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1.
bioRxiv ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39026836

ABSTRACT

Prime editing has emerged as a precise and powerful genome editing tool, offering a favorable gene editing profile compared to other Cas9-based approaches. Here we report new nCas9-DNA polymerase fusion proteins to create chimeric oligonucleotide-directed editing (CODE) systems for search-and-replace genome editing. Through successive rounds of engineering, we developed CODEMax and CODEMax(exo+) editors that achieve efficient genome modifications in human cells with low unintended edits. CODEMax and CODEMax(exo+) contain an engineered Bst DNA polymerase derivative known for its robust strand displacement ability. Additionally, CODEMax(exo+) features a 5' to 3' exonuclease activity that promotes effective strand invasion and repair outcomes favoring the incorporation of the desired edit. We demonstrate CODEs can perform small insertions, deletions, and substitutions with improved efficiency compared to PEMax at many loci. Overall, CODEs complement existing prime editors to expand the toolbox for genome manipulations without double-stranded breaks.

2.
J Mol Diagn ; 26(7): 599-612, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38901927

ABSTRACT

The high disease burden of influenza virus poses a significant threat to human health. Optimized diagnostic technologies that combine speed, sensitivity, and specificity with minimal equipment requirements are urgently needed to detect the many circulating species, subtypes, and variants of influenza at the point of need. Here, we introduce such a method using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform. Four SHINE assays were designed and validated for the detection and differentiation of clinically relevant influenza species (A and B) and subtypes (H1N1 and H3N2). When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously. This study demonstrates the utility of this duplex assay in discriminating two alleles of an oseltamivir resistance (H275Y) mutation as well as in simultaneously detecting influenza A and human RNAse P in patient samples. These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance.


Subject(s)
CRISPR-Cas Systems , Influenza, Human , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , CRISPR-Cas Systems/genetics , Sensitivity and Specificity , RNA, Viral/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Molecular Diagnostic Techniques/methods , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A virus/genetics , Influenza A virus/isolation & purification , Influenza A virus/classification
3.
Adv Physiol Educ ; 48(3): 498-504, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38695082

ABSTRACT

Embedding clinically relevant learning experience in basic science subjects is desired for the preclinical phase of undergraduate medical education. The present study aimed to modify case-based learning (CBL) with a role-playing situational teaching method and assess the student feedback and learning effect. One hundred seventy-six sophomore students majoring in clinical medicine from Harbin Medical University were randomly divided into two groups: the control group (n = 90), who received traditional hybrid teaching, and the experimental group (n = 86), who received the role-playing situational teaching. Students in the experimental group were given a 1-wk preclass preparation to dramatize a hyperthyroidism scenario through online autonomous learning of thyroid physiology and performed the patient's consultation process in class, followed by a student presentation about key points of lecture content and a question-driven discussion. A posttest and questionnaire survey were conducted after class. The test scores of the two groups had no statistical differences, whereas the rate of excellence (high scores) of the experimental group was significantly higher than that of the control group. Furthermore, the record of online self-directed learning engagements was significantly improved in the experimental group. In the questionnaire, >70% of the students showed positive attitudes toward the role-playing situational teaching method and were willing to participate in other chapters of the physiology course. Such results show that CBL supported by a role-playing situational teaching method encourages active learning and improves the application of basic knowledge of physiology, which can be incorporated in the preclinical curricula to bridge the gap between theory and practice.NEW & NOTEWORTHY Formal application through structured role-play is often overlooked in physiology education. In traditional case-based learning (CBL), clinical cases are the subject and unfocused discussion often occurs. The present study aimed to modify CBL with a role-playing situational teaching method and assess the student feedback and learning effect. The results show that the new teaching model encourages active learning and improves the application of basic knowledge of physiology.


Subject(s)
Education, Medical, Undergraduate , Physiology , Problem-Based Learning , Students, Medical , Humans , Physiology/education , Problem-Based Learning/methods , Education, Medical, Undergraduate/methods , Female , Endocrinology/education , Male , Role Playing , Teaching , Educational Measurement/methods , Young Adult
4.
J Affect Disord ; 359: 196-205, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38777265

ABSTRACT

BACKGROUND: This study examines the extent to which depressive symptoms mediate the link between childhood friendship (CF) and physical function among middle-aged and older adults in China. METHODS: China Health and Retirement Longitudinal Study (CHARLS) data were used; specifically, CHARLS life history survey (conducted from June 1-December 31, 2014) and follow-up health survey (conducted from July 1-September 30, 2015) data were used. The Sobel test, Bootstrap test and multivariable logistic regression were performed to examine the mediating role of depressive symptoms (measured by the 10-item Center for Epidemiologic Studies Depression Scale) in the association between CF (measured by a standardized retrospective questionnaire) and physical function, which was measured by basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and grip strength. RESULTS: A total of 12,170 participants aged 45 years or older were included in this cross-sectional study. After controlling for covariates, low-quality CF was associated with an increased prevalence of BADL disability (OR = 1.18; 95 % CI = 1.05-1.32), IADL disability (OR = 1.25; 95 % CI = 1.12-1.40), and low grip strength (OR = 1.21; 95 % CI = 1.09-1.34). The proportion of the mediating effect of depressive symptoms was 48 % for CF and BADL, 40 % for CF and IADL, and 11 % for CF and grip strength. Depressive symptoms and worse CF have a joint effect on BADL disability (OR = 3.30; 95 % CI = 2.82-3.85), IADL disability (OR = 3.52; 95 % CI = 3.03-4.09), and low grip strength (OR = 1.65; 95 % CI = 1.43-1.92). LIMITATIONS: Not all potential confounding factors (such as childhood behavioural problems, genetic factors, and memory function) were measured in the analysis, and there may have been recall bias in the retrospective collection of CF data. CONCLUSIONS: Individuals with high-quality CF were more likely to have a decreased prevalence of impaired physical function in later life. Depressive symptoms acted as a mediator associated with the development of CF.


Subject(s)
Activities of Daily Living , Depression , Friends , Humans , Male , Female , China/epidemiology , Longitudinal Studies , Depression/epidemiology , Aged , Middle Aged , Cross-Sectional Studies , Friends/psychology , Retirement/statistics & numerical data , Retirement/psychology , Hand Strength , Prevalence
5.
Int J Biol Macromol ; 264(Pt 2): 130821, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484816

ABSTRACT

Cellulose nanofibers (CNF) based films are promising packaging materials, but the lack of special functions (especially UV-shielding property) usually restrict their further applications. In this work, MXene was incorporated into the CNF film by a direct solvent volatilization induced film forming method to study its UV-shielding property for the first time, which avoided the using of a vacuum filtration equipment. The composite films containing glycerin could be folded repeatedly without breaking, showing good flexibility. The structure and properties of MXene/CNF composite films (CMF) were characterized systematically. The results showed that MXene distributed uniformly in the CNF film matrix and there was strong hydrogen bonding interaction between CNF and MXene. The tensile strength and Young's modulus of the composite films could reach 117.5 MPa and 2.23 GPa, which was 54.1 % and 59.2 % higher than those of pure CNF film, respectively. With the increase of MXene content, both the UVA and UVB shielding percentages increased significantly from 17.2 % and 25.5 % to 100.0 %, showing excellent UV-shielding property. Moreover, CMF exhibited a low oxygen permeability (OP) value of 0.39 cc µm d-1 m-2 kPa-1, a low water vapor permeability (WVP) value of 5.13 × 10-11 g-1s-1Pa-1 and a high antibacterial rate against E. coli (94.1 % at 24 h), showing potential application in the packaging field.


Subject(s)
Cellulose , Nanofibers , Nitrites , Transition Elements , Cellulose/chemistry , Nanofibers/chemistry , Escherichia coli , Product Packaging
6.
Environ Int ; 184: 108475, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38340408

ABSTRACT

Climate change triggered more environmental extremes. The joint events of air pollution wave and cold wave showed higher health risks than independent events, but little evidence is available for the spatiotemporal features of their co-occurrence. To better understand and forecast the joint events, a method framework was developed in this study. The temporal trend and spatial distribution of count and duration for joint events were measured at each grid cell (0.5°×0.5°) by integrating the PM2.5 air pollution wave and cold wave. The generalized linear mixed model was used to screen influencing variables that took into account socioeconomic characteristics, meteorological variables, and annual PM2.5 levels. During 2000 and 2018, the average annual count of joint events was 4.1 ± 6.8 days and the average duration ranged from 1.0 to 9.7 days. High spatial heterogeneity was observed throughout China, with a significant increase in joint events observed in Xinjiang area (the largest province in China). The most average count of joint events was observed in Henan province (one of the most populous provinces), while the longest duration was in Chongqing (a municipality, one of the megacities). Areas with higher PM2.5 levels, prolonged air pollution wave, and cold wave durations would experience more joint events. These findings can assist China in locating vulnerable areas and establishing effective local early warning systems. The method framework offers broader perspectives on mitigating health risks associated with extreme events in other countries and regions.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Particulate Matter/analysis , Environmental Monitoring/methods , Air Pollution/analysis , China , Cities
7.
Oncogenesis ; 13(1): 3, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38191478

ABSTRACT

Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.

8.
Cell Death Dis ; 15(1): 69, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238314

ABSTRACT

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.


Subject(s)
DNA Polymerase II , Endometrial Neoplasms , Female , Humans , Carcinogenesis/genetics , Cell Transformation, Neoplastic , DNA , DNA Polymerase II/genetics , DNA Polymerase II/metabolism , Endometrial Neoplasms/genetics , Mutation/genetics , Poly-ADP-Ribose Binding Proteins/genetics
9.
Eur J Pharmacol ; 966: 176339, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38272342

ABSTRACT

Autophagy is closely related to the aging of various organ systems, including ovaries. Quercetin has a variety of biological activities, including potential regulation of autophagy. However, whether quercetin-regulated autophagy activity affects the process of ovarian aging and injury has not been clarified yet. This study explores whether quercetin can resist H2O2-induced aging and injury of granulosa cells by regulating autophagy and its related molecular mechanisms in vitro experiments. The cell viability, endocrine function, cell aging, and apoptosis were detected to evaluate the effects of quercetin and autophagy regulators like 3-methyladenine and rapamycin. The levels of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 were determined by Western blot to assess the effects of quercetin, 3-methyladenine and rapamycin on autophagy. Our results showed quercetin resisted H2O2-induced granulosa cell aging and injury by activating protective autophagy. The treatment of 3-methyladenine and rapamycin confirmed the protective function of autophagy in H2O2-induced granulosa cells. 3-methyladenine treatment inhibited the expression of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 and abolished the positive effects on cell viability, estradiol secretion, and cell apoptosis activated by quercetin. In conclusion, quercetin activates autophagy by upregulating the expression of autophagy-related proteins to resist H2O2-induced aging and injury, which is crucial for stabilizing the function of granulosa cells under oxidative injury conditions and delaying aging. This study may explain the protective effects of quercetin on ovarian aging and injury from the perspective of regulating autophagy.


Subject(s)
Hydrogen Peroxide , Quercetin , Female , Rats , Animals , Quercetin/pharmacology , Hydrogen Peroxide/toxicity , Hydrogen Peroxide/metabolism , Beclin-1/metabolism , Granulosa Cells , Aging , Apoptosis , Autophagy , Sirolimus/pharmacology
10.
Neurol Sci ; 45(4): 1565-1580, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37947983

ABSTRACT

BACKGROUND: Brain tumor patients undergoing craniotomy are significantly associated with the development of venous thromboembolism (VTE), while the contributing factors remains controversial. Our study aimed to investigate the prevalence and risk factors for VTE in postoperational brain tumor patients. METHODS: We searched the PubMed, Embase, Web of Science, Medline, and Cochrane Library databases from their inception to July 2023. Article selection, data extraction, and study quality assessment were performed independently by two reviewers. Publication bias was assessed using Egger's and Begg's tests. Stata 15.0 software was used for data analysis. RESULTS: A total of 25 studies were considered, with a total of 49,620 brain tumor individuals. The pooled prevalence of VTE during hospitalization in postoperational brain tumor patients was 9% [95% CI: (0.08, 0.10)]. Moreover, our results demonstrated that patients with VTE were older than those without VTE [mean difference [MD] = 8.14, 95% CI: (4.97, 11.30)]. The following variables were significantly associated with VTE: prior history of VTE [OR = 7.81, 95% CI: (3.62, 16.88)], congestive heart failure [OR = 2.33, 95% CI: (1.08-5.05)], diabetes [OR = 1.87, 95% CI: (1.12-3.10)], hypertension [OR = 1.27, 95% CI: (1.07-1.50)], steroid use [OR = 1.63, 95% CI: (1.41, 1.88)], high white blood cells counts [MD = 0.32, 95% CI: (0.01, 0.63)], and high fibrinogen levels [MD = 0.19, 95% CI: (0.08, 0.30)]. CONCLUSION: This meta-analysis identified risk factors for postoperational VTE in patients with brain tumor, which can serve as a theoretical foundation for medical staff to manage and treat VTE. TRIAL REGISTRATION: CRD42023357459.


Subject(s)
Brain Neoplasms , Venous Thromboembolism , Humans , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/surgery , Prevalence , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Brain Neoplasms/complications , Brain Neoplasms/surgery , Craniotomy/adverse effects , Risk Factors
11.
Magn Reson Med ; 91(6): 2310-2319, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38156825

ABSTRACT

PURPOSE: This study aimed to evaluate the potential of 3D EPI for improving the reliability of T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted data and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ decay rate and susceptibility (χ) compared with conventional gradient-echo (GRE)-based acquisition. METHODS: Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ were quantified, and their interscan differences were used to evaluate the test-retest reliability. Interprotocol differences of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ between GRE and EPI were also measured voxel by voxel and in selected regions of interest to test the consistency between the two acquisition methods. RESULTS: The quantifications of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. CONCLUSION: The result suggests that multishot multi-echo 3D EPI can be a useful alternative acquisition method for T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ with reduced scan time, improved test-retest reliability, and similar accuracy compared with commonly used 3D GRE.


Subject(s)
Echo-Planar Imaging , Magnetic Resonance Imaging , Humans , Echo-Planar Imaging/methods , Reproducibility of Results , Healthy Volunteers
12.
Front Med (Lausanne) ; 10: 1283302, 2023.
Article in English | MEDLINE | ID: mdl-38076266

ABSTRACT

Introduction: Aging leads to significant structural and functional changes in blood vessels, which disrupt their normal function and impact cardiovascular health. Current research is actively exploring the NRF2 antioxidative pathway, recognizing its role in protecting cells by preserving their antioxidant defenses against damage. However, there has been limited exploration into the role of the NRF2 pathway in vascular aging. The primary objective of this study was to determine whether age-related changes in the aorta are associated with variations in the baseline levels of antioxidant enzymes, with a particular emphasis on how the NRF2 pathway operates in the aortic wall. Methods: A group of healthy aging female SD rats was compared with their younger counterparts. Various assessments were conducted, including measuring blood pressure, analyzing serum lipid profiles, examining aortic tissue, and assessing the expression of antioxidant enzymes. Results: The results revealed significant differences in both blood pressure and serum lipid levels between the aged and younger rats. The examination of the aorta in older rats showed structural alterations, increased apoptosis, and the accumulation of fatty deposits. In the older rats, levels of SOD-1 (superoxide dismutase) and GSS (glutathione synthetase) were lower, whereas NRF2, KEAP-1 (Kelch-like ECH-associated protein 1), and HO-1 (Heme oxygenase 1) were higher. Discussion: This study advances our understanding of how aging affects the antioxidant system in blood vessels, particularly in relation to the regulation of the NRF2/HO-1 pathway in the aorta. These findings suggest that targeting the NRF2/HO-1 pathway could present anovel therapeutic approach for addressing age-related vascular issues.

13.
Free Radic Biol Med ; 208: 759-770, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37774802

ABSTRACT

BACKGROUND: Preeclampsia is a placentally induced syndrome with diverse clinical presentation that currently has no cure. Oxidative stress is a potent inducer of placental dysfunction. The apelin receptor (APJ) system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. This study examines the alteration of circulating apelin levels and placental APJ expression in preeclampsia and investigates whether apelin/APJ system can protect placental trophoblast from hypoxia-induced oxidative stress injury through PI3K/AKT signaling pathway. RESULTS: Our results confirmed that maternal apelin concentration was increased in women with preeclampsia, but APJ expression was reduced in the preeclamptic placentas. Apelin-13 treatment not only specifically attenuated CoCl2-induced superoxide production, but also prevented CoCl2-induced reduction of SOD activity and SOD1 expression. In addition, apelin-13 suppressed CoCl2-induced apoptosis by increasing the expression of bcl-2/bax ratio and by decreasing the expression of active caspase-3 in placental trophoblasts. Furthermore, we found that apelin-13 binding APJ activated the PI3K and AKT kinases and inhibition of PI3K kinase significantly blocked the anti-oxidative effects of apelin-13 in placental trophoblasts. CONCLUSIONS: Decrease of placental APJ expression is associated with oxidative stress-induced placental dysfunction in preeclampsia, and increased circulating apelin could be a moderately successful marker to differentiate subjects with preeclampsia from healthy pregnant women. Inhibition of superoxide production and caspase-3 cleavage, together with upregulation of SOD activity/expression and bcl-2/bax ratio, could be the potential molecular mechanisms by which apelin-13/APJ protects placental trophoblasts from oxidative stress injury.


Subject(s)
Oxidative Stress , Pre-Eclampsia , Trophoblasts , Female , Humans , Pregnancy , Apelin/genetics , Apelin/metabolism , Apelin/pharmacology , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Hypoxia/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Pre-Eclampsia/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Superoxide Dismutase/metabolism , Superoxides/metabolism , Trophoblasts/metabolism
14.
ArXiv ; 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37645047

ABSTRACT

This study aimed to evaluate the potential of 3D echo-planar imaging (EPI) for improving the reliability of T2*-weighted (T2*w) data and quantification of R2* decay rate and susceptibility (χ) compared to conventional gradient echo (GRE)-based acquisition. Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R2* and χ were quantified and compared using their inter-scan difference to evaluate the test-retest reliability. Inter-protocol differences of R2* and χ between GRE and EPI were also measured voxel by voxel and in selected ROIs to test the consistency between the two acquisition methods. The quantifications of R2* and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. This result suggested multi-shot multi-echo 3D EPI can be a useful alternative acquisition method for T2*w MRI and quantification of R2* and χ with reduced scan time, improved test-retest reliability and similar accuracy compared to commonly used 3D GRE.

15.
Int J Mol Sci ; 24(13)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37446088

ABSTRACT

Resveratrol performs a variety of biological activities, including the potential regulation of autophagy. However, it is unclear whether resveratrol protects against luteal dysfunction and whether autophagy involves the regulation of resveratrol. This study aims to investigate whether resveratrol can regulate autophagy to resist H2O2-induced luteinized granulosa cell dysfunction in vitro. Our results showed that resveratrol can enhance cell viability, stimulate the secretion of progesterone and estradiol, and resist cell apoptosis in H2O2-induced luteinized granulosa cell dysfunction. Resveratrol can activate autophagy by stimulating the expression of autophagy-related genes at the transcriptional and translational levels and increasing the formation of autophagosomes and autophagolysosomes. Rapamycin, 3-methyladenine, and bafilomycin A1 regulated the levels of autophagy-related genes in H2O2-induced luteinized granulosa cell dysfunction and further confirmed the protective role of autophagy activated by resveratrol. In conclusion, resveratrol activates autophagy to resist H2O2-induced oxidative dysfunction, which is crucial for stabilizing the secretory function of luteinized granulosa cells and inhibiting apoptosis. This study may contribute to revealing the protective effects of resveratrol on resisting luteal dysfunction from the perspective of regulating autophagy.


Subject(s)
Granulosa Cells , Hydrogen Peroxide , Female , Rats , Animals , Resveratrol/pharmacology , Resveratrol/metabolism , Hydrogen Peroxide/metabolism , Granulosa Cells/metabolism , Progesterone/metabolism , Autophagy , Cells, Cultured
16.
Small ; 19(46): e2303008, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37485638

ABSTRACT

There is an urgent demand of ultrathin high-performance microwave absorbing materials (MAMs) in the electromagnetic protection field. However, minimizing thickness is challenging mainly due to dielectric mismatch at high permittivity from excessive dielectric loss, leading to strong reflection at 2-18 GHz. Here, a hybrid TaS2 /Co(Cp)2 superlattice is fabricated with alternating [TaS2 ] inorganic layers and [Co(Cp)2 ] organic layers. Dynamic Ta─Co dipoles offer a unique interfacial polarization relaxation mechanism involving the inversion and rotation of dynamic Ta─Co dipoles. The prolonged relaxation time of limited dynamic Ta─Co dipoles contributes to enhanced dielectric matching at high permittivity, which is essential for ultrathin high-performance MAMs. Furthermore, the confinement of paramagnetic Co(Cp)2 molecules in the interlayer space of the diamagnetic TaS2 sublattice triggers unexpected ferromagnetism via interfacial magnetic coupling conducive to the improved microwave-absorbing performance at reduced thickness. Therefore, it presents a 1.271-mm thick ultrathin absorber that can attenuate up to 99.99% of electromagnetic wave energy with a broad effective absorption bandwidth of 4.05 GHz, thus pushing the limits of thickness of 2D-based high-performance MAMs. This paper demonstrates a new strategy toward ultrathin MAMs with tunable and decent electromagnetic loss derived from electrical and magnetic coupling at the atomic scale.

17.
Sci Adv ; 9(24): eade6624, 2023 06 16.
Article in English | MEDLINE | ID: mdl-37315132

ABSTRACT

DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8+ T cells. Our study reveals an unidentified role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting that SMYD2 is a promising therapeutic target for cancer treatment.


Subject(s)
CD8-Positive T-Lymphocytes , DNA End-Joining Repair , Histone-Lysine N-Methyltransferase , Ku Autoantigen , Chromatin , Lysine , Ku Autoantigen/metabolism , Histone-Lysine N-Methyltransferase/metabolism
18.
Mil Psychol ; 35(1): 76-84, 2023.
Article in English | MEDLINE | ID: mdl-37130562

ABSTRACT

Military personnel live in operating environments in which poor sleep is common. In this cross-temporal meta-analysis (CTMA), 100 studies (144 data sets, N = 75,998) were identified to examine changes in sleep quality among Chinese active service personnel from 2003 to 2019. Participants were divided into three groups: the navy, the non-navy, and the unknown service. The Pittsburgh Sleep Quality Index (PSQI) was used as the measure of sleep quality; it contains a global score and seven component scores, with higher scores indicative of poorer sleep. Among all active military personnel, the PSQI global and seven component scores decreased from 2003 to 2019. In examining the results by military type, the PSQI global and seven component scores increased in the navy group. Conversely, both the non-navy and unknown-service groups showed decreased PSQI global scores over time. Similarly, all PSQI component scores decreased over time for both the non-navy and unknown service groups, except for the use of sleeping medication (USM), which increased in the non-navy group. In conclusion, the sleep quality of Chinese active service personnel showed a positive trend. Further research should focus on improving the navy's sleep quality.


Subject(s)
Military Personnel , Sleep Quality , Humans , Asian People , East Asian People , Sleep
19.
Sleep Breath ; 27(6): 2499-2507, 2023 12.
Article in English | MEDLINE | ID: mdl-37059903

ABSTRACT

PURPOSE: This study explored the relationship between naps and memory among habitual nappers in China. METHODS: Medical college students participated and were divided into 30-min, 60-min, and 90-min time-in-bed groups. To evaluate declarative and procedural memory performance, A-B and A-C interfering word pair and interfering finger tapping tasks were employed. RESULTS: Among 60 students, a significant decrease in the correct recall rate in the declarative task after having a nap was found only in the 30-min group (p = 0.005). After learning interference (A-C word pairs), the correct recall rate for the declarative task decreased significantly in all interference tests (ps < 0.001). In the procedural task, the speed of sequence A in the retests increased after having a nap in all three groups (ps < 0.048), with a significant decrease in accuracy only in the 30-min group (p = 0.042). After learning interference (sequence B) in the procedural task, the speed of sequence A increased in the 60-min group after 1 h (p = 0.049), and both the 60-min and 90-min groups showed increased speed after one night (ps < 0.022). No significant improvement in speed was found in the 30-min group (ps > 0.05), and this group showed the lowest accuracy for sequence A (ps < 0.16). CONCLUSION: A habitual nap time-in-bed of 60 or 90 min had better effects on declarative and procedural memory consolidation and better memory resistance against interference in procedural memory.


Subject(s)
Memory Consolidation , Humans , Mental Recall , China , Sleep
20.
Neuroimage ; 270: 119992, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36858332

ABSTRACT

MR images of the effective relaxation rate R2* and magnetic susceptibility χ derived from multi-echo T2*-weighted (T2*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R2* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R2* and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T2*w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B0 changes was deployed using volumetric navigators. Such correction improved the T2*w image quality rated by experienced image readers and test-retest reliability of R2* and χ quantification with reduced median inter-scan differences up to 10 s-1 and 5 ppb, respectively. R2* and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s-1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R2* or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R2* and χ along the cortical depth at submillimeter resolution and the need for motion and B0 corrections for their robust quantification in vivo.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Reproducibility of Results , Retrospective Studies , Magnetic Resonance Imaging/methods , Motion
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