A 3-year follow-up analysis of renal function in elderly patients with type 2 diabetes mellitus and an estimated glomerular filtration rate <90 mL/min/1.73m2: A retrospective cohort study.

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Programmed alternating current optimization of Cu-catalyzed C-H bond transformations.

Direct current (DC) electrosynthesis, which has undergone optimization over the past century, plays a pivotal role in a variety of industrial processes. Alternating current (AC) electrosynthesis, characterized by polarity reversal and periodic fluctuations, may be advantageous for multiple chemical reactions, but apparatus, principles, and application scenarios remain underdeveloped. In this work, we introduce a protocol for programmed AC (pAC) electrosynthesis that systematically adjusts currents, frequencies, and duty ratios. The application of representative pAC waveforms facilitates copper-catalyzed carbon-hydrogen bond cleavage in cross-coupling and difunctionalization reactions that exhibit suboptimal performance under DC and chemical oxidation conditions. Moreover, observing catalyst dynamic variation under diverse waveform applications provides mechanistic insight.

Nerve conduction features may serve as a diagnostic clue for neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease is a neurodegenerative disorder with a wide phenotypic spectrum, including peripheral neuropathy. This study aims to characterize the nerve conduction features and proposes an electrophysiological criterion to assist the diagnosis of neuronal intranuclear inclusion disease. In this study, nerve conduction studies were performed in 50 genetically confirmed neuronal intranuclear inclusion disease patients, 200 age- and sex-matched healthy controls and 40 patients with genetically unsolved leukoencephalopathy. Abnormal electrophysiological parameters were defined as mean values plus or minus two standardized deviations of the healthy controls or failure to evoke a response on the examined nerves. Compared to controls, neuronal intranuclear inclusion disease patients had significantly slower motor and sensory nerve conduction velocities, as well as lower amplitudes of compound motor action potentials and sensory nerve action potentials in all tested nerves (P < 0.05). Forty-eight of the 50 neuronal intranuclear inclusion disease patients (96%) had at least one abnormal electrophysiological parameter, with slowing of motor nerve conduction velocities being the most prevalent characteristic. The motor nerve conduction velocities of median, ulnar, peroneal and tibial nerves were 44.2 ± 5.5, 45.3 ± 6.1, 37.3 ± 5.3 and 35.6 ± 5.1 m/s, respectively, which were 12.4-13.6 m/s slower than those of the controls. The electrophysiological features were similar between neuronal intranuclear inclusion disease patients manifesting with CNS symptoms and those with PNS-predominant presentations. Thirteen of the 14 patients (93%) who underwent nerve conduction study within the first year of symptom onset exhibited abnormal findings, indicating that clinical or subclinical peripheral neuropathy is an early disease marker of neuronal intranuclear inclusion disease. We then assessed the feasibility of using motor nerve conduction velocity as a diagnostic tool of neuronal intranuclear inclusion disease and evaluated the diagnostic performance of various combinations of nerve conduction parameters using receiver operating characteristic curve analysis. The criterion of having at least two nerves with motor nerve conduction velocity ranging from 35 to 50 m/s in median/ulnar nerves and 30-40 m/s in tibial/peroneal nerves demonstrated high sensitivity (90%) and specificity (99%), with an area under the curve of 0.95, to distinguish neuronal intranuclear inclusion disease patients from healthy controls. The criterion's diagnostic performance was validated on an independent cohort of 56 literature reported neuronal intranuclear inclusion disease cases (area under the curve = 0.93, sensitivity = 87.5%, specificity = 99.0%), and in distinguishing neuronal intranuclear inclusion disease from genetically unresolved leukoencephalopathy cases (sensitivity = 90.0%, specificity = 80.0%). In conclusion, mildly to moderately decreased motor nerve conduction velocity in multiple nerves is a significant electrophysiological hallmark assisting the diagnosis of neuronal intranuclear inclusion disease, regardless of CNS- or PNS-predominant manifestations.

Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis.

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

G protein subunit Gγ13-mediated signaling pathway is critical to the inflammation resolution and functional recovery of severely injured lungs.

Tuft cells are a group of rare epithelial cells that can detect pathogenic microbes and parasites. Many of these cells express signaling proteins initially found in taste buds. It is, however, not well understood how these taste signaling proteins contribute to the response to the invading pathogens or to the recovery of injured tissues. In this study, we conditionally nullified the signaling G protein subunit Gγ13 and found that the number of ectopic tuft cells in the injured lung was reduced following the infection of the influenza virus H1N1. Furthermore, the infected mutant mice exhibited significantly larger areas of lung injury, increased macrophage infiltration, severer pulmonary epithelial leakage, augmented pyroptosis and cell death, greater bodyweight loss, slower recovery, worsened fibrosis and increased fatality. Our data demonstrate that the Gγ13-mediated signal transduction pathway is critical to tuft cells-mediated inflammation resolution and functional repair of the damaged lungs.To our best knowledge, it is the first report indicating subtype-specific contributions of tuft cells to the resolution and recovery.

Electrochemical Decarboxylative Cross-Coupling with Nucleophiles.

Decarboxylative cross-coupling reactions are powerful tools for carbon-heteroatom bonds formation, but typically require pre-activated carboxylic acids as substrates or heteroelectrophiles as functional groups. Herein, we present an electrochemical decarboxylative cross-coupling of carboxylic acids with structurally diverse fluorine, alcohol, H2O, acid, and amine as nucleophiles. This strategy takes advantage of the ready availability of these building blocks from commercial libraries, as well as the mild and oxidant-free conditions provided by electrochemical system. This reaction demonstrates good functional-group tolerance and its utility in late-stage functionalization.

A Peritrophin-44 gene in Litopenaeus vannamei is involved in disease resistance.

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance.

A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

Electrochemical Oxidation Enables Radical Dearomative Spiroannulation to 2H-Spiro[benzofuran-3,9'-fluoren]-2-one.

Developing pragmatic strategies for accessing functional benzofuran-2-ones from 3-([1,1'-biphenyl]-2-yl)benzofuran remains an enduring challenge. Herein, we have achieved a highly discriminating electrochemical oxidative dearomative spiroannulation of 3-([1,1'-biphenyl]-2-yl)benzofuran, culminating in the synthesis of 2H-spiro[benzofuran-3,9'-fluoren]-2-one derivatives. By harnessing the electrophilic intermediates of benzofuryl radical cations supported by DFT calculations, we attain exceptional regioselectivity while eliminating the need for stoichiometric oxidants. Mechanistic investigations reveal a sequence of events involving the benzofuran radical cation, encompassing the capture of H2O, nucleophilic arene attack, and subsequent deprotonation, ultimately yielding the final benzofuran-2-ones.

Hierarchical porous amorphous metal-organic frameworks constructed from ZnO/MOF glass composites.

For the first time, hierarchical porous amorphous metal-organic frameworks (HP-aMOFs) containing ultramicropores, micropores, and mesopores were synthesized by etching a composite of MOF glass (agZIF-76) and ZnO using ammonia. These materials show potential applications in the adsorption of C2 hydrocarbons.

Tumor budding is an optimal indictor of occult cervical metastasis in clinical early-stage buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC. METHODS: Seventy-one cT1-2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively. RESULTS: Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94-116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS. CONCLUSIONS: The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.

Bilateral Production Shield Enabling Highly Efficient Perovskite Photovoltaics.

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Nonlinear associations between the ratio of family income to poverty and all-cause mortality among adults in NHANES study.

Socioeconomic status (SES) has been linked to mortality rates, with family income being a quantifiable marker of SES. However, the precise association between the family income-to-poverty ratio (PIR) and all-cause mortality in adults aged 40 and older remains unclear. A cross-sectional study was conducted using data from NHANES III, including 20,497 individuals. The PIR was used to assess financial status, and various demographic, lifestyle, and clinical factors were considered. Mortality data were collected from the NHANES III linked mortality file. The study revealed a non-linear association between PIR and all-cause mortality. The piecewise Cox proportional hazards regression model showed an inflection point at PIR 3.5. Below this threshold, the hazard ratio (HR) for all-cause mortality was 0.85 (95% CI 0.79-0.91), while above 3.5, the HR decreased to 0.66 (95% CI 0.57-0.76). Participants with lower income had a higher probability of all-cause mortality, with middle-income and high-income groups showing lower multivariate-adjusted HRs compared to the low-income group. This study provides evidence of a non-linear association between PIR and all-cause mortality in adults aged 40 and older, with an inflection point at PIR 3.5. These findings emphasize the importance of considering the non-linear relationship between family income and mortality when addressing socioeconomic health disparities.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.