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1.
APL Bioeng ; 8(2): 026115, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827498

ABSTRACT

Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H2O2 treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions.

2.
Hum Reprod ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725195

ABSTRACT

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

3.
Food Res Int ; 186: 114319, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729690

ABSTRACT

The "outstanding and unique aged aroma" of Chinese Chenxiang-type baijiu (CXB)-Daoguang 25 (DG25) mainly originates from a "extraordinary storage technology" of Mujiuhai (a wooden container), so it is mysterious and interesting. In this study, an untargeted GC/MS-based metabolomics was used to reveals the volatile differential metabolites for discriminating six different vintages of DG25 combing with chemometrics. A total of 100 volatile metabolites (including unknowns) were extracted and identified, including esters (41%), alcohols (10%) and acids (7%) so on. Finally, 33 differential metabolites were identified as aging-markers. Among them, 25 aging-markers showed a downtrend, including 17 esters such as ethyl acetate, ethyl hexanoate and ethyl palmitate so on. Moreover, it was interesting and to further study that furans showed a significant downtrend. Statistically speaking, ethyl benzoate played an important role in discriminating vintage of 1Y and 3Y, and the other 24 differential metabolites with downtrend discriminating the unstored (0Y-aged) DG25. Eight differential metabolites, such as ethyl octanoate, benzaldehyde, 3-methylbutanol and 1,1-diethoxyaccetal so on increased during aging of DG25, and they played a statistical role in discriminating the 5Y-, 10Y- and 20Y-aged DG25. This study provides a theoretical basis way for the formation mechanism of aging aroma for CXB.


Subject(s)
Gas Chromatography-Mass Spectrometry , Metabolomics , Odorants , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Metabolomics/methods , Volatile Organic Compounds/analysis , Volatile Organic Compounds/metabolism , Odorants/analysis , Wine/analysis , Alcoholic Beverages/analysis
4.
J Nanobiotechnology ; 22(1): 230, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720322

ABSTRACT

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.


Subject(s)
Cancer Vaccines , Lymph Nodes , Manganese Compounds , Mice, Inbred C57BL , Nanoparticles , Ovalbumin , Oxides , Animals , Cancer Vaccines/immunology , Lymph Nodes/immunology , Mice , Ovalbumin/immunology , Ovalbumin/chemistry , Oxides/chemistry , Nanoparticles/chemistry , Manganese Compounds/chemistry , Immunity, Cellular , Female , Cell Line, Tumor , DNA/chemistry , DNA/immunology , Immunotherapy/methods , Melanoma, Experimental/immunology , Melanoma, Experimental/therapy , Particle Size , Antigens, Neoplasm/immunology
5.
Angew Chem Int Ed Engl ; : e202403241, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710651

ABSTRACT

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events, however, the effects of mechanical force on vesicular release has been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channel in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines release by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide a revealing insight on the regulatory effects of mechanical stimuli on vesicular exocytosis.

6.
Front Pharmacol ; 15: 1379338, 2024.
Article in English | MEDLINE | ID: mdl-38738180

ABSTRACT

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

7.
Nucleic Acids Res ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783035

ABSTRACT

High-throughput screening rapidly tests an extensive array of chemical compounds to identify hit compounds for specific biological targets in drug discovery. However, false-positive results disrupt hit compound screening, leading to wastage of time and resources. To address this, we propose ChemFH, an integrated online platform facilitating rapid virtual evaluation of potential false positives, including colloidal aggregators, spectroscopic interference compounds, firefly luciferase inhibitors, chemical reactive compounds, promiscuous compounds, and other assay interferences. By leveraging a dataset containing 823 391 compounds, we constructed high-quality prediction models using multi-task directed message-passing network (DMPNN) architectures combining uncertainty estimation, yielding an average AUC value of 0.91. Furthermore, ChemFH incorporated 1441 representative alert substructures derived from the collected data and ten commonly used frequent hitter screening rules. ChemFH was validated with an external set of 75 compounds. Subsequently, the virtual screening capability of ChemFH was successfully confirmed through its application to five virtual screening libraries. Furthermore, ChemFH underwent additional validation on two natural products and FDA-approved drugs, yielding reliable and accurate results. ChemFH is a comprehensive, reliable, and computationally efficient screening pipeline that facilitates the identification of true positive results in assays, contributing to enhanced efficiency and success rates in drug discovery. ChemFH is freely available via https://chemfh.scbdd.com/.

8.
Int J Oncol ; 64(6)2024 06.
Article in English | MEDLINE | ID: mdl-38757340

ABSTRACT

Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Ras­association domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more in­depth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.


Subject(s)
DNA Methylation , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Epigenesis, Genetic , Prognosis , MicroRNAs/genetics , Signal Transduction/genetics , Promoter Regions, Genetic
9.
J Ovarian Res ; 17(1): 105, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760835

ABSTRACT

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.


Subject(s)
Fertilization in Vitro , Infertility, Female , Ovulation Induction , Humans , Female , Infertility, Female/metabolism , Infertility, Female/blood , Adult , Ovarian Hyperstimulation Syndrome/blood , Ovarian Hyperstimulation Syndrome/metabolism , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complications , Gas Chromatography-Mass Spectrometry , Metabolome , Metabolomics/methods , Pregnancy , Ovary/metabolism
10.
Sensors (Basel) ; 24(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38733009

ABSTRACT

Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.


Subject(s)
Biosensing Techniques , Polymers , Wearable Electronic Devices , Polymers/chemistry , Humans , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Biosensing Techniques/instrumentation , Biosensing Techniques/methods
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124350, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38692108

ABSTRACT

Smartphone-based digital image colorimetry is a powerful, fast, low-cost approach to detecting target analytes. However, lighting conditions and camera parameters easily affect the detection results, significantly curtailing its applicability in multiple scenarios. In this study, an Android-based mobile application (SMP-CC) is developed, which offers a comprehensive package that includes image acquisition, color correction, and colorimetric analysis functions. Using a custom color card, a built-in algorithm in SMP-CC can minimize the color difference between the standard color block image captured by different smartphones under different lighting conditions and the standard value by an LS171 colorimeter less than 4.36. The algorithm significantly eliminates the impacts of external lighting conditions and differences in cell phone models. Furthermore, the feasibility of SMP-CC was verified by successful colorimetric detection of urine pH, glucose, and protein, demonstrating its potential in smartphone-based digital image colorimetry.

12.
Abdom Radiol (NY) ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796626

ABSTRACT

PURPOSE: To assess the safety and effectiveness of PTPBD for CBD stones in the elderly population. METHODS: Patients aged 60 years or older, who underwent PTPBD or ERCP for CBD stones between January 2021 and December 2023, were included in this study and divided into either the PTPBD group or the ERCP group based on the procedure they underwent. Baseline characteristics, intraoperative and postoperative outcomes were collected and analyzed using SPSS 25.0. RESULTS: A total of 145 cases were enrolled in the study. In terms of intraoperative complications, one patient in the ERCP group experienced hemorrhaging, while one patient in the PTPBD group experienced acute pain. However, neither of these patients were in a serious condition and only required observation. Stone removal procedures were successfully conducted in approximately 95% of cases in both the PTPBD and ERCP groups (95.8 and 94.8%, respectively; P > 0.999). ERCP failures were observed in one patient with a previous Billroth II anastomosis and two patients with unconventional anatomy of the esophagus and stomach. There was no statistically significant difference in postoperative complications between the PTPBD group and the ERCP group (P > 0.05). The length of hospital stays did not differ between the PTPBD group and the ERCP group (P = 0.537 > 0.05). CONCLUSION: PTPBD can be used in patients who have complicated anatomical issues that make the ERCP procedure difficult. In comparison, PTPBD is a similarly safe, effective, and minimally invasive technique for extracting CBD stones in elderly patients.

13.
Int J Antimicrob Agents ; : 107221, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38810938

ABSTRACT

Phage therapy has shown great promise in the treatment of bacterial infections. However, the effectiveness of phage therapy is compromised by the inevitable emergence of phage-resistant strains. In this study, a phage-resistant Carbapenem-Resistant Klebsiella pneumoniae (CRKP) strain SWKP1711R, derived from parental CRKP strain SWKP1711 was identified. The mechanism of bacteriophage resistance in SWKP1711R was investigated and the molecular determinants causing altered growth characteristics, antibiotic resistance, and virulence of SWKP1711R were tested. Compared to SWKP1711, SWKP1711R showed slower growth, smaller colonies, filamentous cells visible under the microscope, reduced production of capsular polysaccharide (CPS) and lipopolysaccharide (LPS), and reduced resistance to various antibiotics accompanied by reduced virulence. Adsorption experiments showed that phage vB_kpnM_17-11 lost the ability to adsorb onto SWKP1711R, and the adsorption receptor was identified to be bacterial surface polysaccharides. Genetic variation analysis revealed that, compared to the parental strain, SWKP1711R had only one thymine deletion at position 78 of the open reading frame of the lpcA gene, resulting in a frameshift mutation that caused alteration of the bacterial surface polysaccharide and inhibition of phage adsorption, ultimately leading to phage resistance. Transcriptome analysis and quantitative reverse transcriptase PCR (qRT-PCR) revealed that genes encoding LPS synthesis, ompK35, blaTEM-1, and type II and Hha-TomB toxin antitoxin (TA) systems, were all downregulated in SWKP1711R. Taken together, the evidence presented here indicate that the phenotypic alterations and phage resistance displayed by the mutant may be related to the frameshift mutation of lpcA and altered gene expression. While evolution of phage resistance remains an issue, our study suggests that the reduced antibiotic resistance and virulence of phage-resistant strain derivatives might be beneficial in alleviating the burden caused by multidrug-resistant bacteria.

14.
J Affect Disord ; 359: 350-355, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38801921

ABSTRACT

BACKGROUND: While existing studies have suggested an increased risk of COVID-19 in patients with depression, the causal impact of MDD on the severity of COVID-19 remains to be validated. Additionally, the potential impact of antidepressant medication on the risk of COVID-19 is not known. METHODS: In our study, we applied a Mendelian Randomization (MR) method, leveraging summary data from GWAS, to evaluate the potential causal effects of depression on three COVID-19 outcomes. Furthermore, we investigated the causal effects of antidepressants on COVID-19 outcomes. The COVID-19 datasets contain information on various stages of the disease, including SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Datasets for depression and antidepressants were comprised of 1,349,887 and 106,785 participants, respectively. RESULTS: Employing the inverse variance-weighted (IVW) method, we show a causal association between depression and three COVID-19 outcomes. Specifically, we found that genetic liability to depression is linked to critical COVID-19 (OR: 1.28, 95 % CI: 1.13-1.46), hospitalized COVID-19 (OR: 1.23, 95 % CI: 1.13-1.34), and SARS-CoV-2 infection (OR: 1.06, 95 % CI: 1.02-1.10). Interestingly, the use of antidepressants was not associated with COVID-19, with the odds ratios for critical COVID-19 (OR: 1.05, 95 % CI: 0.88-1.26), hospitalization (OR: 1.01, 95 % CI: 0.90-1.13), and SARS-CoV-2 infection (OR: 1.03, 95 % CI: 0.99-1.08) indicating no causal impact. CONCLUSION: Our study indicates that genetic liability to depression may increase the susceptibility to COVID-19 and its severe forms. The lack of causal effect of antidepressant use on COVID-19 implies antidepressant medication may counteract the detrimental effect of depression on COVID-19.

15.
Chem Sci ; 15(20): 7651-7658, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38784745

ABSTRACT

Synaptic plasticity is the ability of synapses to modulate synaptic strength in response to dynamic changes within, as well as environmental changes. Although there is a considerable body of knowledge on protein expression and receptor migration in different categories of synaptic plasticity, the contribution and impact of presynaptic vesicle release and neurotransmitter levels towards plasticity remain largely unclear. Herein, nanoelectrochemistry using carbon fiber nanoelectrodes with excellent spatio-temporal resolution was applied for real-time monitoring of presynaptic vesicle release of dopamine inside single synapses of dopaminergic neurons, and exocytotic variations in quantity and kinetics under repetitive electrical stimuli. We found that the presynaptic terminal tends to maintain synaptic strength by rapidly recruiting vesicles, changing the dynamics of exocytosis, and maintaining sufficient neurotransmitter release in following stimuli. Except for small clear synaptic vesicles, dense core vesicles are involved in exocytosis to sustain the neurotransmitter level in later periods of repetitive stimuli. These data indicate that vesicles use a potential regulatory mechanism to establish short-term plasticity, and provide new directions for exploring the synaptic mechanisms in connection and plasticity.

16.
Phys Rev Lett ; 132(19): 193601, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38804949

ABSTRACT

Coherent and dissipative interactions between different quantum systems are essential for the construction of hybrid quantum systems and the investigation of novel quantum phenomena. Here, we propose and analyze a magnon-skyrmion hybrid quantum system, consisting of a micromagnet and nearby magnetic skyrmions. We predict a strong-coupling mechanism between the magnonic mode of the micromagnet and the quantized helicity degree of freedom of the skyrmion. We show that with this hybrid setup it is possible to induce magnon-mediated nonreciprocal interactions and responses between distant skyrmion qubits or between skyrmion qubits and other quantum systems like superconducting qubits. This work provides a quantum platform for the investigation of diverse quantum effects and quantum information processing with magnetic microstructures.

17.
Article in English | MEDLINE | ID: mdl-38602173

ABSTRACT

A novel actinobacterium, strain HUAS 3T, was isolated from the rhizosphere soil of Cathaya argyrophylla collected in Hunan Province, PR China. Strain HUAS 3T contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The dominant menaquinones were MK-9(H4), MK-9(H6), MK-10(H2) and MK-9(H4). The polar lipids consisted of diphosphatidylglycerol, phospholipids, phosphatidylethanolamine, phosphatidylglycerol, phosphotidylinositol and phosphatidylinositol mannosides. The main cellular fatty acids (>5.0 %) were C17 : 1 ω8c, iso-C16 : 0, C18 : 1 ω9c, iso-C15 : 0, C16 : 0 and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c). The DNA G+C content of the novel strain's genome sequence, consisting of 7 196 442 bp, was 72.8 mol%. The full-length 16S rRNA gene sequence analysis indicated that strain HUAS 3T belonged to the genus Micromonospora and showed highest similarities to Micromonospora fluminis A38T (99.44 %), Micromonospora echinospora DSM 43816T (99.23 %), Micromonospora tulbaghiae DSM 45142T (99.23 %), Micromonospora solifontis PPF5-17T (99.16 %) and Micromonospora endolithica DSM 44398T (98.96 %). Phylogenetic trees based on 16S rRNA gene sequences showed that strain HUAS 3T was closely related to M. fluminis A38T, M. tulbaghiae DSM 45142T and M. solifontis PPF5-17T. The phylogenomic tree revealed that strain HUAS 3T was closely related to Micromonospora pallida DSM 43817T. However, the average nucleotide identity (ANIb/ANIm) and the digital DNA-DNA hybridization values between them were 84.75 /88.16 and 30.80 %, respectively, far less than the 95-96 and 70 % cut-off points recommended for delineating species. Furthermore, strain HUAS 3T was distinct from the type strain of M. pallida in terms of phenotypic and chemotaxonomic characteristics. In summary, strain HUAS 3T represents a novel Micromonospora species, for which the name Micromonospora cathayae sp. nov. is proposed. The type strain is HUAS 3T (=MCCC 1K08599T=JCM 36275T).


Subject(s)
Fatty Acids , Micromonospora , Fatty Acids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , Rhizosphere , Sequence Analysis, DNA , DNA, Bacterial/genetics , Base Composition , Bacterial Typing Techniques
18.
Small ; : e2310064, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607265

ABSTRACT

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*O→*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.

19.
Biol Reprod ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647664

ABSTRACT

OBJECTIVE: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. METHODS: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role. RESULTS: Our findings indicate that HMGB1flox/floxElf5cre/+ mouse display fetal growth restriction (FGR), characterized by decreased placental and fetal weight and impaired bone development. And the absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. CONCLUSIONS: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.

20.
Huan Jing Ke Xue ; 45(5): 3069-3077, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629567

ABSTRACT

Microplastic pollution in the soil environment has received extensive attention, but the effects of different land use patterns on the sub-watershed scale on soil microplastic pollution are poorly understood. The Luoshijiang sub-watershed in the north of Erhai Lake was selected as the research object, and the characteristics of microplastic pollution in farmland, riparian zone, grassland, and woodland soils were analyzed. The pollution risks of microplastics in the four types of soil were assessed using the polymer risk index method, and the effects of land use patterns on the distribution and risk of microplastic pollution were further explored. The results showed that:① The abundance of microplastics in the soil of the Luoshijiang sub-watershed ranged from 220 to 1 900 n·kg-1, and the average abundance was (711 ± 55) n·kg-1. The main polymer types were polyester (PES, 32.52%) and polyethylene terephthalate (PET, 21.95%). The particle size of microplastics was concentrated in the range of 0.5-2 mm (61.89%). Fiber was the main shape of microplastics (>75%), and the dominant color was transparent (58.50%). ② Land use patterns determined the abundance and pollution characteristics of soil microplastics in the Luoshijiang sub-watershed. A significantly higher abundance of microplastics was found in the soil of farmland[(885 ± 95) n·kg-1] and riparian zone[(837 ± 155) n·kg-1], which had stronger intensities of human activity, than that in woodland soil[(491 ± 53) n·kg-1] (P<0.05). Film and fragment microplastics mainly occurred in farmland soil, which also had the largest number of polymer types and the most abundant colors. ③ The risk index level of microplastics (Level Ⅲ) in the soil of farmland was higher than that of the other three land use patterns (Level Ⅰ). This research indicated that the higher the intensity of human activities of a sub-watershed was, the more complex the occurrence characteristics of soil microplastics, the richer the types of polymers, and the higher the potential pollution risks would be. Therefore, it is necessary to strengthen the control of soil microplastic pollution in farmland.

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