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1.
Nat Commun ; 15(1): 3799, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714769

ABSTRACT

Intriguing "slidetronics" has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

2.
J Hypertens ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38690935

ABSTRACT

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS AND RESULTS: VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR. CONCLUSIONS: Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.

3.
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
4.
J Cell Physiol ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558303

ABSTRACT

Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain-containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 µg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.

5.
Chem Biodivers ; 21(5): e202400031, 2024 May.
Article in English | MEDLINE | ID: mdl-38448389

ABSTRACT

Ulcerative colitis has been widely concerned for its persistent upward trend, and the sustained overproduction of pro-inflammatory cytokines such as IL-6 remains a crucial factor in the development of UC. Therefore, the identification of new effective drugs to block inflammatory responses is an urgent and viable therapeutic strategy for UC. In our research, twenty-three 6-acylamino/sulfonamido benzoxazolone derivatives were synthesized, characterized, and evaluated for anti-inflammatory activity against NO and IL-6 production in LPS-induced RAW264.7 cells. The results demonstrated that most of the target compounds were capable of reducing the overexpression of NO and IL-6 to a certain degree. For the most active compounds 3i, 3j and 3 l, the inhibitory activities were superior or equivalent to those of the positive drug celecoxib with a dose-dependent relationship. Furthermore, animal experiments revealed that active derivatives 3i, 3j and 3 l exhibited definitive therapeutical effect on DSS induced ulcerative colitis in mice by mitigating weight loss and DAI score while decreasing levels of pro-inflammatory cytokines such as IL-6 and IFN-γ, simultaneously increasing production of anti-inflammatory cytokines IL-10. In addition, compounds 3i, 3j and 3 l could also inhibit the oxidative stress to alleviate ulcerative colitis by decreasing MDA and MPO levels. These finding demonstrated that compounds 3i, 3j and 3 l hold significant potential as novel therapeutic agents for ulcerative colitis.


Subject(s)
Benzoxazoles , Colitis, Ulcerative , Interleukin-6 , Animals , Colitis, Ulcerative/drug therapy , Mice , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , Benzoxazoles/chemistry , Benzoxazoles/pharmacology , Benzoxazoles/chemical synthesis , RAW 264.7 Cells , Structure-Activity Relationship , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Nitric Oxide/biosynthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/therapeutic use , Dextran Sulfate , Drug Discovery , Molecular Structure , Dose-Response Relationship, Drug
6.
Heliyon ; 10(5): e27099, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463897

ABSTRACT

The ongoing pace of urbanization poses a substantial obstacle to the concurrent progress of both financial and ecological development. Recognizing this challenge, governments globally are formulating cutting-edge strategies for urban renewal to ensure the long-term sustainability of cities. In this context, we employ a difference-in-differences model to scrutinize the intricate relationship between smart cities and the growth of renewable energy, utilizing the Chinese smart city pilot program as a pertinent experiment. This analytical approach provides novel insights into the underlying reasons behind this correlation. The research yields three noteworthy findings. Firstly, it underscores the indispensable role of pilot initiatives in smart cities for advancing the cause of renewable energy. Secondly, the study reveals a positive and beneficial interplay between creativity, economic inclusion, and the utilization of technological innovation in experimental urban programs, suggesting a potential multiplier effect. Thirdly, the local context significantly influences the impact of smart city pilots, with the dissemination of renewable energy being particularly effective in resource-rich, metropolitan, and coastal cities. Observable impacts of current smart city experiment on energy security and sustainable development are already apparent. The research findings contribute fresh perspectives to the complex challenges of sustainable energy production and urban planning, especially in developing countries like China.

7.
Phys Chem Chem Phys ; 26(4): 3335-3341, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38197880

ABSTRACT

Ferroic compounds Fe2O(SeO3)2 (FSO) and Fe2(SeO3)3·3H2O (FSOH) prepared by the hydrothermal method are characterized and their optical properties are investigated by combining with first-principles calculations. The results show that (i) FSO is antiferromagnetic below ∼110 K and becomes ferromagnetic at elevated temperatures, while FSOH is antiferromagnetic at low temperatures probably due to a change in the spin state from Fe3+ (S = 5/2) to Fe2+ (S = 2); (ii) the optical bandgap is determined to be ∼2.83 eV for FSO and ∼2.15 eV for FSOH, consistent with the theoretical calculation; and (iii) the angle-resolved polarized Raman spectroscopy results of both crystals demonstrate the strong anisotropic light absorption and birefringence effects, and the unconventional symmetricity of some Raman modes is observed, which can be interpreted from the variation of Raman scattering elements. This work can provide not only an understanding of the structure and physical properties of iron selenites, but also a strategy for exploring the anomalous Raman behaviors in anisotropic crystals, facilitating the design and engineering of novel functional devices with low-symmetry ferroic materials.

8.
Molecules ; 29(2)2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38257279

ABSTRACT

Antibody arrays play a pivotal role in the detection and quantification of biomolecules, with their effectiveness largely dependent on efficient protein immobilization. Traditional methods often use heterobifunctional cross-linking reagents for attaching functional residues in proteins to corresponding chemical groups on the substrate surface. However, this method does not control the antibody's anchoring point and orientation, potentially leading to reduced binding efficiency and overall performance. Another method using anti-antibodies as intermediate molecules to control the orientation can be used but it demonstrates lower efficiency. Here, we demonstrate a site-specific protein immobilization strategy utilizing OaAEP1 (asparaginyl endopeptidase) for building a nanobody array. Moreover, we used a nanobody-targeting enhanced green fluorescent protein (eGFP) as the model system to validate the protein immobilization method for building a nanobody array. Finally, by rapidly enriching eGFP, this method further highlights its potential for rapid diagnostic applications. This approach, characterized by its simplicity, high efficiency, and specificity, offers an advancement in the development of surface-modified protein arrays. It promises to enhance the sensitivity and accuracy of biomolecule detection, paving the way for broader applications in various research and diagnostic fields.


Subject(s)
Antibodies , Cross-Linking Reagents
9.
ACS Nano ; 18(1): 164-177, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38133949

ABSTRACT

The rechargeable aqueous Zn ion battery (AZIB) is considered a promising candidate for future energy storage applications due to its intrinsic safety features and low cost. However, Zn dendrites and side reactions (e.g., corrosion, hydrogen evolution reaction, and inactive side product (Zn hydroxide sulfate) formation) at the Zn metal anode have been serious obstacles to realizing a satisfactory AZIB performance. The application of gel electrolytes is a common strategy for suppressing these problems, but the normally used highly cross-linked polymer matrix (e.g., polyacrylamide (PAM)) brings additional difficulties for battery assembly and recycling. Herein, we have developed a gel electrolyte for Zn metal anode stabilization, where a peptide matrix, a highly biocompatible material, is used for gel construction. Various experiments and simulations elucidate the sulfate anion-assisted self-assembly gel formation and its effect in stabilizing Zn metal anodes. Unlike polymer gel electrolytes, the peptide gel electrolyte can reversibly transform between gel and liquid states, thus facilitating the gel-involved battery assembly and recycling. Furthermore, the peptide gel electrolyte provides fast Zn ion diffusion (comparable to conventional liquid electrolyte) while suppressing side reactions and dendrite growth, thus achieving highly stable Zn metal anodes as validated in various cell configurations. We believe that our concept of gel electrolyte design will inspire more future directions for Zn metal anode protection based on gel electrolyte design.

10.
Langmuir ; 39(49): 17903-17920, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38039288

ABSTRACT

Coral reef survival is threatened globally. One way to restore this delicate ecosystem is to enhance coral growth by the controlled propagation of coral fragments. To be sustainable, this technique requires the use of biocompatible underwater adhesives. Hydrogels based on rationally designed ultrashort self-assembling peptides (USP) are of great interest for various biological and environmental applications, due to their biocompatibility and tunable mechanical properties. Implementing superior adhesion properties to the USP hydrogel compounds is crucial in both water and high ionic strength solutions and is relevant in medical and marine environmental applications such as coral regeneration. Some marine animals secrete large quantities of the aminoacids dopa and lysine to enhance their adhesion to wet surfaces. Therefore, the addition of catechol moieties to the USP sequence containing lysine (IIZK) should improve the adhesive properties of USP hydrogels. However, it is challenging to place the catechol moiety (Do) within the USP sequence at an optimal position without compromising the hydrogel self-assembly process and mechanical properties. Here, we demonstrate that, among three USP hydrogels, DoIIZK is the least adhesive and that the adhesiveness of the IIZDoK hydrogel is compromised by its poor mechanical properties. The best adhesion outcome was achieved using the IIZKDo hydrogel, the only one to show equally sound adhesive and mechanical properties. A mechanistic understanding of this outcome is presented here. This property was confirmed by the successful gluing of coral fragments by means of IIZKDo hydrogel that are still thriving after more than three years since the deployment. The validated biocompatibility of this underwater hydrogel glue suggests that it could be advantageously implemented for other applications, such as surgical interventions.


Subject(s)
Anthozoa , Environmental Restoration and Remediation , Hydrogels , Animals , Adhesives/chemistry , Dihydroxyphenylalanine/chemistry , Ecosystem , Hydrogels/chemistry , Lysine , Peptides
11.
J Agric Food Chem ; 71(44): 16807-16814, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37879039

ABSTRACT

The contamination of food by pathogens is a serious problem in global food safety, and current methods of detection are costly, time-consuming, and cumbersome. Therefore, it is necessary to develop rapid, portable, and sensitive assays for foodborne pathogens. In addition, assays for foodborne pathogens must be resistant to interference resulting from the complex food matrix to prevent false positives and negatives. In this study, hemin and reduced graphene oxide-MoS2 sheets (GMS) were used to design a near-infrared (NIR)-responsive photoelectrochemical (PEC) aptasensor with target-induced photocurrent polarity switching based on a hairpin aptamer (Hp) with a G-quadruplex motif. A ready-to-use analytical device was developed by immobilizing GMS on the surface of a commercial screen-printed electrode, followed by the attachment of the aptamer. In the presence of Escherichia coli O157:H7, the binding sites of Hp with the G-quadruplex motif were opened and exposed to hemin, leading to the formation of a G-quadruplex/hemin DNAzyme. Crucially, after binding to hemin, the charge transfer pathway of GMS changes, resulting in a switch of the photocurrent polarity. Further, G-quadruplex/hemin DNAzyme enhanced the cathodic photocurrent, and the proposed sensor exhibited a wide linear range ((25.0-1.0) × 107 CFU/mL), a low limit of detection (2.0 CFU/mL), and good anti-interference performance. These findings expand the applications of NIR-responsive PEC materials and provide versatile PEC methods for detecting biological analytes, especially for food safety testing.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , DNA, Catalytic , Escherichia coli O157 , Escherichia coli O157/genetics , Escherichia coli O157/metabolism , DNA, Catalytic/chemistry , Hemin/chemistry , Biosensing Techniques/methods , Aptamers, Nucleotide/genetics , Aptamers, Nucleotide/chemistry
12.
Nat Commun ; 14(1): 6315, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37813847

ABSTRACT

Mechanical sensors are mainly divided into two types (vertical force sensing and lateral strain sensing). Up to now, one sensor with two working modes is still a challenge. Here, we demonstrate a structural design concept combing a piezoelectric nano/microwire with a flexible polymer with protrusions that enables a dual-modal piezotronic transistor (DPT) with two working modes for highly sensitive vertical force sensing and lateral strain sensing. For vertical force sensing, DPT exhibits a force sensitivity up to 221.5 N-1 and a minimum identifiable force down to 21 mN, corresponding to a pressure sensitivity of 1.759 eV/MPa. For lateral strain sensing, DPT can respond to a large compression strain (~5.8%) with an on/off ratio up to 386.57 and a gauge factor up to 8988.6. It is a universal design that can integrate vertical force sensing and lateral strain sensing into only one nanodevice, providing a feasible strategy for multimodal devices.

13.
Nat Immunol ; 24(11): 1813-1824, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37813965

ABSTRACT

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.


Subject(s)
Cytophagocytosis , Kupffer Cells , Humans , Phagocytosis/genetics , Galectins/genetics , Galectins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism
14.
Chem Sci ; 14(35): 9496-9502, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37712017

ABSTRACT

An axially chiral styrene-based organocatalyst, featuring a combination of axially chiral styrene-based structure and a pyrrole ring, has been designed and synthesized. This catalyst demonstrates remarkable capabilities in producing a wide range of densely substituted spirooxindoles that feature an alkyne-substituted quaternary stereogenic center. These spirooxindoles are generated through mild cascade Michael/cyclization reactions, resulting in high conversion rates and exceptional enantioselectivity. Our catalytic model, based on experiments, X-ray structure analysis and DFT calculations suggests that chiral matched π-π interactions and multiple H-bonds between the organocatalyst and substrates play significant roles in controlling the stereoselectivity of the reaction.

15.
Nanoscale ; 15(38): 15450-15471, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37721398

ABSTRACT

Against the backdrop of advocacy for green and low-carbon development, electrochromism has attracted academic and industrial attention as an intelligent and energy-saving applied technology due to its optical switching behavior and its special principles of operation. Inorganic electrochromic materials, represented by transition metal oxides, are considered candidates for the next generation of large-scale electrochromic applied technologies due to their excellent stability. However, the limited color diversity and low color purity of these materials greatly restrict their development. Starting from the multicolor properties of inorganic electrochromic materials, this review systematically elaborates on recent progress in the aspects of the intrinsic multicolor of electrochromic materials, and structural multicolor based on the interaction between light and microstructure. Finally, the challenges and opportunities of inorganic electrochromic technology in the field of multicolor are discussed.

16.
Cell Mol Biol (Noisy-le-grand) ; 69(8): 246-249, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37715373

ABSTRACT

To elucidate the role of microRNA-1284 (miR-1284) in the onset of thyroid cancer (TC) and its underlying mechanism. Differential expressions of miR-1284 in TC and thyroid tissues were detected. Regulatory effects of miR-1284 on proliferative, migratory, apoptotic potentials and cell cycle progression were assessed. In addition, miR-1284 levels in TC tissues and peripheral blood of TC patients were determined as well. Through collecting culture medium and exosomes of PTC cells, changes in miR-1284 levels were examined. MiR-1284 was downregulated in TC than normal thyroid tissues. Overexpression of miR-1284 attenuated proliferative and migratory potentials, but induced apoptosis in TPC-1 and FTC-133 cells. Moreover, overexpression of miR-1284 upregulated E-cadherin and downregulated N-cadherin in papillary TC (PTC) cells. MiR-1284 was downregulated in TC tissues, while its level in the peripheral blood of TC patients was upregulated. Besides, miR-1284 was upregulated in the culture medium and exosomes of PTC cells, which was reversed by Brefeldin A treatment. Overexpression of miR-1284 suppresses proliferative and migratory potentials and induces apoptosis in TC. Upregulated miR-1284 in the peripheral blood of TC patients may be derived from exosomes secreted by PTC cells.


Subject(s)
MicroRNAs , Thyroid Neoplasms , Humans , Thyroid Neoplasms/genetics , Thyroid Cancer, Papillary , Cell Division , Culture Media , MicroRNAs/genetics
18.
Life Sci ; 330: 122023, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37579834

ABSTRACT

Enhanced proliferation and migration of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling in hypertension. Adventitial fibroblasts (AFs)-derived extracellular vesicles (EVs) modulate vascular remodeling in spontaneously hypertensive rat (SHR). This study shows the important roles of EVs-mediated miR-21-3p transfer in VSMC proliferation and migration and underlying mechanisms in SHR. AFs and VSMCs were obtained from aorta of Wistar-Kyoto rat (WKY) and SHR. EVs were separated from AFs culture with ultracentrifugation method. MiR-21-3p content in the EVs of SHR was increased compared with those of WKY. MiR-21-3p mimic promoted VSMC proliferation and migration of WKY and SHR, while miR-21-3p inhibitor attenuated proliferation and migration only in the VSMCs of SHR. EVs of SHR stimulated VSMC proliferation and migration, which were attenuated by miR-21-3p inhibitor. Sorbin and SH3 domain containing 2 (SORBS2) mRNA and protein levels were reduced in the VSMCs of SHR. MiR-21-3p mimic inhibited, while miR-21-3p inhibitor promoted SORBS2 expressions in the VSMCs of both WKY and SHR. EVs of SHR reduced SORBS2 expression, which was prevented by miR-21-3p inhibitor. EVs of WKY had no significant effect on SORBS2 expressions. SORBS2 overexpression attenuated the roles of miR-21-3p mimic and EVs of SHR in promoting VSMC proliferation and migration of SHR. Overexpression of miR-21-3p in vivo promotes vascular remodeling and hypertension. These results indicate that miR-21-3p in the EVs of SHR promotes VSMC proliferation and migration via negatively regulating SORBS2 expression.


Subject(s)
Extracellular Vesicles , Hypertension , MicroRNAs , Rats , Animals , Rats, Inbred SHR , Muscle, Smooth, Vascular/metabolism , Rats, Inbred WKY , Vascular Remodeling , Extracellular Vesicles/metabolism , MicroRNAs/metabolism , Cell Proliferation , Fibroblasts/metabolism , Cells, Cultured , Myocytes, Smooth Muscle/metabolism
19.
Front Public Health ; 11: 1233637, 2023.
Article in English | MEDLINE | ID: mdl-37637823

ABSTRACT

Background: Tuberculosis (TB) remains a major public health challenge. However, indicators of delays in assessing effective TB prevention and control and its influencing factors have not been investigated in the eastern coastal county of China. Methods: All notified pulmonary tuberculosis (PTB) cases in the Fenghua District, China were collected between 2010 and 2021 from the available TB information management system. Comparison of delays involving patient, health system, and total delays among local and migrant cases. Additionally, in correlation with available Basic Public Health Service Project system, we performed univariate and multivariate logistic regression analyses identified the influencing factors associated with patient and total delays in patients aged >60 years. Results: In total, 3,442 PTB cases were notified, including 1,725 local and 1,717 migrant patients, with a male-to-female ratio of 2.13:1. Median patient and total delays of local TB patients were longer than those for migrant patients; the median health system delay did not show any significant difference. For patient delay among the older adult, female (cOR: 1.93, 95% CI: 1.07-3.48), educational level of elementary school and middle school (cOR: 0.23, 95% CI: 0.06-0.84) had a statistical difference from univariable analysis; however, patients without diabetes showed a higher delay for multiple-factor analysis (aOR: 2.12, 95% CI: 1.02-4.41). Furthermore, only the education level of elementary school and middle school presented a low total delay for both univariate (cOR: 0.22, 95% CI: 0.06-0.82) and multivariate analysis (aOR: 0.21, 95% CI: 0.05-0.83) in the older patients. Conclusion: The delay of TB cases among migrants was lower than the local population in the Fenghua District, which may be related to the "healthy migrant effect". It highlights that women, illiterate people, and people without diabetes are key groups for reducing delays among older adults. Health awareness should focus on these target populations, providing accessible health services, and reducing the time from symptom onset to diagnosis.


Subject(s)
Tuberculosis, Pulmonary , Humans , Female , Male , Aged , Tuberculosis, Pulmonary/epidemiology , China/epidemiology , Educational Status , Schools , Factor Analysis, Statistical
20.
JACS Au ; 3(7): 1902-1910, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37502147

ABSTRACT

A cluster of several newly occurring mutations on Omicron is found at the ß-core region of the spike protein's receptor-binding domain (RBD), where mutation rarely happened before. Notably, the binding of SARS-CoV-2 to human receptor ACE2 via RBD happens in a dynamic airway environment, where mechanical force caused by coughing or sneezing occurs. Thus, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to measure the stability of RBDs and found that the mechanical stability of Omicron RBD increased by ∼20% compared with the wild type. Molecular dynamics (MD) simulations revealed that Omicron RBD showed more hydrogen bonds in the ß-core region due to the closing of the α-helical motif caused primarily by the S373P mutation. In addition to a higher unfolding force, we showed a higher dissociation force between Omicron RBD and ACE2. This work reveals the mechanically stabilizing effect of the conserved mutation S373P for Omicron and the possible evolution trend of the ß-core region of RBD.

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