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1.
Am J Obstet Gynecol MFM ; : 101433, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019211

RESUMO

BACKGROUND: Improved pain control after caesarean section remains a challenging objective. Although both the lateral quadratus lumborum block and acupuncture have been reported to provide superior postoperative analgesia after caesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of lateral quadratus lumborum block and acupuncture following elective caesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton term pregnancies scheduled for caesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or lateral quadratus lumborum block group. Lateral quadratus lumborum block group received bilateral lateral quadratus lumborum block with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy and sham lateral quadratus lumborum block. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 h. Secondary endpoints included pain scores in the first 48 h postoperatively, patient-controlled intravenous analgesia demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (IQR [range]) pain scores at 24 h on movement was similar in patients receiving acupuncture or lateral quadratus lumborum block (3 (2-4) vs. 3 (2-4), respectively; P = 0.40). Patient-controlled intravenous analgesia consumption and pain scores within 48 h postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 h postoperatively (P<0.001), as well as shortened the time to first flatus (P=0.03) and first drinking (P<0.001) compared to lateral quadratus lumborum block. In addition, the median time to mobilization in the lateral quadratus lumborum block group was markedly prolonged compare with acupuncture group (17.0 (15.0-19.0) h vs. 15.3 (13.3-17.0) h, estimated median difference, 1.5; 95%CI, 1-2; P<0.001;). CONCLUSIONS: As a component of multimodal analgesia regimen after caesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to lateral quadratus lumborum block.

3.
Zool Res ; 45(4): 937-950, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39021082

RESUMO

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.


Assuntos
Proteínas Relacionadas à Autofagia , Autofagia , Células-Tronco Neurais , Animais , Células-Tronco Neurais/fisiologia , Células-Tronco Neurais/metabolismo , Camundongos , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Knockout , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , Regulação da Expressão Gênica , Proteínas de Neoplasias
4.
Small ; : e2402141, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953313

RESUMO

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

6.
J Hazard Mater ; 476: 135166, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38991635

RESUMO

Minimization of cadmium (Cd) accumulation in wheat grain (Triticum aestivum L.) is an important way to prevent Cd hazards to humans. However, little is known about the mechanisms of varietal variation of Cd accumulation in wheat grain. This study explores the physiological mechanisms of Cd bioaccumulation through field and hydroponic experiments on two wheat varieties of low-Cd-accumulating variety (L-6331) and high-Cd-accumulating variety (H-6049). Field study showed that average Cd accumulative rates in spikes of H-6049 were 1.57-fold of L-6331 after flowering, ultimately grain-Cd of H-6049 was 1.70-fold of L-6331 in Cd-contaminated farmland. The hydroponic experiment further confirmed that more vegetative tissues of L-6331 were involved in the remobilization of Cd, which jointly mitigated the process of Cd loaded to grains when leaf-cutting conducted after Cd stress. Additionally, the L1 and N1 of L-6331 play an especially important role in regulating Cd remobilization, and the larger EVB areas in N1 have the morphological feature that facilitates the transfer of Cd to L1. Overall results implied that low-Cd-accumulating variety initiated more trade-offs of reproductive growth and Cd remobilizatoin under Cd-stress after flowering compared with high-Cd-accumulating variety, and provided new insights into the processes of Cd loaded into wheat grains among different varieties.

7.
Int J Infect Dis ; : 107169, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002770

RESUMO

BACKGROUND: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. METHODS: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalised for any infectious disease. Descriptive analyses examined standardised incidence, mortality, and case fatality of infections. FINDINGS: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex-differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. INTERPRETATION: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. FUNDING: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.

8.
J Pharm Sci ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004416

RESUMO

Candidemia leaves a trail of approximately 750,000 cases yearly, with a morbidity rate of up to 30%. While Candida albicans still ranks as the most predominantly isolated Candida species, C. glabrata comes in second, with a death rate of 40-50%. Although infections by Candida spp are commonly treated with azoles, the side effects and rise in resistance against it has significantly limited its clinical usage. The current study aims to address the insolubility of piperine and provide an alternative treatment to Candida infection by formulating a stable piperine-loaded O/W nanoemulsion, comprised of Cremophor RH40, Transcutol HP and Capryol 90 as surfactant, co-surfactant, and oil, respectively. Characterization with zetasizer showed the droplet size, polydispersity (PDI) and zetapotential value of the nanoemulsion to be 24.37 nm, 0.453 and -21.10 mV, respectively, with no observable physical changes such as phase separation from thermostability tests. FTIR peaks confirms presence of piperine within the nanoemulsion and TEM imaging visualized the droplet shape and further confirms the droplet size range of 20-24 nm. The MIC90 value of the piperine-loaded nanoemulsion determined with in vitro microbroth dilution assay was approximately 20-50% lower than that of the pure piperine in DMSO, at a range of 0.8-2.0 mg/mL across all Candida spp. tested. Overall, the study showed that piperine can be formulated into a stable nanoemulsion, which significantly enhances its antifungal activity compared to piperine in DMSO.

9.
Small ; : e2403871, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004859

RESUMO

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS2) and semiconductor phase material (SnS2) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS2-SnS2 achieved a specific capacity of 1437.2 mAh g-1 at 0.1 C current density and 805.5 mAh g-1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact.

10.
Chem Commun (Camb) ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007923

RESUMO

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

11.
Stem Cell Res ; 79: 103486, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38968760

RESUMO

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

12.
Chin Med J (Engl) ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030074

RESUMO

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (Ptrend = 0.011) and MCEs (Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction = 0.037). CONCLUSIONS: Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.

13.
Elife ; 132024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963323

RESUMO

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABAA) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABAA receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5) and preferentially binds the folded conformation of GABAA receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABAA receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.


Assuntos
Retículo Endoplasmático , Receptores de GABA-A , Humanos , Células HEK293 , Retículo Endoplasmático/metabolismo , Animais , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética , Ratos , Chaperona BiP do Retículo Endoplasmático/metabolismo , Neurônios/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética
14.
Bioorg Chem ; 151: 107619, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39024806

RESUMO

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

15.
Chin J Integr Med ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028451

RESUMO

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS: CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.

16.
J Environ Manage ; 365: 121586, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38941853

RESUMO

Alpine grasslands are distributed widely on high-elevated ranges and plateaus from the wet tropics to polar regions, accounting for approximately 3% of the world's land area. The Qinghai-Tibetan Plateau (QTP) is the highest and largest plateau in the world, and approximately 60% of the plateau consists of alpine grassland, which is used mainly for grazing animals. Livestock structure was determined in Guinan (GN), Yushu (YS) and Maqu counties (MQ) on the QTP by interviewing 235 local pastoralists. Based on data collected from GN, the livestock carrying capacity was calculated using herbage dry matter biomass intake (LCCm) by the livestock, and the metabolizable energy yield (LCCe) and digestible crude protein (LCCp) available in pasture. The pasture area per household differed among the regions of the QTP, which was the main reason for the difference in livestock stocking rate. The householders raised the appropriate proportion of breeding females and young yaks and sheep in GN and MQ, but not in YS, to maintain a constant turnover. Most pasture in YS was used at the community level, especially in summer. The calculated carrying capacities based on metabolizable energy yield (LCCe) of the pasture and dry matter biomass (LCCm) were similar in most months except for August, when the value of LCCe was higher than LCCm. Based on the digestible protein of the pasture, the calculated livestock carrying capacity overestimated the actual carrying capacity during the herbage growing season from May to September. Appropriate practices should be taken in different regions of QTP, such as providing supplementary feed, especially protein, during the forage non-growing season. Livestock carrying capacity should be adjusted dynamically, and calculated by a number of parameters. The stocking rate should be controlled to optimize livestock production and curb or minimize grassland degradation to generate a sustainable system. This study examined the grasslands and LCC on the QTP, but the results could be applied to grasslands worldwide.


Assuntos
Pradaria , Gado , Animais , Tibet , Biomassa , Criação de Animais Domésticos
17.
Appl Microbiol Biotechnol ; 108(1): 380, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888634

RESUMO

Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked to the multiple organ dysfunction triggered by OSA. However, the role of the CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through the construction of the OSA classic model, we found that the colon tissue of chronic intermittent hypoxia (CIH)-induced mice exhibited an overexpression of the CB1 receptor. The results of hematoxylin-eosin staining and transmission electron microscopy revealed that inhibition of the CB1 receptor could decrease the gap between the mucosa and muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, and promote the recovery of tight junctions of CIH-induced mice. Furthermore, CB1 receptor inhibition reduced the levels of metabolic endotoxemia and inflammatory responses, exhibiting significant protective effects on the colon injury caused by CIH. At the molecular level, through western blotting and real-time polymerase chain reaction techniques, we found that inhibiting the CB1 receptor can significantly increase the expression of ZO-1 and Occludin proteins, which are closely related to the maintenance of intestinal mucosal barrier function. Through 16S rRNA high-throughput sequencing and short-chain fatty acid (SCFA) determination, we found that inhibition of the CB1 receptor increased the diversity of the microbial flora and controlled the makeup of intestinal flora. Moreover, butyric acid concentration and the amount of SCFA-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, were both markedly elevated by CB1 receptor inhibition. The results of the spearman correlation study indicated that Lachnospiraceae showed a positive association with both ZO-1 and Occludin but was negatively correlated with the colon CB1 receptor, IL-1ß, and TNF-α. According to this study, we found that inhibiting CB1 receptor can improve CIH-induced colon injury by regulating gut microbiota, reducing mucosal damage and promoting tight junction recovery. KEY POINTS: •CIH leads to overexpression of CB1 receptor in colon tissue. •CIH causes intestinal flora disorder, intestinal mucosal damage, and disruption of tight junctions. •Inhibition of CB1 receptor can alleviate the colon injury caused by CIH through regulating the gut microbiota, reducing mucosal injury, and promoting tight junction recovery.


Assuntos
Colo , Modelos Animais de Doenças , Mucosa Intestinal , Receptor CB1 de Canabinoide , Animais , Receptor CB1 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/genética , Camundongos , Colo/patologia , Colo/microbiologia , Colo/metabolismo , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Proteína da Zônula de Oclusão-1/metabolismo , Ocludina/metabolismo , Ocludina/genética , Microbioma Gastrointestinal , Junções Íntimas/metabolismo
18.
Small ; : e2403079, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829022

RESUMO

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

19.
Neurosci Bull ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829505

RESUMO

Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

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