Surface atom knockout for the active site exposure of alloy catalyst.

The fine regulation of catalysts by the atomic-level removal of inactive atoms can promote the active site exposure for performance enhancement, whereas suffering from the difficulty in controllably removing atoms using current micro/nano-scale material fabrication technologies. Here, we developed a surface atom knockout method to promote the active site exposure in an alloy catalyst. Taking Cu3Pd alloy as an example, it refers to assemble a battery using Cu3Pd and Zn as cathode and anode, the charge process of which proceeds at about 1.1 V, equal to the theoretical potential difference between Cu2+/Cu and Zn2+/Zn, suggesting the electricity-driven dissolution of Cu atoms. The precise knockout of Cu atoms is confirmed by the linear relationship between the amount of the removed Cu atoms and the battery cumulative specific capacity, which is attributed to the inherent atom-electron-capacity correspondence. We observed the surface atom knockout process at different stages and studied the evolution of the chemical environment. The alloy catalyst achieves a higher current density for oxygen reduction reaction compared to the original alloy and Pt/C. This work provides an atomic fabrication method for material synthesis and regulation toward the wide applications in catalysis, energy, and others.

Highly Solubilized Urea as Effective Proton Donor-Acceptors for Durable Zinc-Ion Storage Beyond Single-Anion Selection Criteria.

Urea, as one of the most sustainable organic solutes, denies the high salt consumption in commercial electrolytes with its peculiar solubility in water. The bi-mixture of urea-H2O shows the eutectic feature for increased attention in aqueous Zn-ion electrochemical energy storage (AZEES) technologies. While the state-of-the-art aqueous electrolyte recipes are still pursuing the high-concentrated salt dosage with limited urea adoption and single-anion selection category. Here, a dual-anion urea-based (DAU) electrolyte composed of dual-Zn salts and urea-H2O-induced solutions is reported, contributing to a stable electric double-layer construction and in situ organic/inorganic SEI formation. The optimized ZT2S0.5-20U electrolytes show a high initial Coulombic efficiency of 93.2% and durable Zn-ion storage ≈4000 h regarding Zn//Cu and Zn//Zn stripping/plating procedures. The assembled Zn//activated carbon full cells maintain ≈100% capacitance over 50 000 cycles at 4 A g-1 in coin cell and ≈98% capacitance over 20 000 cycles at 1 A g-1 in pouch cell setups. A 12 × 12 cm2 pouch cell assembly illustrates the practicality of AZEES devices by designing the cheap, antifreezing, and nonflammable DAU electrolyte system coupling proton donor-acceptor molecule and multi-anion selection criteria, exterminating the critical technical barriers in commercialization.

[Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway].

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Organic-Platinum Hybrids for Covalent Binding of G-Quadruplexes: Structural Basis and Application to Cancer Immunotherapy.

G-quadruplexes (G4s) have been revived as promising therapeutic targets with the development of immunotherapy, but the G4-mediated immune response remains unclear. We designed a novel class of G4-binding organic-platinum hybrids, L1 -cispt and L1 -transpt, with spatial matching for G4 binding and G4 DNA reactivity for binding site locking. The solution structure of L1 -transpt-MYT1L G4 demonstrated the effectiveness of the covalent binding and revealed the covalent binding-guided dynamic balance, accompanied by the destruction of the A5-T17 base pairs to achieve the covalent binding of the platinum unit to N7 of the G6 residue. Furthermore, L1 -cispt- and L1 -transpt-mediated genomic dysfunction could activate the retinoic acid-induced gene I (RIG-I) pathway and induce immunogenic cell death (ICD). The use of L1 -cispt/L1 -transpt-treated dying cells as therapeutic vaccines stimulated a robust immune response and effectively inhibited tumor growth in vivo. Our findings highlight the importance of the rational combination of specific spatial recognition and covalent locking in G4-trageting drug design and their potential in immunotherapy.

Structural Basis of Pyridostatin and Its Derivatives Specifically Binding to G-Quadruplexes.

The nucleic acid G-quadruplex (G4) has emerged as a promising therapeutic target for a variety of diseases such as cancer and neurodegenerative disease. Among small-molecule G4-binders, pyridostatin (PDS) and its derivatives (e.g., PyPDS) exhibit high specificity to G4s, but the structural basis for their specific recognition of G4s remains unknown. Here, we presented two solution structures of PyPDS and PDS with a quadruplex-duplex hybrid. The structures indicate that the rigid aromatic rings of PyPDS/PDS linked by flexible amide bonds match adaptively with G-tetrad planes, enhancing π-π stacking and achieving specific recognition of G4s. The aliphatic amine side chains of PyPDS/PDS adjust conformation to interact with the phosphate backbone via hydrogen bonding and electrostatic interactions, increasing affinity for G4s. Moreover, the N-H of PyPDS/PDS amide bonds interacts with two O6s of G-tetrad guanines via hydrogen bonding, achieving a further increase in affinity for G4s, which is different from most G4 ligands. Our findings reveal from structural perspectives that the rational assembly of rigid and flexible structural units in a ligand can synergistically improve the selectivity and affinity for G4s through spatial selective and adaptive matching.

Enhanced Adsorption and Separation of Xenon over Krypton via an Unsaturated Calcium Center in a Metal-Organic Framework.

Krypton (Kr) and xenon (Xe) are nowadays widely applied in technical and industrial fields. Separating and collecting highly pure Xe from nuclear facilities are necessary and urgent. However, the technology is limited due to the inert nature of Xe and other interferential factors. In this work, a calcium-based metal-organic framework, Ca-SINAP-1, which comprises a three-dimensional microporous framework with a suitable pore width, was researched for xenon and krypton separation through both experimental and theoretical methods. Ca-SINAP-1, synthesized in solvothermal and gamma ray conditions, features accessible open-metal sites, exhibits a high Xe/Kr selectivity of 10.32, and owns a Xe adsorption capacity of 2.87 mmol/g at room temperature (1.0 bar). Particularly, its excellent chemical stability (from pH 2 to 13) and thermal stability (up to 550 °C), as well as radiation-resistance (up to 400 kGy ß irradiations), render this material a promising candidate for radioactive inert gases treatment.

Spatial Matching Selectivity and Solution Structure of Organic-Metal Hybrid to Quadruplex-Duplex Hybrid.

The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand L1 Pt(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-L1 Pt(dien) complex was determined by NMR. The structure reveals that L1 Pt(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via π-π stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures.

Association between well-characterized gene polymorphisms and the hypnosis response caused by sevoflurane-induced anaesthesia.

WHAT IS KNOWN AND OBJECTIVE: Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood. In this study, we explored the effects of genetic variations on sevoflurane-induced hypnosis. METHODS: Sixty-six SNPs in 18 candidate genes were genotyped using MALDI-TOF MassARRAY in a discovery cohort containing 161 patients administered sevoflurane. Significant polymorphisms were assessed in a validation cohort containing 265 patients. RESULTS AND DISCUSSION: Three polymorphisms (GRIN1 rs28681971, rs79901440 and CHRNA7 rs72713539) were significantly associated with the time to loss of consciousness in patients treated with sevoflurane in the discovery cohort; among them, GRIN1 rs28681971 showed a significant association even after false discovery rate (FDR) correction (pFDR  = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (pFDR  = 0.027, 0.034). Combined assessments and meta-analysis of the results of the two cohorts indicated that the C carriers of rs28681971 and T carriers of rs79901440 in GRIN1 require a longer time to achieve unconsciousness. WHAT IS NEW AND CONCLUSION: These findings suggest that GRIN1 polymorphisms are associated with sevoflurane-induced unconsciousness. Thus, the genotypes of GRIN1 may serve as novel and meaningful biomarkers for sevoflurane-induced unconsciousness.

Simultaneous Quantitative Analysis of Six Isothiazolinones in Water-Based Adhesive Used for Food Contact Materials by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS).

In this study, a target analytical approach using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed to simultaneously determine six isothiazolinones containing 2-Methylisothiazol-3(2H)-one (MI), 5-Chloro-2-methyl-4-isothiazolin-3-one (CMI), 1,2-benzisothiazolin-3-one (BIT), 2-Octyl-3(2H)-isothiazolinone (OIT), Dichlorooctylisothiazolinone (DCOIT), and 2-methyl-1,2-benzisothiazolin-3-one (MBIT) in water-based adhesive used for food contact materials. The main factors affecting extraction efficiency such as extraction method, extraction time, extraction solvent, and solid-liquid ratio have been evaluated by using real adhesive samples. Multiple-reaction monitoring (MRM) was used for the qualitative and quantitative analyses of targeted isothiazolinones. This method was demonstrated as an effective and reliable technique for detecting multiple isothiazolinones with satisfactory recoveries (81.5~107.3%), and the limits of detection (LOD) and quantification (LOQ) were obtained at a low level. This method was validated and applied to the determination of six isothiazolinones in commercial water-based adhesives. The present results revealed that these adhesives contained a combination of isothiazolinones (BIT, MI, CMI, and MBIT) with the concentration ranging from 2.27 to 123.5 mg/kg. To our knowledge, it is the first time it has been reported that MBIT was detected in water-based adhesives used for food contact materials, which requires a further investigation for its migration to food and the risk to human health.

Identification of diverse modulators of central and peripheral circadian clocks by high-throughput chemical screening.

The circadian clock coordinates daily oscillations of essential physiological and behavioral processes. Conversely, aberrant clocks with damped amplitude and/or abnormal period have been associated with chronic diseases and aging. To search for small molecules that perturb or enhance circadian rhythms, we conducted a high-throughput screen of approximately 200,000 synthetic compounds using Per2lucSV reporter fibroblast cells and validated 11 independent classes of molecules with Bmal1:luciferase reporter cells as well as with suprachiasmatic nucleus and peripheral tissue explants. Four compounds were found to lengthen the period in both central and peripheral clocks, including three compounds that inhibited casein kinase Iε in vitro and a unique benzodiazepine derivative acting through a non-GABA(A) receptor target. In addition, two compounds acutely induced Per2lucSV reporter bioluminescence, delayed the rhythm, and increased intracellular cAMP levels, but caused rhythm damping. Importantly, five compounds shortened the period of peripheral clocks; among them, four compounds also enhanced the amplitude of central and/or peripheral reporter rhythms. Taken together, these studies highlight diverse activities of drug-like small molecules in manipulating the central and peripheral clocks. These small molecules constitute a toolbox for probing clock regulatory mechanisms and may provide putative lead compounds for treatment of clock-associated diseases.

[Preparation and release behaviour of mesoporous silica/ethylcellulose sustained-release mini-matrix].

Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.

Separator designs for aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) are attracting worldwide attention due to their multiple merits such as extreme safety, low cost, feasible assembly, and environmentally friendly enabled by water-based electrolytes. At present, AZIBs have experienced systematic advances in battery components including cathode, anode, and electrolyte, whereas research involving separators is insufficient. The separator is the crucial component of AZIBs through providing ion transport, forming contact with electrodes, serving as a container for electrolyte, and ensuring the efficient battery operation. Considering this great yet ignored significance, it is timely to present the latest advances in design strategies, the systematic classification and summary of separators. We summarize the separator optimization strategies mainly along two approaches including the modification of the frequently used glass fiber and the exploitation of new separators. The advantages and disadvantages of the two strategies are analyzed from the material types and the characteristics of different strategies. The effects and mechanisms of various materials on regulating the uniform migration and deposition of Zn2+, balancing the excessively concentrated nucleation points, inhibiting the growth of dendrites, and the occurrence of side reactions were discussed using confinement, electric field regulation, ion interaction force, desolvation, etc. Finally, potential directions for further improvement and development of AZIBs separators are proposed, aiming at providing helpful guidance for this booming field.

The prevalence of oral frailty among older adults: a systematic review and meta­analysis.

BACKGROUND: In recent years, oral frailty was proposed as a new concept regarding dental and oral health in older adults. Poor oral health is linked to preserving general health and has become a geriatric public health problem that deeply affects healthy aging. While in present, evidence on the prevalence associated with oral frailty in older adults remains unclear. OBJECTIVE: To systematically evaluate the prevalence of oral frailty among older adults, stratified by relevant factors such as gender, source, study design, region, and the evaluation scales for oral frailty and provide an evidence-based foundation for healthcare professionals and policymakers to formulate relevant measures. METHODS: Ten electronic databases were systematically searched from inception to September 2023, including PubMed, Web of Science, Embase, PsycINFO, The Cochrane Library, CINAHL, China National Knowledge Infrastructure Database (CNKI), Chinese Biomedical Database (Sinomed), Weipu Database, and Wanfang database. Based on the Stata 15.0 software package, a random effect model was used to calculate the pooled prevalence of oral frailty among older adults. In addition, sensitivity analysis, subgroup analysis, and meta-regression were conducted based on different study characteristics to detect heterogeneity sources. Funnel plots, Begg's and Egger's tests were used to evaluate the publication bias. RESULTS: Eighteen studies with a total of 12,932 older adults were included for meta-analysis. The pooled prevalence of oral frailty and oral pre-frailty was 24% (95% CI: 20-28%) and 57% (95% CI: 52-61%) respectively. Based on different assessment tools of oral frailty, the pooled prevalence of oral frailty was higher when using the OFI-8 scale (44.1%; 95% CI: 35.4-52.8%) than the OFI-6 scale (18.3%; 95% CI: 15.8-20.8%) or OF checklist (22.1%; 95% CI: 17.4-26.7%). The prevalence of oral frailty was higher among older adults in females (23.8%; 95% CI: 18.4-29.2%), hospital settings (31%, 95% CI: 16.6-45.5%), cross-sectional design (26.7%, 95% CI: 19.2-34.2%), and China (45.9%, 95% CI: 34.4-57.3%). CONCLUSIONS: Our study showed that oral frailty was common among older adults and various characteristics may affect its prevalence. Thus, healthcare professionals and policymakers should take oral frailty seriously in clinical practice and program planning and develop more preventive measures for oral frailty among older adults.

Two new species of Paraphlomis (Lamiales, Lamiaceae) from limestone karsts in Guangdong Province, China.

Paraphlomisqingyuanensis and P.baiwanensis (Lamiaceae), two new species from the limestone area in Guangdong Province, China, are described. Morphologically, both species belong to P.ser.Subcoriaceae C.Y. Wu & H.W. Li. A close relationship between the two new and P.subcoriacea was revealed by molecular phylogenetic analyses based on ETS and ITS. Further morphological and population genetic evidence indicated that they are distinct species in Paraphlomis. According to the IUCN Red List Categories and Criteria, P.qingyuanensis and P.baiwanensis were assessed as Endangered (EN) and Deficient (DD), respectively.

G-quadruplex-guided cisplatin triggers multiple pathways in targeted chemotherapy and immunotherapy.

G-quadruplexes (G4s) are atypical nucleic acid structures involved in basic human biological processes and are regulated by small molecules. To date, pyridostatin and its derivatives [e.g., PyPDS (4-(2-aminoethoxy)-N 2,N 6-bis(4-(2-(pyrrolidin-1-yl) ethoxy) quinolin-2-yl) pyridine-2,6-dicarboxamide)] are the most widely used G4-binding small molecules and considered to have the best G4 specificity, which provides a new option for the development of cisplatin-binding DNA. By combining PyPDS with cisplatin and its analogs, we synthesize three platinum complexes, named PyPDSplatins. We found that cisplatin with PyPDS (CP) exhibits stronger specificity for covalent binding to G4 domains even in the presence of large amounts of dsDNA compared with PyPDS either extracellularly or intracellularly. Multiomics analysis reveals that CP can effectively regulate G4 functions, directly damage G4 structures, activate multiple antitumor signaling pathways, including the typical cGAS-STING pathway and AIM2-ASC pathway, trigger a strong immune response and lead to potent antitumor effects. These findings reflect that cisplatin-conjugated specific G4 targeting groups have antitumor mechanisms different from those of classic cisplatin and provide new strategies for the antitumor immunity of metals.

NKCC1 upregulation disrupts chloride homeostasis in the hypothalamus and increases neuronal activity-sympathetic drive in hypertension.

Hypertension is a major risk factor for coronary artery disease, stroke, and kidney failure. However, the etiology of hypertension in most patients is poorly understood. Increased sympathetic drive emanating from the hypothalamic paraventricular nucleus (PVN) plays a major role in the development of hypertension. Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the brain is critically involved in maintaining chloride homeostasis and in neuronal responses mediated by GABA(A) receptors. Here we present novel evidence that the GABA reversal potential (E(GABA)) of PVN presympathetic neurons undergoes a depolarizing shift that diminishes GABA inhibition in spontaneously hypertensive rats (SHRs). Inhibition of NKCC1, but not KCC2, normalizes E(GABA) and restores GABA inhibition of PVN neurons in SHRs. The mRNA and protein levels of NKCC1, but not KCC2, in the PVN are significantly increased in SHRs, and the NKCC1 proteins on the plasma membrane are highly glycosylated. Inhibiting NKCC1 N-glycosylation restores E(GABA) and GABAergic inhibition of PVN presympathetic neurons in SHRs. Furthermore, NKCC1 inhibition significantly reduces the sympathetic vasomotor tone and augments the sympathoinhibitory responses to GABA(A) receptor activation in the PVN in SHRs. These findings suggest that increased NKCC1 activity and glycosylation disrupt chloride homeostasis and impair synaptic inhibition in the PVN to augment the sympathetic drive in hypertension. This information greatly improves our understanding of the pathogenesis of hypertension and helps to design better treatment strategies for neurogenic hypertension.

Casein kinase 2-mediated synaptic GluN2A up-regulation increases N-methyl-D-aspartate receptor activity and excitability of hypothalamic neurons in hypertension.

Increased glutamatergic input, particularly N-methyl-D-aspartate receptor (NMDAR) activity, in the paraventricular nucleus (PVN) of the hypothalamus is closely associated with high sympathetic outflow in essential hypertension. The molecular mechanisms underlying augmented NMDAR activity in hypertension are unclear. GluN2 subunit composition at the synaptic site critically determines NMDAR functional properties. Here, we found that evoked NMDAR-excitatory postsynaptic currents (EPSCs) of retrogradely labeled spinally projecting PVN neurons displayed a larger amplitude and shorter decay time in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats. Blocking GluN2B caused a smaller decrease in NMDAR-EPSCs of PVN neurons in SHRs than in WKY rats. In contrast, GluN2A blockade resulted in a larger reduction in evoked NMDAR-EPSCs and puff NMDA-elicited currents of PVN neurons in SHRs than in WKY rats. Blocking presynaptic GluN2A, but not GluN2B, significantly reduced the frequency of miniature EPSCs and the firing activity of PVN neurons in SHRs. The mRNA and total protein levels of GluN2A and GluN2B in the PVN were greater in SHRs than in WKY rats. Furthermore, the GluN2B Ser(1480) phosphorylation level and the synaptosomal GluN2A protein level in the PVN were significantly higher in SHRs than in WKY rats. Inhibition of protein kinase CK2 normalized the GluN2B Ser(1480) phosphorylation level and the contribution of GluN2A to NMDAR-EPSCs and miniature EPSCs of PVN neurons in SHRs. Collectively, our findings suggest that CK2-mediated GluN2B phosphorylation contributes to increased synaptic GluN2A, which potentiates pre- and postsynaptic NMDAR activity and the excitability of PVN presympathetic neurons in hypertension.

Effects of folic acid and folic acid plus zinc supplements on the sperm characteristics and pregnancy outcomes of infertile men: A systematic review and meta-analysis.

Background: Folic acid and zinc supplements have been used to treat male infertility, but their efficacy is still debated. Objective: To systematically evaluate the effects of folic acid and folic acid plus zinc supplements on sperm characteristics and pregnancy outcomes of infertile men. Methods: An online systematic search was performed using PubMed, Cochrane Library, and EMBASE databases from inception to August 1, 2022. The goal was to identify randomized controlled trials (RCTs) that used folic acid or folic acid plus zinc to improve sperm characteristics of infertile men. Data were extracted by two investigators who independently screened the literature and assessed for quality according to the criteria. The meta-analysis was performed using RevMan 5.4 software. Results: A total of 8 RCT studies involving 2168 patients were included. The results showed that compared with the controls, folic acid significantly increased sperm motility (MD, 3.63; 95% CI, -1.22 to 6.05; P = 0.003), but did not affect the sperm concentration (MD, 2.53; 95% CI, -1.68 to 6.73; P = 0.24) and sperm morphology (MD, -0.02; 95% CI, -0.29 to 0.24; P = 0.86) in infertile men. Folic acid plus zinc did not affect sperm concentration (MD, 1.87; 95% CI, -1.39 to 5.13; P = 0.26), motility (MD, 1.67; 95% CI, -1.29 to 4.63; P = 0.27), and morphology (MD, -0.05; 95% CI, -0.27 to 0.18; P = 0.69) in infertile men. Secondary results showed that compared with a placebo, folic acid alone had a higher rate of pregnancy in transferred embryos (35.6% vs. 20.4%, P = 0.082), but the difference was not significant. Folic acid plus zinc did not affect pregnancy outcomes. Conclusions: Based on the meta-analysis, no significant improvements in sperm characteristics with folic acid plus zinc supplements were seen. However, folic acid alone has demonstrated the potential to improve sperm motility and in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes. This indicates that folic acid supplements alone may be a viable treatment option for male infertility.

GRN is a prognostic biomarker and correlated with immune infiltration in glioma: A study based on TCGA data.

Background: Among primary brain tumors, gliomas are associated with a poor prognosis and a median survival that varies depending on the tumor grade and subtype. As the most malignant form of glioma, glioblastoma (GBM) constitutes a significant health concern. Alteration in granulin(GRN) has been proved to be accountable for several diseases. However, the relationship between GRN and GBM remains unclear. We evaluated the role of GRN in GBM through The Cancer Genome Atlas (TCGA) database. Methods: First, we assessed the relationship between GRN and GBM through the GEPIA database. Next, the relationship between GRN and GBM prognosis was analyzed by logistic regression and multivariate cox methods. Using CIBERSORT and the GEPIA correlation module, we also investigated the link between GRN and immune infiltrates in cancer. Using the TCGA data, a gene set enrichment analysis (GSEA) was performed. We also employed Tumor Immune Estimation Resource (TIMER) to examine the data set of GRN expression and immune infiltration level in GBM and investigate the cumulative survival in GBM. We also validated tissues from GBM patients by Western blotting, RT-qPCR, and immunohistochemistry. Results: Increased GRN expression was shown to have a significant relationship to tumor grade in a univariate study utilizing logistic regression. Furthermore, multivariate analysis disclosed that GRN expression down-regulation is an independent predictive factor for a favorable outcome. GRN expression level positively correlates with the number of CD4+ T cells, neutrophils, macrophages, and dendritic cells (DCs) that infiltrate a GBM. The GSEA also found that the high GRN expression phenotype pathway was enriched for genes involved in immune response molecular mediator production, lymphocyte-mediated immunity, cytokine-mediated signaling pathway, leukocyte proliferation, cell chemotaxis, and CD4+ alpha beta T cell activation. Differentially enriched pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) include lysosome, apoptosis, primary immunodeficiency, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and B cell receptor signaling pathway. Validated result showed that GRN was upregulated in GBM tissues. These results suggested that GRN was a potential indicator for the status of GBM. Conclusion: GRN is a prognostic biomarker and correlated with immune infiltrates in GBM.

Two-dimensional materials as sodium-ion battery anodes: The mass transfer and storage mechanisms of "fat" Na.

Sodium-ion batteries (SIBs) with abundant resource and high safety are attracting intensive interest from both research and industry communities in meeting the ever-increasing energy demands. Despite the rapid advance of SIBs, it is difficult yet necessary to enhance the cycling and rate performance at anode due to the sluggish kinetics of "fat" Na+. This review provides an overview of two-dimensional (2D) nanomaterials with a short ion diffusion pathway and a superior active sites exposure from the perspectives of synthesis, material chemistry, and structure engineering. We present the design principle of ideal carbon materials in SIBs. Moreover, we discuss the structure and chemistry regulations of different 2D materials to promote the efficient ion mass transfer and storage according to the different mechanisms of alloying, conversion, and insertion. Finally, we propose the remaining challenges and the possible solutions, in hope of guiding the future development of this booming field.