic activity of unsubstituted iridium complex 1 is greater than that of cisplatin against MCF-7 cells. In addition, the cationic half-sandwich iridium complexes are also efficient in antiplasmodial study and complex 1 displayed the best activity as its IC50 was observed to be approximately 0.11 µM against the CQS-NF54 strain. These iridium complexes generally exhibited enhanced activity against the CQS-NF54 strain in comparison with that against the CQR-K1 strain. An "IC50 speed assay" investigation against the CQS-NF54 strain indicated complexes 1-3 to be fast-acting complexes that reach their lowest IC50 values within 16 hours. All complexes were fully characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis, and the structure of the iridium complex was confirmed by single-crystal X-ray diffraction.

Half-sandwich iridium complexes with hydrazone ligands: preparation, structure, and catalytic synthesis of cyanosilylethers under air.

A series of hydrazone-based N,O-chelate half-sandwich iridium complexes were synthesized through a facile route with good yields. These air- and moisture-stable iridium complexes exhibited excellent catalytic activity in the cyanosilylether synthesis under mild reaction conditions. Under the catalysis of iridium, various cyanosilylethers with different substituents were obtained through a one-pot reaction of trimethylsilyl cyanide (TMSCN) with carbonyl substrates, with good to excellent yields. The excellent catalytic efficiency, wide substrate range, and mild reaction conditions made this type of iridium catalyst have the potential for industrial applications. All the half-sandwich iridium complexes were well characterized by IR, NMR, and EA analyses. The molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.

The neuromodulatory effects of flavonoids and gut Microbiota through the gut-brain axis.

Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.

The prognostic and biology of tumour-infiltrating lymphocytes in the immunotherapy of cancer.

Tumour immunotherapy has achieved remarkable clinical success in many different types of cancer in the past two decades. The outcome of immune checkpoint inhibitors in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell within the tumour microenvironment, suggesting that the immune landscape of a tumour is highly connected to patient response and prognosis. It is critical to understanding tumour immune microenvironments for identifying immune modifiers of cancer progression and developing cancer immunotherapies. The infiltration of solid tumours by immune cells with anti-tumour activity is both a strong prognostic factor and a therapeutic goal. Recent approaches and applications of new technologies, especially single-cell mRNA analysis in dissecting tumour microenvironments have brought important insights into the biology of tumour-infiltrating immune cells, revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune response. In this review, we will discuss recent advances in the understanding of tumour infiltrated lymphocytes, their prognostic benefit, and predictive value for immunotherapy.

Beyond cellulose: pharmaceutical potential for bioactive plant polysaccharides in treating disease and gut dysbiosis.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

A novel glycyrrhizin acid-coated stent reduces neointimal formation in a rabbit iliac artery model.

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent. Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups. Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model. Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization.

Half-Sandwich Ruthenium Complexes with Hydrazone Ligands: Preparation, Structure, and Catalytic Activity in Cyanosilylether Synthesis under an Air Atmosphere.

A new class of N,O-coordinate half-sandwich ruthenium complexes supported by hydrazone ligands with a general formula of [Ru(η6-p-cymene)Cl(L)] have been obtained in moderate to excellent yields conveniently. These air- and moisture-stable ruthenium complexes exhibited excellent catalytic activity in cyanosilylether synthesis under mild reaction conditions. Under the catalysis of ruthenium, various cyanosilylethers with different substituents were obtained through a one-pot reaction of trimethylsilyl cyanide with carbonyl substrates, with good to excellent yields. Excellent catalytic efficiency, a wide substrate range, and mild reaction conditions made this type of ruthenium catalyst have potential for industrial application. All of the half-sandwich ruthenium complexes have been well described by infrared, nuclear magnetic resonance, and EA analysis. Molecular structures of ruthenium complexes 1 and 4 were confirmed by single-crystal X-ray analysis.

Ultralong Room-Temperature Phosphorescence with Second-level Lifetime in Water Based on Cyclodextrin Supramolecular Assembly.

Organic solid-state materials with long-lived room-temperature phosphorescence (RTP) emission have been widely developed and applied in many fields, while works in developing solution-phase phosphorescence materials were rarely reported owing to the ultrafast nonradiative relaxation and quenchers from the liquid medium. Herein, we report an ultralong RTP system in water through assembly based on a ß-cyclodextrin host and p-biphenylboronic acid guest with a lifetime of 1.03 s under ambient conditions. It is worth noting that the long-lived phosphorescence depends on the host-guest inclusion as well as intermolecular hydrogen bonding interactions, which suppress nonradiative relaxation and avoid quenchers effectively. Furthermore, the addition of fluorescent dyes to the assembly system achieved the tuning of the afterglow color through radiative energy transfer of reabsorption.

A bibliometric analysis of hotpots and trends for the relationship between skin inflammation and regeneration.

Background: Skin regeneration is a challenging issue worldwide. Increasing research has highlighted the role of immune cells in healing and the underlying regulatory mechanism. The purpose of this study was to identify the hotspots and trends in skin regeneration and inflammation research through bibliometrics and to provide insights into the future development of fundamental research and disease treatment. Methods: Publications were collected from the Web of Science Core Collection on March 1, 2022. Articles and reviews published in English from January 1, 1999, to December 31, 2022, were selected, and statistical analyses of countries, institutions, authors, references, and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8. Results: A total of 3,894 articles and reviews were selected. The number of publications on skin inflammation and regeneration showed an increasing trend over time. Additionally, authors and institutions in the United States, United Kingdom, Canada, and China appeared to be at the forefront of research in the field of skin inflammation and regeneration. Werner Sabine published some of the most cited papers. Wound Repair and Regeneration was the most productive journal, while Journal of Investigative Dermatology was the most cited journal. Angiogenesis, diamonds, collagen, cytokine, and keratinocytes were the five most commonly used keywords. Conclusion: The number of publications on skin inflammation and regeneration show an increasing trend. Moreover, a series of advanced technologies and treatments for skin regeneration, such as exosomes, hydrogels, and wound dressings, are emerging, which will provide precise information for the treatment of skin wounds. This study can enhance our understanding of current hotspots and future trends in skin inflammation and regeneration research, as well as provide guidelines for fundamental research and clinical treatment.

High Antioxidant Capacity of Lacticaseibacillus paracasei TDM-2 and Pediococcus pentosaceus TCM-3 from Qinghai Tibetan Plateau and Their Function towards Gut Modulation.

Probiotic supplementation is a key therapeutic strategy for promoting gut health and maintaining gut homeostasis by modulating functional microbiota. In this study, we isolated two lactic acid bacteria (LAB) strains, Pediococcus pentosaceus TCM-3 and Lacticaseibacillus paracasei TDM-2, from Qinghai-Tibetan plateau, and evaluated their probiotic properties and antioxidant bioactivity. In which, TDM-2 had higher T-AOC activity than either TCM-3 or LGG (4.10 µmol/mL vs. 3.68 and 3.53 µmol/mL, respectively, p < 0.05). These strains have shown high antioxidant activity compared to the LAB strains and were found to be acid and bile salt tolerant, confronting the safety issues of antibiotic resistance and the capability of surviving in simulated gastric and intestinal juices. In vitro fermentation experiments with human gut microbiota revealed significant differences in microbial community composition between samples supplemented with TCM-3 and TDM-2 and those without. The addition of these two strains resulted in an enrichment of beneficial taxa, such as the Pediococcus, Lactobacillus, and Clostridium_sensu_strictos at the genus level, and Firmicutes and Proteobacteria at the phylum level. Notably, the TCM-3 group exhibited higher short-chain fatty acid production than the TDM-2 group and untreated controls (acetic acid at 12 h: 4.54 mmol L-1 vs. 4.06 mmol L-1 and 4.00 mmol L-1; acetic acid at 24 h: 4.99 mmol L-1 vs. 4.90 mmol L-1 and 4.82 mmol L-1, p < 0.05). These findings demonstrate that LAB supplementation with high antioxidant capacity and probiotic properties can promote gut health by modulating functional microbiota and is enriching for beneficial taxa. Our study provides guidance for therapeutic strategies that use novel LAB strains to maintain gut homeostasis and functional microbiota modulation.

A new neurodevelopmental disorder linked to heterozygous variants in UNC79.

PURPOSE: The "NALCN channelosome" is an ion channel complex that consists of multiple proteins, including NALCN, UNC79, UNC80, and FAM155A. Only a small number of individuals with a neurodevelopmental syndrome have been reported with disease causing variants in NALCN and UNC80. However, no pathogenic UNC79 variants have been reported, and in vivo function of UNC79 in humans is largely unknown. METHODS: We used international gene-matching efforts to identify patients harboring ultrarare heterozygous loss-of-function UNC79 variants and no other putative responsible genes. We used genetic manipulations in Drosophila and mice to test potential causal relationships between UNC79 variants and the pathology. RESULTS: We found 6 unrelated and affected patients with UNC79 variants. Five patients presented with overlapping neurodevelopmental features, including mild to moderate intellectual disability and a mild developmental delay, whereas a single patient reportedly had normal cognitive and motor development but was diagnosed with epilepsy and autistic features. All displayed behavioral issues and 4 patients had epilepsy. Drosophila with UNC79 knocked down displayed induced seizure-like phenotype. Mice with a heterozygous loss-of-function variant have a developmental delay in body weight compared with wild type. In addition, they have impaired ability in learning and memory. CONCLUSION: Our results demonstrate that heterozygous loss-of-function UNC79 variants are associated with neurologic pathologies.