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1.
Article in English | MEDLINE | ID: mdl-38598173

ABSTRACT

Motivated by the surging demand for low-temperature waste heat harvesting, materials with both prominent thermoelectric and good mechanical properties are preferred in practical applications. In this present work, the composite exploration of Te-doped Mg3.2Bi1.5Sb0.5-x vol % nanosized SiC (x = 0, 0.05, 0.1, 0.2, and 0.5) was carried out, where nanosized SiC is physically dispersed in the matrix in the form of a second phase. SiC second phase compositing further optimized the matrix carrier concentration, resulting in a higher power factor in the service temperature range (the highest value from 28.9 to 31.7 µW cm-1 K-2), and the (ZT)ave from 0.91 to 0.96 compared with the matrix sample. In addition, the SiC second phase effectively enhanced the mechanical properties of composite materials, including flexural strength, microhardness, and modulus. Because of the simultaneous optimization of thermoelectric and mechanical properties, the overall performance of Te-doped Mg3.2Bi1.5Sb0.5-0.05 vol % SiC composite is leveraged to meet special requirements of power generation. It is expected that the addition of SiC should be broadly applicable to address the physical performance in other thermoelectric systems.

2.
Tumori ; : 3008916231221636, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38183180

ABSTRACT

The microenvironment of diffuse large B-cell lymphoma (DLBCL) is composed of various components, including immune cells and immune checkpoints, some of which have been correlated with the prognosis of DLBCL, but their results remain controversial. Therefore, we conducted a systematic review and meta-analysis to investigate the association between the microenvironment and prognosis in DLBCL. We searched PubMed, Web of Science, and EMBASE for relevant articles between 2001 and 2022. Twenty-five studies involving 4495 patients with DLBCL were included in the analysis. This meta-analysis confirmed that high densities of Foxp3+Tregs and PD-1+T cells are good indicators for overall survival (OS) in DLBCL, while high densities of programmed cell death protein ligand1(PD-L1)-positive expression cells and T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3)-positive expression tumor-infiltrating cells (TILs) play a contrary role in OS. Additionally, higher numbers of T-cell intracytoplasmic antigen-1(TIA-1)-positive expression T cells imply better OS and progression-free survival (PFS), while high numbers of lymphocyte activation gene(LAG)-positive expression TILs predict bad OS and PFS. Various non-tumoral cells in the microenvironment play important roles in the prognosis of DLBCL.

3.
Adv Sci (Weinh) ; 11(9): e2303366, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38105421

ABSTRACT

To combat SARS-CoV-2 variants and MERS-CoV, as well as the potential re-emergence of SARS-CoV and spillovers of sarbecoviruses, which pose a significant threat to global public health, vaccines that can confer broad-spectrum protection against betacoronaviruses (ß-CoVs) are urgently needed. A mosaic ferritin nanoparticle vaccine is developed that co-displays the spike receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 Wild-type (WT) strain and evaluated its immunogenicity and protective efficacy in mice and nonhuman primates. A low dose of 10 µg administered at a 21-day interval induced a Th1-biased immune response in mice and elicited robust cross-reactive neutralizing antibody responses against a variety of ß-CoVs, including a series of SARS-CoV-2 variants. It is also able to effectively protect against challenges of SARS-CoV, MERS-CoV, and SARS-CoV-2 variants in not only young mice but also the more vulnerable mice through induction of long-lived immunity. Together, these results suggest that this mosaic 3-RBD nanoparticle has the potential to be developed as a pan-ß-CoV vaccine.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Nanoparticles , Viral Vaccines , Humans , Animals , Mice , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/prevention & control , SARS-CoV-2 , Middle East Respiratory Syndrome Coronavirus/chemistry , Models, Animal
4.
Sci Total Environ ; 904: 166744, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37659528

ABSTRACT

BACKGROUND: Little is known about the associations of exposure to fine particulate matter (PM2.5) and its constituents with ovarian reserve, and the potential susceptible window of exposure remains unclear. METHODS: We performed a retrospective cohort study of 5189 women who attended a fertility center in Hubei, China, during 2019-2022, and estimated concentrations of PM2.5 and its major constituents during the development of follicles (4th-6th month [W1], 0-4th month [W2], 0-6th month [W3]) and 1-year before measurement (W4) based on Tracking Air Pollution in China database. We used multivariable linear regression and logistic regression models to examine the associations of PM2.5 and its constituent exposures with anti-Müllerian hormone (AMH), the preferred indicator of ovarian reserve. RESULTS: We observed significantly decreased AMH levels associated with increasing PM2.5 concentrations, with the percent changes (95 % confidence intervals [CIs]) of 1.99 % (0.24 %-3.71 %) during W1 and 3.99 % (0.74 %-7.15 %) during W4 for per 10 µg/m3 increases in PM2.5.When PM2.5 exposure levels were equal to 50th percentile (32.6-42.3 µg/m3) or more, monotonically decreased AMH levels and increased risks of low AMH were seen with increasing PM2.5 concentrations during W1 and W4 (P < 0.05). Black carbon (BC), ammonium (NH4+), nitrate (NO3-), and organic matter (OM) during W1, and NH4+, NO3-, as well as sulfate (SO42-) during W4 were significantly associated with decreased AMH. Moreover, PM2.5 and SO42- exposures during W4 were positively associated with low AMH. Additionally, the associations were stronger among women aged <35 years, lived in urban regions, or measured AMH in cold-season (P for interaction <0.05). CONCLUSION: PM2.5 and specific chemical components (particularly NH4+, NO3-, and SO42-) exposure during the secondary to antral follicle stage and 1-year before measurement were associated with diminished ovarian reserve (DOR), indicating the adverse impact of PM2.5 and its constituent exposures on female reproductive potential.


Subject(s)
Air Pollutants , Air Pollution , Ovarian Reserve , Female , Humans , Particulate Matter/analysis , Retrospective Studies , Air Pollution/analysis , Fertility , Anti-Mullerian Hormone , China , Air Pollutants/analysis , Environmental Exposure
5.
bioRxiv ; 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37577682

ABSTRACT

The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered as a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease, but was recently found to possess broad-spectrum off-target effects. Here we show that, under physiological conditions, niclosamide acutely potentiates TMEM16A without having any inhibitory effect. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering niclosamide as a TMEM16A inhibitor to treat diseases such as asthma, COPD, and hypertension. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation, shining light on developing specific TMEM16A modulators to treat human diseases.

6.
Clin Lab ; 69(8)2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37560870

ABSTRACT

BACKGROUND: This study aimed to investigate the value of miR-671-5p in multiple myeloma (MM) in diagnostics and prognosis and developed a potential biomarker to improve the prognosis of MM. METHODS: Plasma cells were isolated from bone marrow samples of 80 MM patients, in which miR-671-5p levels were determined. The correlation between miR-671-5p expression with serum creatinine, ß-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, chromosomal abnormalities, and albumin was analyzed. The association between miR-671-5p expression with progression-free survival and overall survival in MM patients was determined. RESULTS: miR-671-5p expression was reduced and predicted an increased risk of MM. miR-671-5p expression was negatively correlated with serum creatinine, ß-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, and chromosomal abnormalities, and positively correlated with albumin. miR-671-5p expression was augmented in complete response patients and overall response rate patients, and differentiated CR and ORR patients from Non-CR and Non-ORR patients. Furthermore, miR-671-5p low expression was associated with unfavorable progression-free survival and overall survival in MM patients. CONCLUSIONS: In a word, miR-671-5p is associated with worsening clinical properties, increased ISS staging, unfavorable chromosomal abnormalities, and poor prognosis in MM patients.


Subject(s)
MicroRNAs , Multiple Myeloma , Humans , MicroRNAs/genetics , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Creatinine , Prognosis , Albumins , Chromosome Aberrations , Lactate Dehydrogenases
7.
Front Public Health ; 11: 1159348, 2023.
Article in English | MEDLINE | ID: mdl-37457253

ABSTRACT

Background: Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. Methods: A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (ß), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Results: Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (ß ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (ß < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when ß ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Conclusion: Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.


Subject(s)
Hearing Loss, Noise-Induced , Noise, Occupational , Occupational Exposure , Humans , Hearing Loss, Noise-Induced/epidemiology , Hearing Loss, Noise-Induced/etiology , Occupational Exposure/adverse effects , Cross-Sectional Studies , Surveys and Questionnaires , Noise, Occupational/adverse effects
8.
Ann Diagn Pathol ; 66: 152165, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37348414

ABSTRACT

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphoma, characterized by a variety of clinicopathological, histomorphological, immunophenotypic, and molecular genetic features. The subtype of DLBCL known as double-expressor lymphoma (DEL) is associated with an adverse prognosis when treated with R-CHOP. Our study aimed to investigate the clinicopathologic features of DEL and the prognostic roles of Myc rearrangement and C-Myc expression in DEL patients. PATIENTS AND METHODS: We conducted a retrospective study of 145 patients who were identified through fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) testing. RESULTS: We found that DEL patients were more likely to have a non-germinal center B-cell (GCB) subtype, stage III/IV disease, and a high International Prognostic Index (IPI) score. Our survival analysis indicated that Myc rearrangement and C-Myc expression were associated with poor prognosis. Although DEL patients with Myc rearrangement exhibited trends towards worse survival compared with patients without Myc rearrangement, the differences were not statistically significant (P = 0.4008). The median overall survival (OS) of DEL patients with ≥70 % C-Myc expression (DEL-C-Mychigh) was 5 months. In the DEL-C-Mychigh group, the non-GCB subtype showed nonsignificant trends towards poorer survival compared with the GCB subtype (P = 0.1042). CONCLUSION: In conclusion, our study shows that a cut-off of ≥70 % for C-Myc expression in DEL patients can improve risk stratification, and suggests that more intensive treatment regimens may be necessary to improve survival in this high-risk population.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Proto-Oncogene Proteins c-myc , Humans , Retrospective Studies , In Situ Hybridization, Fluorescence , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
9.
Photoacoustics ; 31: 100494, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37131996

ABSTRACT

Membrane viscosity is an important property of cell biology, which determines cellular function, development and disease progression. Various experimental and computational methods have been developed to investigate the mechanics of cells. However, there have been no experimental measurements of the membrane viscosity at high-frequencies in live cells. High frequency measurements are important because they can probe viscoelastic effects. Here, we investigate the membrane viscosity at gigahertz-frequencies through the damping of the acoustic vibrations of gold nanoplates. The experiments are modeled using a continuum mechanics theory which reveals that the membranes display viscoelasticity, with an estimated relaxation time of ca. 5.7 + 2.4 / - 2.7 ps. We further demonstrate that membrane viscoelasticity can be used to differentiate a cancerous cell line (the human glioblastoma cells LN-18) from a normal cell line (the mouse brain microvascular endothelial cells bEnd.3). The viscosity of cancerous cells LN-18 is lower than that of healthy cells bEnd.3 by a factor of three. The results indicate promising applications of characterizing membrane viscoelasticity at gigahertz-frequency in cell diagnosis.

10.
Org Lett ; 25(20): 3607-3610, 2023 May 26.
Article in English | MEDLINE | ID: mdl-37166363

ABSTRACT

An enantioselective metal-free hydrogenation of hydrazones has been realized successfully using chiral boranes as catalysts, producing a range of optically active hydrazines in 87-99% yields with 75-93% ee's. The bulky 2,2,6,6-tetramethylpiperidinyl moiety was found to be essential for achieving the high enantioselectivities.

11.
Proc Natl Acad Sci U S A ; 120(12): e2218825120, 2023 03 21.
Article in English | MEDLINE | ID: mdl-36917666

ABSTRACT

Interferons (IFNs) and the products of interferon-stimulated genes (ISGs) play crucial roles in host defense against virus infections. Although many ISGs have been characterized with respect to their antiviral activity, their target specificities and mechanisms of action remain largely unknown. Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is linked to several human malignancies. Here, we used the genetically and biologically related virus, murine gammaherpesvirus 68 (MHV-68) and screened for ISGs with anti-gammaherpesvirus activities. We found that overexpression of RNF213 dramatically inhibited MHV-68 infection, whereas knockdown of endogenous RNF213 significantly promoted MHV-68 proliferation. Importantly, RNF213 also inhibited KSHV de novo infection, and depletion of RNF213 in the latently KSHV-infected iSLK-219 cell line significantly enhanced lytic reactivation. Mechanistically, we demonstrated that RNF213 targeted the Replication and Transcription Activator (RTA) of both KSHV and MHV-68, and promoted the degradation of RTA protein through the proteasome-dependent pathway. RNF213 directly interacted with RTA and functioned as an E3 ligase to ubiquitinate RTA via K48 linkage. Taken together, we conclude that RNF213 serves as an E3 ligase and inhibits the de novo infection and lytic reactivation of gammaherpesviruses by degrading RTA through the ubiquitin-proteasome pathway.


Subject(s)
Gammaherpesvirinae , Herpesviridae Infections , Herpesvirus 8, Human , Immediate-Early Proteins , Humans , Adenosine Triphosphatases/metabolism , Gammaherpesvirinae/genetics , Gene Expression Regulation, Viral , Herpesviridae Infections/genetics , Herpesvirus 8, Human/metabolism , Immediate-Early Proteins/metabolism , Proteasome Endopeptidase Complex/metabolism , Trans-Activators/metabolism , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Virus Latency/genetics , Virus Replication
12.
Nat Cancer ; 4(3): 382-400, 2023 03.
Article in English | MEDLINE | ID: mdl-36894639

ABSTRACT

Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates to upregulate PD-L1. Multivalency from both the specific and promiscuous interactions between IRF1 and KAT8 is required for condensate formation. KAT8-IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8-IRF1 condensate formation, we identified the 2142-R8 blocking peptide, which disrupts KAT8-IRF1 condensate formation and consequently inhibits PD-L1 expression and enhances antitumor immunity in vitro and in vivo. Our findings reveal a key role of KAT8-IRF1 condensates in PD-L1 regulation and provide a competitive peptide to enhance antitumor immune responses.


Subject(s)
B7-H1 Antigen , Programmed Cell Death 1 Receptor , Humans , Cell Line, Tumor , B7-H1 Antigen/genetics , Programmed Cell Death 1 Receptor/metabolism , Interferon-gamma/genetics , Interferon-gamma/pharmacology , Immunotherapy , Histone Acetyltransferases/metabolism , Interferon Regulatory Factor-1/genetics , Interferon Regulatory Factor-1/metabolism
13.
Sci Total Environ ; 854: 158606, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36089043

ABSTRACT

Global concern over microplastics (MPs) is increasing because of the potential threat these substances pose to ecosystem and human health. Disposable cups, frequently used as containers of beverages, are typically made of plastic or plastic-coated paper. The release of MPs from disposable cups during use may provide a direct exposure pathway for humans. In this study, the MP release capacities of 90 batches of commercial disposable cups, including polyethylene (PE)-coated paper cups, polypropylene (PP) cups, and polystyrene (PS) cups, were investigated under daily use conditions, and the properties of released MP particles are characterized with Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The MPs release into containing beverages is detected for each of the tested cups in this study. The released MPs particles are in irregular shapes and dominantly smaller than 20 µm. The quantities of released MPs are in the range of 675-5984, 781-4951, and 838-5215 particles/L for PE-coated paper cups, PP cups and PS cups, respectively, when containing pure water at 95 °C for 20 min. No significant difference in the quantity of MP released is observed among the three types of the cups in the experimental conditions. High temperature is found to promote the release of MPs from disposable cups. The MP release is notable when the cups are used for a second time, although at a slightly lower level than the first use. Acidic carbonated beverages obviously enhance MP release from PE-coated cups over that of ultrapure water.


Subject(s)
Microplastics , Water Pollutants, Chemical , Humans , Plastics/chemistry , Ecosystem , Polypropylenes/analysis , Polystyrenes , Water , Polyethylene , Water Pollutants, Chemical/analysis , Environmental Monitoring
14.
J Clin Endocrinol Metab ; 108(3): 736-744, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36205019

ABSTRACT

CONTEXT: Impairment of immune and inflammatory homeostasis is reported to be one of the causal factors of diabetes. However, the association of complement C3 levels with incident diabetes in humans remains unclear. OBJECTIVE: This study aimed to examine the association between C3 levels and incident type 2 diabetes mellitus (T2DM), and further explore the potential mediating role of body mass index (BMI) in C3-T2DM associations. METHODS: We determined serum C3 levels of 2662 nondiabetic middle-aged and elderly (64.62 ± 7.25 years) individuals from the Dongfeng-Tongji cohort at baseline. Cox regression was employed to examine the incidence of T2DM in relationship to C3 levels during 10 years of follow-up. Mediation analysis was further applied to assess potential effect of BMI on the C3-T2DM associations. RESULTS: Overall, 711 (26.7%) participants developed T2DM during 23 067 person-years of follow-up. Higher serum C3 was significantly associated with higher risk of incident T2DM after full adjustment (HR [95% CI] = 1.16 [1.05, 1.27]; per SD higher). Compared with the first quartile of C3 levels, the HR in the fourth quartile was 1.52 (95% CI = [1.14, 2.02]; Ptrend = 0.029). Robust significant linear dose-response relationship was observed between C3 levels and BMI (Poverall < 0.001, Pnonlinear = 0.96). Mediation analyses indicated that BMI might mediate 41.0% of the associations between C3 and T2DM. CONCLUSION: The present prospective study revealed that C3 could be an early biomarker for incident T2DM, and that BMI might play a potential mediating role in the C3-T2DM associations, which provided clues for the pathogenesis of diabetes.


Subject(s)
Body Mass Index , Complement C3 , Diabetes Mellitus, Type 2 , Aged , Humans , Middle Aged , Complement C3/chemistry , Complement C3/metabolism , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Follow-Up Studies , Incidence , Prospective Studies , Risk Factors
15.
Nat Hum Behav ; 7(2): 200-210, 2023 02.
Article in English | MEDLINE | ID: mdl-36482078

ABSTRACT

Cooking is practiced worldwide and is associated with multiple social, economic and environmental factors; thus, understanding cooking-related health effects would have broad public health implications. Here, we show that after an average 9.9 years of follow-up for 510,106 Chinese adults, always cooking with clean fuels was associated with lower risks of all-cause (0.90 [95% confidence interval 0.87-0.93]; P = 1.39 × 10-9), cardiovascular (0.83 [0.78-0.87]; P = 6.83 × 10-11) and respiratory (0.88 [0.79-0.99]; P = 0.026) mortality compared with non-cooking, of which 50.1% (14.5-85.6%) to 66.0% (38.5-85.8%) could be attributed to increased household physical activity. The mortality risks decreased with extended duration of cooking with clean fuels in dose-response manners, with the lowest hazard ratios of 0.74 (0.68-0.80; P = 1.20 × 10-13) for all-cause and 0.62 (0.55-0.71; P = 3.15 × 10-12) for cardiovascular mortality among never-smokers reported over 25 years of cooking. Our findings suggest lower future mortality risks may be gained only when cooking with clean fuels.


Subject(s)
Air Pollution, Indoor , Family Characteristics , Adult , Humans , Prospective Studies , Cooking
16.
Protein Expr Purif ; 203: 106199, 2023 03.
Article in English | MEDLINE | ID: mdl-36372201

ABSTRACT

Chitosanases hydrolyze chitosan into chitooligosaccharides (COSs) with various biological activities, which are widely employed in many areas including plant disease management. In this study, the novel chitosanase AqCsn1 belonging to the glycoside hydrolase family 46 (GH46) was cloned from Aquabacterium sp. A7-Y and heterologously expressed in Escherichia coli BL21 (DE3). AqCsn1 displayed the highest hydrolytic activity towards chitosan with 95% degree of deacetylation at 40 °C and pH 5.0, with a specific activity of 13.18 U/mg. Product analysis showed that AqCsn1 hydrolyzed chitosan into (GlcN)2 and (GlcN)3 as the main products, demonstrating an endo-type cleavage pattern. Evaluation of antagonistic activity showed that the hydrolysis products of AqCsn1 suppress the mycelial growth of Magnaporthe oryzae and Phytophthora sojae in a concentration-dependent manner, and the inhibition rate of P. sojae reached 39.82% at a concentration of 8 g/L. Our study demonstrates that AqCsn1 and hydrolysis products with a low degree of polymerization might have potential applications in the biological control of agricultural diseases.


Subject(s)
Chitosan , Chitosan/pharmacology , Polymerization , Chitin , Oligosaccharides/pharmacology , Glycoside Hydrolases/genetics , Glycoside Hydrolases/chemistry , Hydrolysis , Escherichia coli/genetics
17.
Acta Pharmaceutica Sinica ; (12): 721-728, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965621

ABSTRACT

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

18.
Int J Behav Nutr Phys Act ; 19(1): 151, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36514169

ABSTRACT

BACKGROUND: The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear. METHODS: The present study included 366,566 participants (aged 40-69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes. RESULTS: During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86-0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78-0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0-150 min/week; VPA, 0-75 min/week), those performing 150-300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79-0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63-0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA. CONCLUSIONS: Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.


Subject(s)
Cardiovascular Diseases , Humans , Adult , Prospective Studies , Exercise , Proportional Hazards Models , United Kingdom/epidemiology
19.
Nature ; 611(7934): 180-187, 2022 11.
Article in English | MEDLINE | ID: mdl-36289327

ABSTRACT

Bestrophin-2 (BEST2) is a member of the bestrophin family of calcium-activated anion channels that has a critical role in ocular physiology1-4. Here we uncover a directional permeability of BEST2 to glutamate that heavily favours glutamate exit, identify glutamine synthetase (GS) as a binding partner of BEST2 in the ciliary body of the eye, and solve the structure of the BEST2-GS complex. BEST2 reduces cytosolic GS activity by tethering GS to the cell membrane. GS extends the ion conducting pathway of BEST2 through its central cavity and inhibits BEST2 channel function in the absence of intracellular glutamate, but sensitizes BEST2 to intracellular glutamate, which promotes the opening of BEST2 and thus relieves the inhibitory effect of GS. We demonstrate the physiological role of BEST2 in conducting chloride and glutamate and the influence of GS in non-pigmented ciliary epithelial cells. Together, our results reveal a novel mechanism of glutamate release through BEST2-GS.


Subject(s)
Bestrophins , Glutamate-Ammonia Ligase , Glutamic Acid , Glutamine , Bestrophins/metabolism , Epithelial Cells/metabolism , Glutamate-Ammonia Ligase/metabolism , Glutamic Acid/metabolism , Glutamine/metabolism , Ciliary Body/metabolism , Cell Membrane/metabolism , Chlorides/metabolism
20.
Opt Express ; 30(13): 22885-22900, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-36224979

ABSTRACT

Functional tunability, environmental adaptability, and easy fabrication are highly desired properties in metasurfaces. Here we provide a tunable bilayer metasurface composed of two stacked identical dielectric magnetic mirrors. The magnetic mirrors are excited by the interaction between the interference of multipoles of each cylinder and the lattice resonance of the periodic array, which exhibits nonlocal electric field enhancement near the interface and high reflection. We achieve the reversible conversion between high reflection and high transmission by manipulating the interlayer coupling near the interface between the two magnetic mirrors. Controlling the interlayer spacing leads to the controllable interlayer coupling and scattering of meta-atom. The magnetic mirror effect boosts the interlayer coupling when the interlayer spacing is small. Furthermore, the high transmission of the bilayer metasurface has good robustness due to the meta-atom with interlayer coupling can maintain scattering suppression against positional perturbation. This work provides a straightforward method to design tunable metasurface and sheds new light on high-performance optical switches applied in communication and sensing.

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