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2.
J Colloid Interface Sci ; 670: 61-72, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38759269

ABSTRACT

Lithium-sulfur batteries (LSBs) hold great potential as future energy storage technology, but their widespread application is hampered by the slow polysulfide conversion kinetics and the sulfur loss during cycling. In this study, we detail a one-step approach to growing tungsten phosphide (WP) nanoparticles on the surface of nitrogen and phosphorus co-doped carbon nanosheets (WP@NPC). We further demonstrate that this material provides outstanding performance as a multifunctional separator in LSBs, enabling higher sulfur utilization and exceptional rate performance. These excellent properties are associated with the abundance of lithium polysulfide (LiPS) adsorption and catalytic conversion sites and rapid ion transport capabilities. Experimental data and density functional theory calculations demonstrate tungsten to have a sulfophilic character while nitrogen and phosphorus provide lithiophilic sites that prevent the loss of LiPSs. Furthermore, WP regulates the LiPS catalytic conversion, accelerating the Li-S redox kinetics. As a result, LSBs containing a polypropylene separator coated with a WP@NPC layer show capacities close to 1500 mAh/g at 0.1C and coulombic efficiencies above 99.5 % at 3C. Batteries with high sulfur loading, 4.9 mg cm-2, are further produced to validate their superior cycling stability. Overall, this work demonstrates the use of multifunctional separators as an effective strategy to promote LSB performance.

3.
PLoS One ; 19(5): e0295350, 2024.
Article in English | MEDLINE | ID: mdl-38748674

ABSTRACT

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.


Subject(s)
Talus , Humans , Male , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Female , Adult , Bone Screws , Ankle Fractures/surgery , Ankle Fractures/diagnostic imaging
4.
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.

5.
J Ethnopharmacol ; 331: 118279, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38705425

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown. AIM OF THE STUDY: The present study was designed to investigate the effect and mechanism of flavonoid luteolin and its analog luteolin-7-methylether contained in L. japonicus on aromatase, a rate-limiting enzyme that catalyzes the conversion of androgens to estrogens and a drug target to induce ovulation in PCOS patients. MATERIALS AND METHODS: Estrogen biosynthesis in human ovarian granulosa cells was examined using ELISA. Western blots were used to explore the signaling pathways in the regulation of aromatase expression. Transcriptomic analysis was conducted to elucidate the potential mechanisms of action of compounds. Finally, animal models were used to assess the therapeutic potential of these compounds in PCOS. RESULTS: Luteolin potently inhibited estrogen biosynthesis in human ovarian granulosa cells stimulated by follicle-stimulating hormone. This effect was achieved by decreasing cAMP response element-binding protein (CREB)-mediated expression of aromatase. Mechanistically, luteolin and luteolin-7-methylether targeted tumor progression locus 2 (TPL2) to suppress mitogen-activated protein kinase 3/6 (MKK3/6)-p38 MAPK-CREB pathway signaling. Transcriptional analysis showed that these compounds regulated the expression of different genes, with the MAPK signaling pathway being the most significantly affected. Furthermore, luteolin and luteolin-7-methylether effectively alleviated the symptoms of PCOS in mice. CONCLUSIONS: This study demonstrates a previously unrecognized role of TPL2 in estrogen biosynthesis and suggests that luteolin and luteolin-7-methylether have potential as novel therapeutic agents for the treatment of PCOS. The results provide a foundation for further development of these compounds as effective and safe therapies for women with PCOS.


Subject(s)
Aromatase , Estrogens , Granulosa Cells , Leonurus , Luteolin , Polycystic Ovary Syndrome , Female , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/metabolism , Luteolin/pharmacology , Luteolin/isolation & purification , Animals , Humans , Aromatase/metabolism , Aromatase/genetics , Leonurus/chemistry , Estrogens/pharmacology , Estrogens/biosynthesis , Mice , Granulosa Cells/drug effects , Granulosa Cells/metabolism , Aromatase Inhibitors/pharmacology , Aromatase Inhibitors/isolation & purification
6.
Anal Bioanal Chem ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38802680

ABSTRACT

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

7.
J Geriatr Cardiol ; 21(4): 421-430, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38800549

ABSTRACT

BACKGROUND: Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) are available. METHODS: We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months (interquartile range: 26-73 months) follow-up period were compared between patients with the low prealbumin level (< 170 mg/L) and those with the high prealbumin level (≥ 170 mg/L). RESULTS: A total of 114 patients (4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class III (9.9% vs. 4.4%, P = 0.034), cardiovascular death (8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events (19.2% vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level (< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events (odds ratio = 1.918, 95% CI: 1.250-2.942, P = 0.003). The cut-off value of prealbumin level for predicting in-hospital death was 170 mg/L (area under the curve = 0.703, 95% CI: 0.651-0.754, P < 0.001; sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level (170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results. CONCLUSIONS: Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients.

8.
Phytochemistry ; 222: 114098, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38648960

ABSTRACT

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.


Subject(s)
Amyloid beta-Peptides , Apoptosis , Microglia , Molecular Docking Simulation , Peptide Fragments , Microglia/drug effects , Microglia/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Peptide Fragments/pharmacology , Animals , Apoptosis/drug effects , Mice , Molecular Structure , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Dose-Response Relationship, Drug , Lentinula/chemistry , Cell Line
9.
Environ Int ; 187: 108688, 2024 May.
Article in English | MEDLINE | ID: mdl-38685158

ABSTRACT

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere microbiome and functional genes in various microhabitats (i.e., leaf litter, moss and plant leaves) across the succession of a plant community in a low-altitude glacier foreland. Our findings indicate that phyllosphere microbiomes and associated ecosystem stability increase during the succession of the plant community. The abundance of core taxa increased with plant community succession and was primarily governed by deterministic processes. In contrast, satellite taxa abundance decreased during plant community succession and was mainly governed by stochastic processes. The abundance of microbial functional genes (such as C, N, and P hydrolysis and fixation) in plant leaves generally increased during the plant community succession. However, in leaf litter and moss leaves, only a subset of functional genes (e.g., C fixation and degradation, and P mineralization) showed a tendency to increase with plant community succession. Ultimately, the community of both core and satellite taxa collaboratively influenced the characteristics of phyllosphere nutrient-cycling genes, leading to the diverse profiles and fluctuating abundance of various functional genes during plant community succession. These findings offer valuable insights into the phyllosphere microbiome and plant-microbe interactions during plant community development, advancing our understanding of the succession and functional significance of the phyllosphere microbial community.


Subject(s)
Microbiota , Plant Leaves , Plant Leaves/microbiology , Ecosystem , Plants/microbiology , Plant Development
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 588-594, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660871

ABSTRACT

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.


Subject(s)
CD56 Antigen , Dendritic Cells , Aged , Humans , Male , CD4 Antigens/metabolism , CD56 Antigen/metabolism , Hematologic Neoplasms , Immunophenotyping , Prognosis , Retrospective Studies
11.
Foods ; 13(8)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38672858

ABSTRACT

Lactobacillus fermentum (L. fermentum) was first evaluated as a potential advanced glycation end-product (AGE) formation inhibitor by establishing a bovine serum albumin (BSA) + glucose (glu) glycation model in the present study. The results showed that the highest inhibition rates of pentosidine and total fluorescent AGEs by L. fermentum were approximately 51.67% and 77.22%, respectively, which were higher than that of aminoguanidine (AG). Mechanistic analysis showed that L. fermentum could capture methylglyoxal and glyoxal, inhibit carbonyl and sulfhydryl oxidation, reduce the binding of glucose and amino groups, increase total phenolic content and antioxidant activity, and release intracellular substances to scavenge free radicals; these abilities were the basis of the antiglycation mechanism of L. fermentum. In addition, L. fermentum significantly prevented conformational changes in proteins during glycation, reduced protein cross-linking by 35.67%, and protected the intrinsic fluorophore. Therefore, the inhibition of L. fermentum on glycation mainly occurs through antioxidation, the capture of dicarbonyl compounds, and the protection of the BSA structure. These findings collectively suggest that Lactobacillus is an inhibitor of protein glycation and AGE formation and has the potential for nutraceutical applications.

12.
Int J Mol Sci ; 25(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38673840

ABSTRACT

Sea cucumbers are widely known for their powerful regenerative abilities, which allow them to regenerate a complete digestive tract within a relatively short time following injury or autotomy. Recently, even though the histological changes and cellular events in the processes of intestinal regeneration have been extensively studied, the molecular machinery behind this faculty remains unclear. In this study, tandem mass tag (TMT)-based quantitation was utilized to investigate protein abundance changes during the process of intestine regeneration. Approximately 538, 445, 397, 1012, and 966 differential proteins (DEPs) were detected (p < 0.05) between the normal and 2, 7, 12, 20, and 28 dpe stages, respectively. These DEPs also mainly focus on pathways of cell proliferation and apoptosis, which were further validated by 5-Ethynyl-2'-deoxyuridine (EdU) or Tunel-based flow cytometry assay. These findings provide a reference for a comprehensive understanding of the regulatory mechanisms of various stages of intestinal regeneration and provide a foundation for subsequent research on changes in cell fate in echinoderms.


Subject(s)
Apoptosis , Cell Proliferation , Intestines , Proteomics , Regeneration , Animals , Proteomics/methods , Intestines/physiology , Intestines/cytology , Stichopus/metabolism , Stichopus/physiology , Tandem Mass Spectrometry , Proteome/metabolism
14.
Fitoterapia ; 175: 105960, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38621426

ABSTRACT

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.


Subject(s)
Phytochemicals , Plant Roots , Rehmannia , Plant Roots/chemistry , Molecular Structure , Rehmannia/chemistry , Humans , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Sesquiterpenes/chemistry , Apoptosis/drug effects , Cell Line , Reactive Oxygen Species/metabolism , China , Polycyclic Sesquiterpenes/pharmacology , Polycyclic Sesquiterpenes/isolation & purification , Polycyclic Sesquiterpenes/chemistry
15.
Cell Mol Life Sci ; 81(1): 196, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658440

ABSTRACT

Telomeres as the protective ends of linear chromosomes, are synthesized by the enzyme telomerase (TERT). Critically short telomeres essentially contribute to aging-related diseases and are associated with a broad spectrum of disorders known as telomeropathies. In cardiomyocytes, telomere length is strongly correlated with cardiomyopathies but it remains ambiguous whether short telomeres are the cause or the result of the disease. In this study, we employed an inducible CRISPRi human induced pluripotent stem cell (hiPSC) line to silence TERT expression enabling the generation of hiPSCs and hiPSC-derived cardiomyocytes with long and short telomeres. Reduced telomerase activity and shorter telomere lengths of hiPSCs induced global transcriptomic changes associated with cardiac developmental pathways. Consequently, the differentiation potential towards cardiomyocytes was strongly impaired and single cell RNA sequencing revealed a shift towards a more smooth muscle cell like identity in the cells with the shortest telomeres. Poor cardiomyocyte function and increased sensitivity to stress directly correlated with the extent of telomere shortening. Collectively our data demonstrates a TERT dependent cardiomyogenic differentiation defect, highlighting the CRISPRi TERT hiPSCs model as a powerful platform to study the mechanisms and consequences of short telomeres in the heart and also in the context of telomeropathies.


Subject(s)
Cell Differentiation , Induced Pluripotent Stem Cells , Myocytes, Cardiac , Telomerase , Telomere , Telomerase/metabolism , Telomerase/genetics , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/cytology , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Telomere/metabolism , Telomere Shortening , Cell Line
16.
Chem Biodivers ; : e202400635, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687253

ABSTRACT

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6″-galloyl-glucopyranoside) (2a), along with six known flavonoid glycosides (2b - 7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1 - 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2a, 2b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2a, 2b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

17.
Postgrad Med J ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656404

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

18.
Int J Mol Sci ; 25(8)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38674009

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection. Using bioinformatics, biochemical, and biological assays, we provide evidence for the presence of G4 structures in the promoter regions of SARS-CoV-2 host factors NRP1. Specifically, we focus on two representative G4s in the NRP1 promoter and highlight its importance in SARS-CoV-2 pathogenesis. The presence of the G4 structure greatly increases NRP1 expression, facilitating SARS-CoV-2 entry into cells. Utilizing published single-cell RNA sequencing data obtained from simulated SARS-CoV-2 infection in human bronchial epithelial cells (HBECs), we found that ciliated cells with high levels of NRP1 are prominently targeted by the virus during infection. Furthermore, our study identifies E2F1 act as a transcription factor that binds to G4s. These findings uncover a previously unknown mechanism underlying SARS-CoV-2 infection and suggest that targeting G4 structures could be a potential strategy for COVID-19 prevention and treatment.


Subject(s)
COVID-19 , G-Quadruplexes , Neuropilin-1 , Promoter Regions, Genetic , Humans , COVID-19/genetics , COVID-19/virology , E2F1 Transcription Factor/metabolism , E2F1 Transcription Factor/genetics , Epithelial Cells/virology , Epithelial Cells/metabolism , Neuropilin-1/genetics , Neuropilin-1/metabolism , SARS-CoV-2/physiology , Virus Internalization
19.
J Diabetes ; 16(4): e13530, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38584151

ABSTRACT

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Fractures, Bone , Male , Humans , Female , Bone Density , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Cross-Sectional Studies , Retrospective Studies , Prevalence , Absorptiometry, Photon , Fractures, Bone/etiology , Fractures, Bone/complications
20.
Cereb Cortex ; 34(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38602740

ABSTRACT

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.


Subject(s)
Executive Function , Exercise , Humans , Memory, Short-Term , Cerebrovascular Circulation , Dorsolateral Prefrontal Cortex
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