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1.
Nutrients ; 16(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38732537

ABSTRACT

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.


Subject(s)
Endocrine Disruptors , Phthalic Acids , Sleep , Vitamin D Deficiency , Vitamin D , Humans , Endocrine Disruptors/adverse effects , Vitamin D Deficiency/epidemiology , Female , Male , United States/epidemiology , Adult , Phthalic Acids/adverse effects , Middle Aged , Sleep/drug effects , Vitamin D/blood , Phenols/adverse effects , Environmental Exposure/adverse effects , Benzhydryl Compounds/adverse effects , Nutrition Surveys , Triclosan/adverse effects , Aged , Young Adult
2.
Front Public Health ; 12: 1376404, 2024.
Article in English | MEDLINE | ID: mdl-38651131

ABSTRACT

Background: Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults. Methods: All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China's TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored. Results: From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05-1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28-2.26), passive case finding (AOR: 1.46, 95% CI: 1.07-1.98) and retreatment (AOR: 1.52, 95% CI: 1.11-2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53-0.90) and non-students (AOR: 0.83, 95% CI: 0.71-0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29-1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32-1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30-1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78-1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59-0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before. Conclusion: In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.


Subject(s)
COVID-19 , Tuberculosis, Pulmonary , Humans , Adolescent , Female , China/epidemiology , Male , Young Adult , COVID-19/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adult , Time-to-Treatment/statistics & numerical data , Delayed Diagnosis/statistics & numerical data , Tuberculosis/epidemiology , Logistic Models , SARS-CoV-2
3.
Nature ; 628(8009): 910-918, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38570680

ABSTRACT

OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.


Subject(s)
Calcium Channels , Cryoelectron Microscopy , Ion Channel Gating , Mechanotransduction, Cellular , Humans , Anoctamins/chemistry , Anoctamins/metabolism , Calcium Channels/chemistry , Calcium Channels/metabolism , Calcium Channels/ultrastructure , Lipids/chemistry , Liposomes/metabolism , Liposomes/chemistry , Models, Molecular , Nanostructures/chemistry
4.
Metabolites ; 14(3)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38535299

ABSTRACT

Herein, we explored the overall association between metal mixtures and lung functions in populations of varying ages and the relationship among the associated components. The 2007-2012 National Health and Nutrition Examination Survey data of 4382 American participants was analyzed, and generalized linear, elastic net, quantile g-computation, and Bayesian kernel machine regression models were used to evaluate the relationship between exposure to the metal mixture and lung function at various ages. The results of barium exposure at distinct stages revealed that children and adolescents exhibited greater lung function changes than those in adults and the elderly. Additionally, compared with children and adolescents, cadmium- and arsenic-containing metabolites contributed to nonconductive lung function changes in adults and the elderly exposed to metal mixtures. The results showed that the effects of exposure to metal mixtures on lung function in children and adolescents were predominantly caused by lead and barium. Altogether, children and adolescents were found to be more susceptible to metal-exposure-mediated lung function changes than adults and the elderly.

5.
Nat Cell Biol ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538834

ABSTRACT

Gasdermin D (GSDMD) is the executor of pyroptosis, which is important for host defence against pathogen infection. Following activation, caspase-mediated cleavage of GSDMD releases an amino-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and release of proinflammatory cytokines. The spatial and temporal regulation of this process in cells remains unclear. Here we identify GSDMD as a substrate for reversible S-palmitoylation on C192 during pyroptosis. The palmitoyl acyltransferase DHHC7 palmitoylates GSDMD to direct its cleavage by caspases. Subsequently, palmitoylation of GSDMD-NT promotes its translocation to the plasma membrane, where APT2 depalmitoylates GSDMD-NT to unmask the C192 residue and promote GSDMD-NT oligomerization. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, leading to increased survival of mice with lipopolysaccharide-induced lethal septic shock and increased sensitivity to bacterial infection. Our findings reveal a model through which a palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation during pyroptosis.

6.
Cell Rep ; 43(3): 113827, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38381607

ABSTRACT

Nuclear speckles (NSs) are nuclear biomolecular condensates that are postulated to form by macromolecular phase separation, although the detailed underlying forces driving NS formation remain elusive. SRRM2 and SON are 2 non-redundant scaffold proteins for NSs. How each individual protein governs assembly of the NS protein network and the functional relationship between SRRM2 and SON are largely unknown. Here, we uncover immiscible multiphases of SRRM2 and SON within NSs. SRRM2 and SON are functionally independent, specifically regulating alternative splicing of subsets of mRNA targets, respectively. We further show that SRRM2 forms multicomponent liquid phases in cells to drive NS subcompartmentalization, which is reliant on homotypic interaction and heterotypic non-selective protein-RNA complex coacervation-driven phase separation. SRRM2 serine/arginine-rich (RS) domains form higher-order oligomers and can be replaced by oligomerizable synthetic modules. The serine residues within the RS domains, however, play an irreplaceable role in fine-tuning the liquidity of NSs.


Subject(s)
Nuclear Speckles , RNA-Binding Proteins , RNA-Binding Proteins/metabolism , Phase Separation , Alternative Splicing/genetics , Serine/metabolism
7.
Front Plant Sci ; 15: 1287379, 2024.
Article in English | MEDLINE | ID: mdl-38384751

ABSTRACT

Trifolium repens L. (white clover) and Lolium perenne L. (ryegrass) are green manures widely used in conservation tillage systems worldwide. Eleusine indica L. (goosegrass) is a globally recognized noxious weed. Herein, we investigated the effects of aqueous extracts, decomposed liquids, and different straw-to-soil ratios on the germination and growth of goosegrass. The results showed that high concentrations (≥ 30%) of aqueous extracts or decomposed liquids of both green manures significantly inhibited germination-related parameters of goosegrass. The strongest inhibitory effect was observed for the 7-day decomposition treatment, and white clover's inhibitory effect was greater than ryegrass's. A pot experiment showed that non-photochemical quenching, catalase, and peroxidase activity levels of goosegrass leaves were significantly increased. At the same time, the net photosynthetic rate significantly decreased. Seedling growth was inhibited when the straw-to-soil ratio was greater than 3:100. The ryegrass treatments inhibited goosegrass seedlings more than the white clover treatments. This study demonstrated the inhibitory potential of white clover and ryegrass straw return on seed germination and seedling growth of goosegrass. The study has also helped to identify weed-resistant substances in these green manures so that their weed-control properties can be used more effectively and herbicide usage can be reduced.

8.
Foodborne Pathog Dis ; 20(10): 467-476, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37699240

ABSTRACT

Salmonella is a primary cause of foodborne diseases, and the increasing prevalence of mcr-1-carrying plasmids, which confer colistin resistance to Salmonella, poses significant global health concerns. As the frequency of occurrence of the mcr-1 gene is increasing globally, we studied the prevalence of mcr-1 in clinical Salmonella isolates by analyzing 195 clinical strains isolated in 2020. Of the 195 Salmonella isolates, 41 isolates were resistant to colistin. We found mcr-1 in two strains (Salmonella Typhimurium ZJJX20006 and Salmonella Kentucky ZJJX20014), which we analyzed in detail via whole-genome sequencing and antibiotic susceptibility testing. Two strains displayed resistance to ampicillin, ampicillin-sulbactam, tetracycline, chloramphenicol, and cotrimoxazole, while ZJJX20006 displayed resistance to colistin and ZJJX20014 was sensitive. Genomic analysis revealed that these strains had plasmid-encoded mcr-1 in IncHI2 plasmids, which were not similar to the mcr-1-IncX4 identified in 2016. These two strains also harbored other drug resistance genes, including blaOXA-1 and blaCTX-M-14. Our findings may help clarify the molecular mechanisms of mcr-1 dissemination among Salmonella strains in Jiaxing City and offer insights into the evolution of mcr-1 in Salmonella.

9.
Healthcare (Basel) ; 11(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36900748

ABSTRACT

Influential existing research has suggested that rather than being static, mortality declines decelerate at young ages and accelerate at old ages. Without accounting for this feature, the forecast mortality rates of the popular Lee-Carter (LC) model are less reliable in the long run. To provide more accurate mortality forecasting, we introduce a time-varying coefficients extension of the LC model by adopting the effective kernel methods. With two frequently used kernel functions, Epanechnikov (LC-E) and Gaussian (LC-G), we demonstrate that the proposed extension is easy to implement, incorporates the rotating patterns of mortality decline and is straightforwardly extensible to multi-population cases. Using a large sample of 15 countries over 1950-2019, we show that LC-E and LC-G, as well as their multi-population counterparts, can consistently improve the forecasting accuracy of the competing LC and Li-Lee models in both single- and multi-population scenarios.

10.
Methods Mol Biol ; 2600: 283-289, 2023.
Article in English | MEDLINE | ID: mdl-36587104

ABSTRACT

The ligand-receptor complexes in the cell-cell and cell-ECM interfaces mediate the mechanical coupling of cells to their microenvironment and transduce downstream signals to modulate cell functions. In this chapter I describe a microfabrication strategy to prepare a substrate of spatially segregated supported lipid bilayers and ECM components on which cells can form juxtacrine receptor signaling complexes and integrin adhesions simultaneously. This platform is specifically applicable for microscopically monitoring the signal transduction of each receptor, as well as the modulatory effects of receptor signaling on integrin adhesions and cell behaviors.


Subject(s)
Lipid Bilayers , Signal Transduction , Lipid Bilayers/chemistry , Cell Adhesion/physiology , Signal Transduction/physiology , Cell Membrane/metabolism , Integrins/metabolism
11.
Journal of Preventive Medicine ; (12): 316-319, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-971791

ABSTRACT

Objective@#To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. @*Methods@#According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. @*Results@#The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. @*Conclusion@#This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

12.
Front Plant Sci ; 13: 1013443, 2022.
Article in English | MEDLINE | ID: mdl-36466260

ABSTRACT

Astragalus sinicus L. (milk vetch), a versatile plant that has a soil-enriching effect as green manure, is widely planted in the temperate zone of China. In previous experiments, milk vetch incorporated into the soil as green manure showed potential for goosegrass control. However, "what exactly happens at the chemical level?" and "what are the compounds that are potentially responsible for the phytotoxic effects observed during those previous assays?" In a recent study, in vitro phytotoxicity bioassays and chemical analyses of milk vetch decomposition leachates were carried out to explore the relationship between the temporal phytotoxic effects and the dynamics of chemical composition. For that, milk vetch decomposition leachates with a decay time of 12 h, 9 days, 12 days, 15 days, and 18 days were analyzed for organic compounds by liquid chromatography. The main results were as follows: (1) three compounds with goosegrass suppression potential produced during the decomposed process, i.e., 4-ethylphenol, N-acrylimorpholine, and allyl isothiocyanate. 2-Hydroxyethyl acrylate was present in the 12-h decomposition leachates but was at its highest concentration of 127.1 µg ml-1 at 15 days. (2) The cultures were configured according to the four concentrations of goosegrass-resistant active substances measured in the 15-day decomposition leachate and, as with the 15-day decomposition leachate, the mixture cultures inhibited 100% of goosegrass germination at the high concentrations (≥ 30%), which suggests that these substances have goosegrass suppression potential. (3) The high total phenolic content (302.8-532.3 mg L-1), the total flavonoid content (8.4-72.1 mg L-1), and the reducing activity of the decomposition leachates for different decay times may explain why the incorporation of milk vetch into the soil did not lead to peroxidation of goosegrass in the previous study. (4) Finally, the changes in acid fraction and total content (1.9-4.2 mg ml-1) for different decay times explain the variations in pH of the decomposition leachates, which, when discussed in conjunction with previous studies, may lead to changes in soil nutrient effectiveness and consequently affect crop growth. This study can provide a reference for green weed control research.

13.
Pathogens ; 11(8)2022 Jul 30.
Article in English | MEDLINE | ID: mdl-36014986

ABSTRACT

Molecular diagnostic assays for cholera detection have superior sensitivity to conventional assays and are now being accepted as the new standard method, especially the real-time PCR/RT-PCR. However, limited throughput capacity and long detection duration prevent them from detecting more specimens and more targets in one turnaround time simultaneously. In this study, we utilized nucleic acid extraction-free, direct RT-PCR and high-speed amplification to develop a novel multiplex assay, a quadplex direct one-tube real-time RT-PCR assay, for rapid detection of the serogroup and cholera toxin toxigenicity of Vibrio cholerae targeting the epsM, ctxA, rfb-O1, and rfb-O139 genes. Performance of the multiplex assay was evaluated by comparison with the monoplex real-time PCR assay according to the China Cholera Prevention Manual. Detection data from clinical specimens showed that the new assay had good diagnostic sensitivities for epsM (100%, n = 301), ctxA (100%, n = 125), rfb-O1 (100%, n = 85), and rfb-O139 (97.87%, n = 49). Analysis of the analytical sensitivities with serial dilutions of positive standards showed that the detection limits of the new assay for Vibrio cholerae epsM,ctxA,rfb-O1, and rfb-O139 were up to 200, 590, 115, and 1052 copies per mL lower than the monoplex real-time PCR (910, 345, and 1616 copies/mL respectively, for ctxA,rfb-O1, and rfb-O139). The results indicate that the multiplex assay is a rapid, sensitive, specific, and easy-to-use detection tool for Vibrio cholerae, especially suitable for rapid identification and screening detection of mass specimens.

14.
Bio Protoc ; 12(11): e4434, 2022 Jun 05.
Article in English | MEDLINE | ID: mdl-35799902

ABSTRACT

A multitude of membrane-localized receptors are utilized by cells to integrate both biochemical and physical signals from their microenvironment. The clustering of membrane receptors is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we describe a method to fabricate multicomponent, ligand-functionalized microarrays, for spatially segregated and simultaneous monitoring of receptor activation and signaling in individual living cells. While existing micropatterning techniques allow for the display of fixed ligands, this protocol uniquely allows for functionalization of both mobile membrane corrals and immobile polymers with selective ligands, as well as microscopic monitoring of cognate receptor activation at the cell membrane interface. This protocol has been developed to study the effects of clustering on EphA2 signaling transduction. It is potentially applicable to multiple cell signaling systems, or microbe/host interactions. Graphical abstract: A side-by-side comparison of clustered or non-clustered EphA2 receptor signaling in a single cell.

15.
Front Plant Sci ; 13: 829421, 2022.
Article in English | MEDLINE | ID: mdl-35574090

ABSTRACT

Astragalus sinicus L. (milk vetch), one of the most widespread green manure species, is widely planted in the temperate zone. Eleusine indica L. (goosegrass), a serious annual weed in the world, has evolved resistance to some non-selective herbicides. The use of milk vetch as green manure for weed control in paddy fields was proposed. Aqueous extracts of milk vetch are known to exert a different level of phytotoxicity on weeds and crops. Phytotoxic substances contained in green manure were released into the soil by leaching at the initial stage and decomposition at the later stage after the return of green manure. Considering the need for searching new sustainable strategies for weed control, a question arises: "if milk vetch could be applied in goosegrass control, which stage is the most important to control goosegrass after milk vetch returned to the field, and at the same time, will the subsequent crop, corn (Zea mays L.), be affected by the side effects from milk vetch phytotoxicity?" In this study, the potential of milk vetch for goosegrass control was approached by repeated laboratory experiments, which include the aqueous extract experiment, decomposed experiment, and pot experiment. The effects of milk vetch returning to the field on maize were simulated by a pot experiment. The extract of milk vetch could significantly inhibit the germination of goosegrass at 2% concentration, and the inhibition enhanced with the increase of concentration. In the decomposed liquid experiment, decay time within 15 days, with the increase of decay days or concentration, goosegrass inhibition effect of decomposed liquid was enhanced. When decay time was more than 15 days, the inhibition ability of the decomposed liquid to goosegrass decreased. According to the RI accumulated value, aqueous extract and decomposed liquid have a "hormesis effect" on the germination and growth of goosegrass. Pot experiment proved that the addition of 1-10% (w/w) of milk vetch significantly reduced the germination and growth of goosegrass. On the contrary, the comprehensive analysis showed that the participation of milk vetch was conducive to the growth of corn. Our results constitute evidence that the incorporation of milk vetch into the soil could be a feasible practice to reduce weed infarctions in the corn-based cropping system.

16.
Biophys J ; 121(10): 1897-1908, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35430415

ABSTRACT

Cells sense a variety of extracellular growth factors and signaling molecules through numerous distinct receptor tyrosine kinases (RTKs) on the cell surface. In many cases, the same intracellular signaling molecules interact with more than one type of RTK. How signals from different RTKs retain the identity of the triggering receptor and how (or if) different receptors may synergize or compete remain largely unknown. Here we utilize an experimental strategy, combining microscale patterning and single-molecule imaging, to measure the competition between ephrin-A1:EphA2 and epidermal growth factor (EGF):EGF receptor (EGFR) ligand-receptor complexes for the shared downstream signaling molecules, Grb2 and SOS. The results reveal a distinct hierarchy, in which newly formed EGF:EGFR complexes outcompete ephrin-A1:EphA2 for Grb2 and SOS, revealing a type of negative crosstalk interaction fundamentally controlled by chemical mass action and protein copy number limitations.


Subject(s)
Ephrin-A1 , Receptor, EphA2 , Epidermal Growth Factor , ErbB Receptors/metabolism , Feedback , Receptor, EphA2/metabolism , Signal Transduction
17.
Arterioscler Thromb Vasc Biol ; 42(6): 772-788, 2022 06.
Article in English | MEDLINE | ID: mdl-35477278

ABSTRACT

BACKGROUND: Arteriogenesis plays a critical role in maintaining adequate tissue blood supply and is related to a favorable prognosis in arterial occlusive diseases. Strategies aimed at promoting arteriogenesis have thus far not been successful because the factors involved in arteriogenesis remain incompletely understood. Previous studies suggest that evolutionarily conserved KANK4 (KN motif and ankyrin repeat domain-containing proteins 4) might involve in vertebrate vessel development. However, how the KANK4 regulates vessel function remains unknown. We aim to determine the role of endothelial cell-specifically expressed KANK4 in arteriogenesis. METHODS: The role of KANK4 in regulating arteriogenesis was evaluated using Kank4-/- and KANK4iECOE mice. Molecular mechanisms underlying KANK4-potentiated arteriogenesis were investigated by employing RNA transcriptomic profiling and mass spectrometry analysis. RESULTS: By analyzing Kank4-EGFP reporter mice, we showed that KANK4 was specifically expressed in endothelial cells. In particular, KANK4 displayed a dynamic expression pattern from being ubiquitously expressed in all endothelial cells of the developing vasculature to being explicitly expressed in the endothelial cells of arterioles and arteries in matured vessels. In vitro microfluidic chip-based vascular morphology analysis and in vivo hindlimb ischemia assays using Kank4-/- and KANK4iECOE mice demonstrated that deletion of KANK4 impaired collateral artery growth and the recovery of blood perfusion, whereas KANK4 overexpression leads to increased vessel caliber and blood perfusion. Bulk RNA sequencing and Co-immunoprecipitation/mass spectrometry (Co-IP/MS) analysis identified that KANK4 promoted EC proliferation and collateral artery remodeling through coupling VEGFR2 (vascular endothelial growth factor receptor 2) to TALIN-1, which augmented the activation of the VEGFR2 signaling cascade. CONCLUSIONS: This study reveals a novel role for KANK4 in arteriogenesis in response to ischemia. KANK4 links VEGFR2 to TALIN-1, resulting in enhanced VEGFR2 activation and increased EC proliferation, highlighting that KANK4 is a potential therapeutic target for promoting arteriogenesis for arterial occlusive diseases.


Subject(s)
Arterial Occlusive Diseases , Neovascularization, Physiologic , Animals , Arterial Occlusive Diseases/metabolism , Collateral Circulation , Disease Models, Animal , Endothelial Cells/metabolism , Hindlimb/blood supply , Ischemia , Mice , Mice, Knockout , Muscle, Skeletal/blood supply , Regional Blood Flow , Talin , Vascular Endothelial Growth Factor A/metabolism
18.
J Fluoresc ; 32(2): 707-713, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35044573

ABSTRACT

This study was to develop a multiplex fluorescent PCR for Shigella detection and species identification. Five primer pairs for Shigella detection and species identification were designed by Primer Premier 5.0. The multiplex fluorescent PCR was optimized by varying single parameter while other parameters were maintained. The multiplex fluorescent PCR assay could correctly detect Shigella and identify four Shigella species with a detection limits of 10 pg genomic DNA per reaction. Testing different strains and clinical samples confirmed the sensitivity and specificity of the multiplex fluorescent PCR. The newly developed multiplex fluorescent PCR assay is simple, sensitive and specific for Shigella detection and species identification. It has a potential to be used in routine Shigella detection and species identification in clinical laboratories.


Subject(s)
Fluorescence , Multiplex Polymerase Chain Reaction/methods , Shigella/classification , Shigella/isolation & purification , Genes, Bacterial , Humans , Sensitivity and Specificity , Shigella/genetics
19.
Front Psychol ; 13: 1084963, 2022.
Article in English | MEDLINE | ID: mdl-36698565

ABSTRACT

The present study sifts the indirect role of psychological capital (PsyCap) in linking authentic leadership (AL) and job performance (JP). Furthermore, this study investigates the interplay of AL and perceived organizational support (POS) in PsyCap. We tested these assumptions through PROCESS macro with two sources of data collected from 350 employees and their respective colleagues working in education sector organizations in China. The study findings established that AL positively influences employee performance directly and indirectly through PsyCap. POS moderates the effects of AL on PsyCap such that this relationship gets more pronounced in individuals with high levels of POS. All organizations in the education sector can benefit from the current study's practical application. We recommend that firms create and implement these training programs to improve JP since AL is favorably correlated with JP. The organization should pick executives with a vision to encourage e-JP. To promote this behavior, firms can also hold management training seminars, conferences, and programs. Making performance a clear necessity within job criteria will encourage it among personnel. To achieve great results, top management and leadership must inform the workforce about the importance of authentic behavior in the workplace.

20.
Elife ; 102021 08 20.
Article in English | MEDLINE | ID: mdl-34414885

ABSTRACT

Clustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly 1 µm, and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. Applying this approach to characterize the ephrinA1:EphA2 signaling system reveals that EphA2 clustering enhances both receptor phosphorylation and downstream signaling activity. Single-molecule imaging clearly resolves increased molecular binding dwell times at EphA2 clusters for both Grb2:SOS and NCK:N-WASP signaling modules. This type of intracellular comparison enables a substantially higher degree of quantitative analysis than is possible when comparisons must be made between different cells and essentially eliminates the effects of cellular response to ligand manipulation.


Subject(s)
Cell Membrane/metabolism , Receptor, EphA2/genetics , Signal Transduction/genetics , Humans , Ligands , Protein Binding , Protein Transport , Receptor, EphA2/metabolism
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