Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China.

BACKGROUND: Prior studies have noted great variability in the plasma levels of risperidone (RIS). Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption, metabolism, and other predictors of metabolic dysregulation; however, these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain. AIM: To ascertain the characteristics of chronic schizophrenic patients treated with RIS, and to assess their relationship with plasma RIS levels. METHODS: This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service. The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography. The patients' demographic and clinical characteristics, and psychopathologies were assessed, and the associations between clinical variables and plasma levels of RIS were explored. RESULTS: Male patients received higher doses of RIS than female ones, but plasma concentrations of RIS and risperidone + 9-hydroxyrisperidone (active moiety) were higher in female patients. Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS) were significantly positively correlated with plasma concentrations of risperidone + 9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects. In male subjects, we found a statistically significant positive correlation between the concentrations of risperidone + 9-hydroxyrisperidone in plasma/(dose × kg) and age, mean PANSS negative subscale scores, mean PANSS general psychopathology subscale scores, and mean PANSS total scores. CONCLUSION: Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Symmetry-breaking charge separation in a null-excitonic 3-dimensional rigid nonconjugated trimer.

Photoinduced symmetry-breaking charge separation (SB-CS) has been extensively observed in various oligomers and aggregates, which holds great potential for robust artificial solar energy conversion systems. It attaches great importance to the precise manipulation of interchromophore electronic coupling in realizing efficient SB-CS. The emerging studies on SB-CS suggested that it could be realized in null-excitonic aggregates, and a long-lived SB-CS state was observed, which offers an advanced platform and has gathered immense attention in the SB-CS field. Here, we unveiled the null-exciton coupling induced ultrafast SB-CS in a rigid polycyclic aromatic hydrocarbon framework, triperyleno[3,3,3]propellane triimides (TPPTI), in which three chromophores were attached through a nonconjugated bridge. Through a combination of theoretical calculations and steady-state absorption results, we demonstrated that this nonconjugated TPPTI possesses negligible exciton coupling. Increased solvent polarity was found to significantly enhance state mixing between local excited and charge transfer states. Using transient absorption spectroscopy, ultrafast SB-CS was observed in highly polar dimethylformamide, facilitated by a selective hole-transfer coupling and a favorable charge separation free energy (ΔGCS). Additionally, the rate ratio between SB-CS and charge recombination was at least high to 1800 in dimethylformamide. This investigation provides profound insights into the role of null-exciton coupling in dominating ultrafast SB-CS in multichromophoric systems.

Ruthenium-Based Binary Alloy with Oxide Nanosheath for Highly Efficient and Stable Oxygen Evolution Reaction in Acidic Media.

Traditional noble metal oxide, such as RuO2, is considered a benchmark catalyst for acidic oxygen evolution reaction (OER). However, its practical application is limited due to sluggish activity and severe electrochemical corrosion. In this study, Ru-Fe nanoparticles loading on carbon felt (RuFe@CF) is synthesized via an ultrafast Joule heating method as an active and durable OER catalyst in acidic conditions. Remarkably low overpotentials of 188 and 269 mV are achieved at 10 and 100 mA cm-2, respectively, with a robust stability up to 620 h at 10 mA cm-2. When used as an anode in a proton exchange membrane water electrolyzer, the catalyst shows more than 250 h of stability at a water-splitting current of 200 mA cm-2. Experimental characterizations reveal the presence of a Ru-based oxide nanosheath on the surface of the catalyst during OER tests, suggesting a surface reconstruction process that enhances the intrinsic activity and inhibits continuous metal dissolution. Moreover, density functional theory calculations demonstrate that the introduction of Fe into the RuFe@CF catalyst reduces the energy barrier and boosts its activities. This work offers an effective and universal strategy for the development of highly efficient and stable catalysts for acidic water splitting.

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys.

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

Efficient Intersystem Crossing in Extended Helical Perylene Diimide Dimers with Chalcogen-Annulation.

The properties and formation mechanisms of the triplet state have been widely investigated since they are crucial intermediates in photo functional devices. Specifically, helical PDI dimers, horizontal expanded π-conjugated derivatives of PDI, have shown outstanding performance as electron acceptors in enhancing the performance of photovoltaics. Therefore, the exploration of triplet generation in helical PDI dimers plays a crucial role in understanding the mechanisms and excavating their further application. We make use of Se-annulation to induce intersystem crossing (ISC) in helical PDI dimers and further explore the triplet evolution process systematically as the number of Se atoms increases by transient absorption spectroscopy and the hole-electron analysis method. It shows that the twisted molecular conformation has paved the way for potential ISC in a parent molecule PDI2. The incorporation of Se atoms can result in evident promotion in the efficiency of ISC (ϕTPDI2-2Se = 96.9%) compared to the parent molecule PDI2 (ϕTPDI2 = 26.5%), indicating that chalcogen-annulation is also an efficient strategy in a π-extended system. Our results provide useful insights for understanding the triplet evolution process, which can help broaden the application of the π-extended PDI system into high-performance photovoltaics.

Isoflavones isolated from the fruits of Ficus altissima and their anti-proliferative activities.

Ficus altissima, also known as lofty fig, is a monoecious plant from the Moraceae family commonly found in southern China. In this study, we isolated and identified one new isoflavone (1), three new hydroxycoumaronochromones (2a, 2b and 3a) and 12 known compounds from the fruits of F. altissima. Their chemical structures were determined using spectroscopic analysis methods. We also tested all the isolated compounds for their anti-proliferative activities against eight human tumour cell lines (A-549, AGS, K562, K562/ADR, HepG2, HeLa, SPC-A-1 and CNE2) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Our experiments showed that compound 6 exhibited obvious anti-proliferative activity against the K562 cell line with an IC50 value of 1.55 µM. Additionally, compounds 8 and 9 showed significant anti-proliferative activities against the AGS and K562 cell lines, respectively. Moreover, compound 6 induced apoptosis in K562 cells through the caspase family signalling pathway.

Relevance and antimicrobial resistance profile of Klebsiella pneumoniae in neonatal sepsis.

BACKGROUND: Newborns are particularly susceptible to infection in hospitals, with neonatal sepsis being the most common infection symptom and the third leading cause of neonatal death. Klebsiella pneumoniae is a gram-negative bacterium of Enterobacteriaceae, which is a common pathogen of neonatal septicemia. In this study, we will analyze and evaluate the current status, clinical characteristics, and drug resistance of Klebsiella pneumoniaesepsis infection in Neonatal Intensive Care Unit (NICU), with the aim of providing effective basis for timely and accurate clinical diagnosis and treatment in clinical practice. METHODS: Statistical analysis was performed on 75 cases of Enterobacteriaceae septicemia in infants admitted to NICU in a special obstetrics and gynecology hospital in Shanghai from January 2020 to June 2022. Based on bacterial identification, isolates were divided into the Klebsiella pneumoniae (KP) group (n = 49) and the non-KP Enterobacteriaceae group (n = 26). The infection, clinical characteristics, and bacterial resistance of the two groups of infected patients were compared. RESULTS: Comparing the clinical characteristics of the two groups, the results showed that most of the subjects in the KP and non-KP groups were premature infants, accounting for 100% and 92.3% of subjects, respectively; late onset was the main disease in both groups, accounting for 93.9% and 80.8% of subjects, respectively. All patients received Peripherally Inserted Central Catheter(PICC). The levels of pro calcitonin and CRP (C-reactive protein) were significantly higher in the KP group compared with those in the non-KP group (p < .05). At the same time, the incidence of thrombocytopenia in the KP group was significantly higher than that in the non-KP group (p < .05). The proportion of antimicrobial drug exposure in the KP group is higher than that in the non-KP group. The drug resistance of the KP group to ceftazidime, ceftriaxone, cefepime, ampicillin/sulbactam, aztreonam, ciprofloxacin and compound sulfamethoxazole was significantly higher than that of the non-KP group, whereas the drug resistance rate to cefotetan, gentamycin and to bramycin was significantly lower than that of the non-KP group, Statistically significant differences (p < .05). 38 cases of Klebsiella pneumoniae producing ESBLs were tested for related resistance genes. The results showed that the main resistance types were SHV and TEM, with detection rates of 60.6% and 28.9%. CONCLUSIONS: This study shows that neonatal sepsis caused by Klebsiella pneumoniae infection has a high incidence and drug resistance in premature and low birth weight infants, and has become a serious public health problem; Clinicians should pay attention to differential diagnosis, Reasonable selection of antibiotics to reduce the generation of drug-resistant bacteria.

Appending Coronene Diimide with Carbon Nanohoops Allows for Rapid Intersystem Crossing in Neat Film.

The development of innovative triplet materials plays a significant role in various applications. Although effective tuning of triplet formation by intersystem crossing (ISC) has been well established in solution, the modulation of ISC processes in the solid state remains a challenge due to the presence of other exciton decay channels through intermolecular interactions. The cyclic structure of cycloparaphenylenes (CPPs) offers a unique platform to tune the intermolecular packing, which leads to controllable exciton dynamics in the solid state. Herein, by integrating an electron deficient coronene diimide (CDI) unit into the CPP framework, a donor-acceptor type of conjugated macrocycle (CDI-CPP) featuring intramolecular charge-transfer (CT) interaction was designed and synthesized. Effective intermolecular CT interaction resulting from a slipped herringbone packing was confirmed by X-ray crystallography. Transient spectroscopy studies showed that CDI-CPP undergoes ISC in both solution and the film state, with triplet generation time constants of 4.5 ns and 238 ps, respectively. The rapid triplet formation through ISC in the film state can be ascribed to the cooperation between intra- and intermolecular charge-transfer interactions. Our results highlight that intermolecular CT interaction has a pronounced effect on the ISC process in the solid state, and shed light on the use of the characteristic structure of CPPs to manipulate intermolecular CT interactions.

Ultrafine grinding improves the nutritional, physicochemical, and antioxidant activities of two varieties of whole-grain highland barley.

Effects of ultrafine grinding on the nutritional profile, physicochemical properties, and antioxidant activities of whole-grain highland barley (HB) including white highland barley (WHB) and black highland barley (BHB) were studied. Whole-grain HB was regularly ground and sieved through 80 mesh get 80 M powder, and HB was ultrafine grounded and sieved through 80 mesh, 150 mesh, and 200 mesh get 80UMM, 150UMM, and 200UMM samples. Particle size of WHB and BHB reduced significantly after ultrafine grinding. As the particle size decreased, moisture content of WHB and BHB decreased significantly, whereas fat content increased significantly. Redistribution of fiber components in WHB and BHB from insoluble to soluble fractions was also observed. Wherein, content of soluble pentosan of WHB and BHB increased significantly from 0.56% and 0.78% (80 M) to 0.91% and 1.14% (200UMM), respectively. Damaged starch of WHB and BHB increased significantly from 8.16% and 8.21% (80 M) to 10.29% and 10.07% (200UMM), respectively. Content of phenolic acid and flavonoid of WHB and BHB and associated antioxidant capacity were increased after ultrafine grinding. Color of L* value increased significantly, a* and b* values decreased significantly, indicating the whiteness of WHB and BHB was increased after ultrafine grinding. Pasting temperature of WHB and BHB decreased, whereas peak viscosity increased. X-ray diffraction patterns of HB showed typical A- and V-style polymorphs and the relative crystallinity of HB decreased as the particle size decreased. Taken together, ultrafine grinding has shown great potential in improving the nutritional, physiochemical, and antioxidant properties of whole-grain HB. Our research findings could help better understand the ultrafine grinded whole grain HB in food industry.

Advances in the differentiation of pluripotent stem cells into vascular cells.

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: A bidirectional Two-sample mendelian randomization analysis.

PURPOSE: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis whether a causal relationship exists and provides some evidence of causality. METHODS: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS). We used inverse variable weighting (IVW) as the primary analysis method. In addition, we simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. RESULTS: The results of the IVW method of MR analysis showed that 8 immunocyte phenotypes were positively associated with osteonecrosis (P<0.05, OR > 1); 18 immunocyte phenotypes were negatively associated with osteonecrosis (P<0.05, OR<1), none of which were heterogeneous or horizontally pleiotropic (P > 0.05) or reverse causality. In addition to this, in reverse MR, osteonecrosis was positively associated with 10 additional immunocyte phenotypes (P<0.05, OR > 1) and negatively associated with 14 immunocyte phenotypes (P<0.05, OR<1). And none of them had heterogeneity and horizontal pleiotropy (P > 0.05) or reverse causality. CONCLUSIONS: We demonstrated a complex causal relationship between multiple immune phenotypes and osteonecrosis through a comprehensive two-way two-sample MR analysis, highlighting the complex pattern of interactions between the immune system and osteonecrosis.

Antiproliferative piperidine alkaloids from the leaves of Alocasia macrorrhiza.

Seventeen piperidine alkaloids, including 15 previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol alkaloids and a previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3-ol alkaloid, were isolated from the leaves of Alocasia macrorrhiza (L.) Schott. Their planar structures and configurations were elucidated based on HR-ESI-MS, 1D and 2D NMR, Snatzke's method, modified Mosher method, single-crystal X-ray crystallography, as well as quantum chemical calculation. It was found that ΔδH5b-H5a can be used to elucidate the relative configuration of 2,3,4,6-tetrasubstituted piperidine, by analyzing the NMR data of 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol. Antiproliferative activity was evaluated for all of the alkaloids, and compounds 6-8 showed considerable inhibitory activity against K562 cell line, with the IC50 values of 17.24 ± 1.62, 19.31 ± 0.9 and 18.77 ± 1.09µM, respectively. Furthermore, compounds 6 and 7 exerted an antiproliferative effect by inducing apoptosis.

Anti-inflammatory monoterpenes from morinda (Morinda officinalis How.).

Morinda (Morinda officinalis How.) is widely consumed as a functional food owing to its potential to promote health. This study investigated the anti-inflammatory phytochemicals of morinda and isolated 30 monoterpenes, including 6 undescribed iridoids (1, 6, 9-11 and 25), 2 undescribed acyclic monoterpenoids (28, 29), a known acyclic monoterpenoid and 21 known iridoids. Their chemical and stereo-structures were elucidated based on HR-ESI-MS, NMR, 13C-NMR calculations, ECD data and ECD calculations. Notably, compounds 11, 12 and 20 exerted pronounced inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 28.51 ± 1.70, 25.45 ± 4.17 and 29.17 ± 3.71 µM respectively (indomethacin, IC50 of 33.68 ± 2.19 µM). The same compounds exert anti-inflammatory effects by blocking nuclear translocation of nuclear factor κ-B, and down-regulating the expression of inflammatory cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1ß and interleukin-6 at mRNA and protein levels in a dose-dependent manner. These results suggest that moderate consumption of morinda helps prevent and reduce the occurrence of inflammatory-related diseases.

Human transferrin receptor can mediate SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.

lncRNA-056298 Regulates GAP43 and Promotes Cardiac Intrinsic Autonomic Nerve Remodelling in a Canine Model of Atrial Fibrillation Induction after Ganglionated Plexus Ablation.

BACKGROUND: Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown. OBJECTIVES: The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation. METHODS: A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling. RESULTS: The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation. CONCLUSIONS: lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.

Psychological Capital and Its Factors as Mediators Between Interpersonal Sensitivity and Depressive Symptoms Among Chinese Undergraduates.

Purpose: Current interpersonal sensitivity among college students is easily linked to mood disorders such as anxiety, depression and other mood disorders. This study aims to examine the mediating role of psychological capital and its dimensions in the relationship between interpersonal sensitivity and depressive symptoms among undergraduates. Methods: The cross-sectional survey was conducted by using cluster stratified random sampling method across six Chinese universities between November and December 2022. The questionnaire consists of the Interpersonal Sensitivity sub-scale, the Patient Health Questionnaire, the Psychological Capital Questionnaire and the Socio-Demographic Feature Questionnaire. Results: A total of 2580 respondents participated in the survey, with the majority being females (69.73%) and an average age of 19.22±1.28 years. Descriptive and correlation analyses were performed using SPSS v24.0, while direct and indirect effects were analyzed using PROCESS v3.4 macro. The findings revealed that interpersonal sensitivity had a significant direct effect on depression symptoms among undergraduates (ß =0.416, 95% Boot CI [0.380, 0.453], p < 0.001) Additionally, psychological capital and its components were found to be negatively correlated with depression (p < 0.001). Further analysis demonstrated that hope, optimism, and resilience significantly mediated the association between interpersonal sensitivity and depressive symptoms (indirect effect: hope = 0.056, optimism = 0.074, resilience = 0.099; p < 0.001 for all). Conclusion: These results suggest that psychological capital, including its dimensions of hope, optimism, and resilience plays a crucial role in mitigating the negative effects of interpersonal sensitivity on depressive symptoms among undergraduates.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Non-Noble Metal High-Entropy Alloy-Based Catalytic Electrode for Long-Life Hydrogen Gas Batteries.

The development of efficient, stable, and low-cost bifunctional catalysts for the hydrogen evolution/oxidation reaction (HER/HOR) is critical to promote the application of hydrogen gas batteries in large scale energy storage systems. Here we demonstrate a non-noble metal high-entropy alloy grown on Cu foam (NNM-HEA@CF) as a self-supported catalytic electrode for nickel-hydrogen gas (Ni-H2) batteries. Experimental and theoretical calculation results reveal that the NNM-HEA catalyst greatly facilitates the HER/HOR catalytic process through the optimized electronic structures of the active sites. The assembled Ni-H2 battery with NNM-HEA@CF as the anode shows excellent rate capability and exceptional cycling performance of over 1800 h without capacity decay at an areal capacity of 15 mAh cm-2. Furthermore, a scaled-up Ni-H2 battery fabricated with an extended capacity of 0.45 Ah exhibits a high cell-level energy density of ∼109.3 Wh kg-1. Moreover, its estimated cost reaches as low as ∼107.8 $ kWh-1 based on all key components of electrodes, separator and electrolyte, which is reduced by more than 6 times compared to that of the commercial Pt/C-based Ni-H2 battery. This work provides an approach to develop high-efficiency non-noble metal-based bifunctional catalysts for hydrogen batteries in large-scale energy storage applications.

An All-Climate Nonaqueous Hydrogen Gas-Proton Battery.

Rechargeable hydrogen gas batteries, driven by hydrogen evolution and oxidation reactions (HER/HOR), are emerging grid-scale energy storage technologies owing to their low cost and superb cycle life. However, compared with aqueous electrolytes, the HER/HOR activities in nonaqueous electrolytes have rarely been studied. Here, for the first time, we develop a nonaqueous proton electrolyte (NAPE) for a high-performance hydrogen gas-proton battery for all-climate energy storage applications. The advanced nonaqueous hydrogen gas-proton battery (NAHPB) assembled with a representative V2(PO4)3 cathode and H2 anode in a NAPE exhibits a high discharge capacity of 165 mAh g-1 at 1 C at room temperature. It also efficiently operates under all-climate conditions (from -30 to +70 °C) with an excellent electrochemical performance. Our findings offer a new direction for designing nonaqueous proton batteries in a wide temperature range.

A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene.

Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle fibers. Riboflavin therapy has been shown to ameliorate symptoms in some LSM patients who are essentially concerned with multiple acyl-CoA dehydrogenation deficiency (MADD). It is proved that riboflavin responsive LSM caused by MADD is mainly due to ETFDH gene variant (ETFDH-RRMADD). We described here a case with riboflavin responsive LSM and MADD resulting from FLAD1 gene variants (c.1588 C > T p.Arg530Cys and c.1589 G > C p.Arg530Pro, FLAD1-RRMADD). And we compared our patient together with 9 FLAD1-RRMADD cases from literature to 106 ETFDH-RRMADD cases in our neuromuscular center on clinical history, laboratory investigations and pathological features. Furthermore, the transcriptomics study on FLAD1-RRMADD and ETFDH-RRMADD were carried out. On muscle pathology, both FLAD1-RRMADD and ETFDH-RRMADD were proved with lipid storage myopathy in which atypical ragged red fibers were more frequent in ETFDH-RRMADD, while fibers with faint COX staining were more common in FLAD1-RRMADD. Molecular study revealed that the expression of GDF15 gene in muscle and GDF15 protein in both serum and muscle was significantly increased in FLAD1-RRMADD and ETFDH-RRMADD groups. Our data revealed that FLAD1-RRMADD (p.Arg530) has similar clinical, biochemical, and fatty acid metabolism changes to ETFDH-RRMADD except for muscle pathological features.