Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 869
Filter
1.
ACS Macro Lett ; 10(10): 1300-1305, 2021 Oct 19.
Article in English | MEDLINE | ID: mdl-35549051

ABSTRACT

Self-assembly of chiral block copolymers (BCPs*) can give rise to ordered chiral nanostructures, that is, a helical phase (H* phase), via chirality transfer from the molecular level to mesoscale. In the present work, we reported the self-assembly of BCPs* under one-dimensional spatial confinement. The morphological dependence of self-assembled BCPs* on the molecular weights and the film thickness was investigated. As chiral nanostructures, the H* phase can be formed in bulk, nonchiral nanostructures that were observed in the thin films. Also, the topology effect of self-assembly of BCPs* was examined. The self-assembly of BCPs* with a star-shaped topology exhibited a distinct morphology compared with that of linear BCPs*. The present work provides new insight into the chirality transfer of macromolecules under spatial confinement.

2.
RSC Adv ; 9(36): 20786-20795, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-35515523

ABSTRACT

The QM/MM method is employed to investigate the photophysical mechanism of two dinuclear copper iodide complexes with thermally activated delayed fluorescence (TADF). The S1-T1 energy differences (ΔE ST) in these two complexes are small enough so that repopulating the S1 state from T1 becomes energetically allowed. Both forward and reverse intersystem crossing (ISC and rISC) processes are much faster than the corresponding radiative fluorescence and phosphorescence processes [k ISC (108 s-1) > k F r (106 s-1), k rISC (105 s-1) > k P r (103 s-1)]. The faster rISC process than the phosphorescence emission enables TADF. Moreover, the diphosphine ligands are found to play an important role in regulating the electronic structures and thereto the radiative and nonradiative rate constants. The present work rationalizes experimental phenomena and helps understand the intrinsic luminescence properties. The obtained insights could be useful for tuning the luminescence performance of dicopper-based luminescence materials.

3.
Front Neurosci ; 16: 639656, 2022.
Article in English | MEDLINE | ID: mdl-35495024

ABSTRACT

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.

4.
Artif Organs ; 2022 May 02.
Article in English | MEDLINE | ID: mdl-35491962

ABSTRACT

OBJECTIVE: To evaluate whether septic shock patients with pulmonary infection and life-threatening hypoxemia can benefit from V-V ECMO. METHODS: Retrospective clinical data analysis on patients who suffered septic shock with pulmonary infection, categorized into V-V ECMO and control groups. The propensity score matching (PSM) method was used to screen patients matched for age, gender, and disease severity. The primary outcome was 30- and 90-day mortality after diagnosis of septic shock. RESULTS: After PSM, 31 pairs of patients were enrolled in this study, and there were no significant differences between the two groups in terms of gender, age, chronic disease, acute physiological and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. Within 28 days after the diagnosis of septic shock, the median time of renal replacement therapy-free days was longer in the V-V ECMO group than in the control group (27 days vs. 9 days; p = 0.044). Kaplan-Meier analysis showed that 30-day mortality was lower in the V-V ECMO group than in the control group (38.7% vs. 61.3%; HR 0.488; 95% CI 0.240-0.992; p = 0.043, by log-rank test); 90-day mortality was not significantly different between the two groups (51.6% vs. 67.7%, p = 0.097). CONCLUSION: Patients receiving V-V ECMO support had lower 30-day mortality and faster recovery of renal function within 28 days compared with those receiving conventional therapy. However, V-V ECMO did not improve 90-day survival in septic shock patients with pulmonary infection.

5.
Ann Clin Transl Neurol ; 9(5): 747-755, 2022 May.
Article in English | MEDLINE | ID: mdl-35482004

ABSTRACT

BACKGROUND: Biallelic POLR3B mutations cause a rare hypomyelinating leukodystrophy. De novo POLR3B heterozygous mutations were recently associated with afferent ataxia, spasticity, variable intellectual disability, and epilepsy, and predominantly demyelinating sensorimotor peripheral neuropathy. METHODS: We performed whole-exome sequencing (WES) of DNA samples from 804 Charcot-Marie-Tooth (CMT) cases that could not be genetically diagnosed by DNA-targeted resequencing microarray using next-generation sequencers. Using WES data, we analyzed the POLR3B mutations and confirmed their clinical features. RESULTS: We identified de novo POLR3B heterozygous missense mutations in two patients. These patients presented with early-onset demyelinating sensorimotor neuropathy without ataxia, spasticity, or cognitive impairment. Patient 1 showed mild cerebellar atrophy and spinal cord atrophy on magnetic resonance imaging and eventually died of respiratory failure in her 50s. We classified these mutations as pathogenic based on segregation studies, comparison with control database, and in silico analysis. CONCLUSION: Our study is the third report on patients with demyelinating CMT harboring heterozygous POLR3B mutations and verifies the pathogenicity of POLR3B mutations in CMT. Although extremely rare in our large Japanese case series, POLR3B mutations should be added to the CMT-related gene panel for comprehensive genetic screening, particularly for patients with early-onset demyelinating CMT.


Subject(s)
Charcot-Marie-Tooth Disease , Ataxia , Atrophy , Charcot-Marie-Tooth Disease/genetics , Female , Humans , Japan , Mutation , Phenotype , RNA Polymerase III/genetics
6.
Front Genet ; 13: 855355, 2022.
Article in English | MEDLINE | ID: mdl-35480301

ABSTRACT

Gastric cancer is a kind of gastrointestinal tumor with high morbidity and mortality. Finding effective methods for early diagnosis and treatment of gastric cancer has important significance and application prospects. MicroRNAs without protein coding potential affect the occurrence and development of gastric cancer. This study aims to explore the biological function and mechanism of microRNA-107 (miR-107) in gastric cancer. The results show that miR-107 is low expressed in gastric cancer, while TRIAP1 is highly expressed; the overexpression of miR-107 can inhibit the progression of gastric cancer in vivo and in vitro, while the overexpression plasmid of TRIAP1 can restore the miR-107 mimic-induced cell proliferation and metastasis inhibition, and the small interfering RNA of TRIAP1 can inhibit the cell proliferation and invasion induced by miR-107 inhibitor. In conclusion, the results of this study show that miR-107 can inhibit the proliferation of gastric cancer in vivo and in vitro by targeting TRIAP1.

7.
Front Neurol ; 13: 711209, 2022.
Article in English | MEDLINE | ID: mdl-35432178

ABSTRACT

Objective: This study aimed to explore the use of the Omaha System in rehabilitation and nursing methods and the effects on patients within the community who had experienced stroke and previous falls. Methods: This study enrolled 42 patients who had experienced stroke and previous falls and had returned to the community after being discharged from the Department of Neurology and Rehabilitation of the Affiliated Hospital of Nanchang University from January to July 2018. The patients were randomly divided into two groups: an experimental group (n = 21) and a control group (n = 21). Patients in the control group received routine community rehabilitation care, and patients in the experimental group received community rehabilitation care on the basis of the Omaha System. Intervention lasted for 1 year. The Omaha outcome score, the ability to perform activities of daily living (ADL) (measured via the Modified Barthel Index [MBI]), and the incidence of falls for each group were compared before and after the intervention. Results: After 1 year of intervention, the Omaha outcome score and MBI of both groups were higher than before; the Omaha outcome score and MBI of the experimental group were higher than those of the control group; the differences were statistically significant (P < 0.05). No fall occurred in either of the two groups. Conclusion: The Omaha System can comprehensively evaluate the health problems of patients, guide nursing intervention, and quantitatively evaluate the effect of nursing intervention; it is therefore worthy of promotion.

8.
ACS Appl Mater Interfaces ; 14(16): 18043-18052, 2022 Apr 27.
Article in English | MEDLINE | ID: mdl-35420773

ABSTRACT

Multimodal imaging-guided combinational phototherapies triggered by a single near-infrared (NIR) laser are highly desirable. However, their development is still a big challenge. Herein, we have developed an "acceptor-donor-acceptor'-donor-acceptor" structured organic phototheranostics (Y16-Pr) with strong light-harvesting ability in the NIR region. After being modified with polyethylene glycol (PEG), the obtained biocompatible nanoparticles (Y16-Pr-PEG NPs) could conduct NIR-II fluorescence imaging (FLI) and photoacoustic imaging (PAI) and perform photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Notably, Y16-Pr-PEG NPs showed an impressive photothermal conversion efficiency (PCE) of 82.4% under 808 nm laser irradiation. The irradiated NPs could also produce hydroxyl radicals (•OH) and singlet oxygen (1O2) for type I and type II PDT, respectively. In vivo and in vitro experiments revealed that the Y16-Pr-PEG NPs significantly inhibit tumor cell growth without apparent toxic side effects under laser irradiation. Overall, the single-laser-triggered multifunctional phototheranostic Y16-Pr-PEG NPs can achieve NIR-II FLI/PAI-guided synergistic PTT/PDT against tumors.


Subject(s)
Nanoparticles , Photoacoustic Techniques , Photochemotherapy , Cell Line, Tumor , Nanoparticles/therapeutic use , Optical Imaging , Photoacoustic Techniques/methods , Photochemotherapy/methods , Phototherapy , Theranostic Nanomedicine/methods
9.
Exp Cell Res ; 416(1): 113149, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35405116

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as novel players in cancer metabolism. lncRNA small nucleolar RNA host gene 7 (SNHG7) plays an oncogenic role in prostate cancer (PCa). However, the role and mechanism of SNHG7 in PCa metabolism remain largely undefined. METHODS: A cohort of 30 PCa tumors and their counterparts were collected. qRT-PCR was employed to detect target gene expression and RNA stability. CCK-8 assay was used to assess cell viability. N6-methyladenosine (m6A) level was measured by a commercial kit. Cell glycolysis was evaluated by measuring glucose uptake, lactate, ATP production and Extracellular acidification rate (ECAR). Bioinformatics analysis and RNA immunoprecipitation (RIP) assay were used to verify the interactions among SNHG7, serine/arginine-rich splicing factor 1 (SRSF1) and c-Myc. RESULTS: SNHG7 and c-Myc were highly expressed in PCa tissues and cells. Methyltransferase-like 3 (METTL3)-mediated m6A modification of SNHG7 and enhanced its stability. Silencing of SNHG7 suppressed proliferation and glycolysis in PCa cells. Mechanistically, SNHG7 regulated c-Myc via interacting with SRSF1. Gain- and loss-of function experiments revealed that SNHG7 promoted glycolysis via SRSF1/c-Myc axis in PC-3 and DU-145 cells. CONCLUSION: METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in PCa via SRSF1/c-Myc axis and inspires the understanding of m6A roles in lncRNA metabolism and tumor progression.


Subject(s)
MicroRNAs , Prostatic Neoplasms , RNA, Long Noncoding , Carcinogenesis/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Glycolysis/genetics , Humans , Male , Methyltransferases/genetics , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism
10.
J Oncol ; 2022: 1192368, 2022.
Article in English | MEDLINE | ID: mdl-35401747

ABSTRACT

Objective: To investigate the combined application value of magnetic resonance imaging (MRI) combined with serum alpha-fetoprotein (AFP)-L3 and Golgi protein (GP)-73 in the diagnosis of primary liver cancer. Methods: The data of 200 patients with suspected liver cancer admitted to our hospital from February 2020 to February 2021 were retrospectively analyzed, and they were randomly divided into an experimental group and a control group, with 100 cases in each group. The experimental group received a combined detection of MRI with serum AFP-L3 and GP-73, and the control group adopted traditional diagnostic methods (spiral computed tomography and serum AFP). The diagnostic yields of the two groups were compared. Surgical resection was performed after the diagnosis of primary liver cancer, and the correlation between the efficacy and combined detection of MRI with serum AFP-L3 and GP-73 levels was analyzed. Results: The two groups presented comparable general information (P >0.05). The surgical results showed 160 cases of primary liver cancer, including 75 cases in the experimental group and 85 cases in the control group, and 40 cases of benign liver lesions. The diagnostic accuracy of the experimental group (73/75, 95%) was significantly higher than that of the control group (76/85, 86%) (P < 0.05). The serum levels of AFP-L3, GP-73, and AFP in patients with primary liver cancer were remarkably decreased after surgery (P < 0.001). The preoperative and postoperative AFP-L3, GP-73, and AFP levels of patients with primary liver cancer were significantly higher than those of patients with benign liver lesions. The AUC (95% CI) for the combined detection of MRI and serum AFP-L3 and GP-73 levels in patients with surgically confirmed primary liver cancer was 0.747 (0.619-0.874). Conclusion: MRI combined with serum AFP-L3 and GP-73 presents favorable diagnostic efficiency in the diagnosis of primary liver cancer, which is worthy of clinical application.

11.
Phytomedicine ; 100: 154049, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35397287

ABSTRACT

BACKGROUND: Scutellariae Radix (SR), the root of Scutellaria baicalensis Georgi, and SR flavonoids have antifibrotic activities. It remains obscure, however, amongst SR aqueous extract (SRA), SR methanolic extract (SRM) and five major SR flavonoids (baicalein, baicalin, wogonoside, wogonin and oroxyloside), which ones are the most promising antifibrotics and what their mechanisms are. PURPOSE: To compare the antifibrotic activities of SR extracts and flavonoids, and the proteomic signatures of selected SR extract and flavonoid, versus IN1130 phosphate, an antifibrotic positive control (abbreviated as IN1130), in TGF-ß1-induced in vitro model of fibrosis in NRK-49F renal fibroblasts. METHODS: Isobaric labelling-based mass spectrometry was used for proteomic studies. Differentially expressed proteins were further analyzed using Gene Ontology annotation enrichment, protein-protein interaction network analysis and pathway analysis. Selected proteins of interest were validated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Baicalein was the SR flavonoid with the best efficacy-toxicity ratio. SRM contained 8-fold more flavonoids and was more potently antifibrotic than SRA. Proteomic analysis of cells treated by TGF-ß1, with or without baicalein (40 and 80 µM), SRM (40 and 80 µg/ml) and IN1130 (1 µM) suggested that baicalein, SRM and IN1130 all repressed TGF-ß1-induced ribosomal proteins in cell lysates, while baicalein and SRM, but not IN1130, regulated the intracellular lysosome pathway; secretomic analysis suggested that 40 and 80 µg/ml SRM and 80 µM baicalein, but not IN1130 and 40 µM baicalein increased ribosomal proteins in conditioned media, whereas only baicalein regulated the lysosome pathway. ELISA verified secretomic findings that baicalein, SRM and IN1130 repressed TGF-ß1-induced PAI-1 (Serpine1), Plod2, Ctgf (Ccn2), Ccl2 and Ccl7; baicalein and IN1130, but not SRM, reversed TGF-ß1-induced Cyr61 (Ccn1) and Tsku; only baicalein reversed TGF-ß1 repression of Mmp3; only IN1130 reversed TGF-ß1-repressed Nov (Ccn3). ELISA validated cell-lysate proteomic findings that baicalein, SRM and IN1130 all reversed TGF-ß1-induced Enpp1; only IN1130 reversed TGF-ß1-induced Impdh2 and Sqstm1 and TGF-ß1-repressed Aldh3a1. Baicalein and SRM induced Ccdc80, while only baicalein induced Tfrc. CONCLUSION: Baicalein, SRM and IN1130 repress TGF-ß1-induced fibrogenesis in renal fibroblasts by regulating overlapping protein targets and biological pathways. Our findings offer a comprehensive view of shared, drug- and dose-specific pharmacological and toxicological mechanisms and provide a valuable resource for further research and development of more efficacious and safer antifibrotics.


Subject(s)
Flavanones , Scutellaria baicalensis , Flavanones/pharmacology , Flavonoids/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Proteomics , Ribosomal Proteins , Scutellaria baicalensis/chemistry , Transforming Growth Factor beta1
12.
Immunopharmacol Immunotoxicol ; : 1-8, 2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35352617

ABSTRACT

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common lymphatic tumor in clinic. LncRNAs were reported to play a regulatory role in many cancers, including DLBCL. This study focused on the roles of NEAT1 in DLBCL. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to detect mRNA expression. StarBase as well as TargetScan was used to predict targeting relationships, which was confirmed by the Dual Luciferase Reporter Assay and RNA pull-down assay. Cell Counting Kit 8 (CCK-8) were applied to measure cell viability. Flow cytometry assay was applied to detect cell apoptosis. Western blotting assay was conduct to determine protein expression. Lactate dehydrogenase (LDH) release assay were applied to evaluated cell cytotoxicity. RESULTS: NEAT1 was overexpressed in DLBCL patients. Knockdown of NEAT1 reduced the viability while enhanced the apoptosis of tumor cells. However, overexpression of NEAT1 exhibited an opposite effect. miR-495-3p was a target of NEAT1 and was decreased in DLBCL cells. However, inhibiting miR-495-3p reversed the effect of NEAT1 knock-down on DLBCL cells and induced the malignant behaviors of DLBCL cells. Moreover, NEAT1 functioned as a sponge of miR-495-3p to upregulate PD-L1. CONCLUSION: Our study demonstrated that a NEAT1/miR-495-3p/PD-L1 axis regulated the development of DLBCL. Therefore, NEAT1 may be a potential biomarker for DLBCL.

13.
Euro Surveill ; 27(10)2022 03.
Article in English | MEDLINE | ID: mdl-35272744

ABSTRACT

BackgroundThe Delta variant of SARS-CoV-2 had become predominant globally by November 2021.AimWe evaluated transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China.MethodsData on confirmed COVID-19 cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May and June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated. We also evaluated the association of vaccination with viral load and transmission.ResultsWe identified 167 patients infected with the Delta variant in the Guangdong outbreak. Mean estimates of latent and incubation period were 3.9 days and 5.8 days, respectively. Relatively higher viral load was observed in infections with Delta than in infections with wild-type SARS-CoV-2. Secondary attack rate among close contacts of cases with Delta was 1.4%, and 73.1% (95% credible interval (CrI): 32.9-91.4) of the transmissions occurred before onset. Index cases without vaccination (adjusted odds ratio (aOR): 2.84; 95% CI: 1.19-8.45) or with an incomplete vaccination series (aOR: 6.02; 95% CI: 2.45-18.16) were more likely to transmit infection to their contacts than those who had received the complete primary vaccination series.DiscussionPatients infected with the Delta variant had more rapid symptom onset compared with the wild type. The time-varying serial interval should be accounted for in estimation of reproduction numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , China/epidemiology , Humans , Retrospective Studies , SARS-CoV-2/genetics
14.
J Integr Plant Biol ; 64(5): 979-994, 2022 May.
Article in English | MEDLINE | ID: mdl-35274464

ABSTRACT

Plant hormone abscisic acid (ABA) plays an indispensable role in the control of leaf senescence, during which ABA signaling depends on its biosynthesis. Nevertheless, the role of ABA transport in leaf senescence remains unknown. Here, we identified two novel RING-box protein-encoding genes UBIQUITIN LIGASE of SENESCENCE 1 and 2 (ULS1 and ULS2) involved in leaf senescence. Lack of ULS1 and ULS2 accelerates leaf senescence, which is specifically promoted by ABA treatment. Furthermore, the expression of senescence-related genes is significantly affected in mature leaves of uls1/uls2 double mutant (versus wild type (WT)) in an ABA-dependent manner, and the ABA content is substantially increased. ULS1 and ULS2 are mainly expressed in the guard cells and aging leaves, and the expression is induced by ABA. Further RNA-seq and quantitative proteomics of ubiquitination reveal that ABA transporter ABCG40 is highly expressed in uls1/uls2 mutant versus WT, though it is not the direct target of ULS1/2. Finally, we show that the acceleration of leaf senescence, the increase of leaf ABA content, and the promotion of stomatal closure in uls1/usl2 mutant are suppressed by abcg40 loss-of-function mutation. These results indicate that ULS1 and ULS2 function in feedback inhibition of ABCG40-dependent ABA transport during ABA-induced leaf senescence and stomatal closure.

15.
PeerJ ; 10: e13023, 2022.
Article in English | MEDLINE | ID: mdl-35265398

ABSTRACT

Background: Myxosporean diversity is a hot topic since they are difficult to accurately identify and classify. Many Myxobolus parasites have been named as Myxobolus koi because of their similar morphological features with the species originally reported. However, the distinctions in fine morphological features, host specificity, and molecular data have given rise to the attention of researchers. Methods: The classical morphometric and histological methods were used to describe the Myxobolus dajiangensis n. sp. in morphology. The common techniques in modern molecular biology and the methods of phylogenetic analyses were combined to identify the species. Results: Plasmodia of interlamellar-vascular type were found in the vascular network of gill lamellae. Mature myxospores of M. dajiangensis n. sp. were elongated and pyriform from the frontal view. The myxospores were 14.8 ± 0.4 (13.9-15.6) µm in length, 8.0 ± 0.5 (7.2-9.1) µm in width, and 5.5 µm in thickness. The two polar capsules were pyriform and slightly different in length. The length of the larger polar capsules was 8.0 ± 0.4 (7.1-8.8) µm, and it was 7.4 ± 0.4 (6.1-8.0) µm for the smaller ones. The width of both polar capsules was 2.5 ± 0.2 (2.0-3.2) µm. The polar filaments within the polar capsules were each coiled nine to 11 turns. Comparative analysis of both the morphological and molecular data between the present speices and other similar species revealed that the present species is a novel species, Myxobolus dajiangensis n. sp. Also, M. koi (FJ710800) was misidentified and the congener with M. dajiangensis n. sp., depending on the secondary structures of SSU rRNA and phylogenetic analysis. Moreover, the cryptic species existed in the M. koi parasites.

16.
Invest Ophthalmol Vis Sci ; 63(3): 7, 2022 03 02.
Article in English | MEDLINE | ID: mdl-35262733

ABSTRACT

Purpose: Current treatments for diabetic retinopathy (DR) have considerable limitations, emphasizing the need for new therapeutic options. The effect of leukocyte cell-derived chemotaxin 2 (LECT2) on diabetes-induced blood-retinal barrier impairment and the possible underlying mechanism were investigated both in vivo and in vitro. Methods: Twenty diabetic and 22 nondiabetic eyes were included in this study. Additionally, we established a streptozotocin-induced diabetic mouse model and observed vascular leakage in mice treated with or without recombinant LECT2 (rLECT2) intravitreal injection (40 µg/mL, 1 µL). The levels of LECT2 and interendothelial junction proteins (ZO1, VE-cadherin, and occludin) were analyzed by western blot and/or immunofluorescence. Endothelial junctions in mouse retinas were observed by transmission electron microscopy (TEM). Moreover, confluent human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated (0-72 hours) with glucose (0 or 30 mM) in the presence or absence of rLECT2 (40-360 ng/mL). After treatment, intact cell monolayers were monitored for permeability to 40-kD FITC-dextran. Interendothelial junction targets and Tie2/Akt/mTOR signaling pathway components were investigated by western blot. Results: In diabetic human and mouse retinas and high-glucose (30 mM)-treated HRMECs and HUVECs, the levels of LECT2 and interendothelial junction proteins were decreased. rLECT2 treatment (80 ng/mL) significantly attenuated the hyperglycemia-induced reduction in endothelial cell barrier function and inhibited the migration and tube formation of HRMECs and HUVECs. In addition, rLECT2 increased the levels of interendothelial junction proteins via activation of the Tie2/Akt/mTOR signaling pathway. Furthermore, intravitreal rLECT2 injections increased the levels of interendothelial junction proteins and reversed diabetes-induced junction disruption. Conclusions: rLECT2 can increase the levels of interendothelial tight junction proteins through activation of the Tie2/Akt/mTOR signaling pathway and can ameliorate inner blood-retinal barrier impairment secondary to diabetes. LECT2 might be a potential target to prevent the progression of DR.


Subject(s)
Blood-Retinal Barrier , Diabetes Mellitus , Diabetic Retinopathy , Intercellular Signaling Peptides and Proteins , Animals , Diabetes Mellitus/metabolism , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/metabolism , Glucose/pharmacology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intercellular Signaling Peptides and Proteins/pharmacology , Mice , Proto-Oncogene Proteins c-akt/metabolism , Receptor, TIE-2/metabolism , Recombinant Proteins/pharmacology , Retinal Vessels/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
17.
One Health ; 14: 100376, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35252529

ABSTRACT

Hepatitis E virus (HEV) causes infections in humans and animals. HEV have been identified in pig farms, markets and swine workers, but studies with parallel observations along the poultry and pork supply chains remains limited. This study aimed to characterize HEV infection risks in workers along the meat supply chain. Two rounds of cross-sectional surveys were performed among swine and poultry workers in pig and poultry farms, slaughterhouses, wholesale and retail live poultry markets, live pig markets and pork markets. Human sera from the workers and the general population were collected and tested for HEV specific IgM/IgG antibodies by commercial indirect-ELISA test kits. Risk factors of HEV seropositivity associated with different occupational settings were identified using logistic regression. 47.0% (156/332) of the swine workers and 40.2% (119/296) of the poultry workers were seropositive, compared to 26.1% (35/134) in the general population. Multivariable analysis showed that human HEV infection risk increased along the pork supply chain, with the highest risk at pig slaughterhouses (adjusted OR = 3.19, 95% CI = 1.49-6.88) and pork markets (adjusted OR = 2.02, 95% CI = 1.04-3.97), but no significant higher risk was observed among poultry workers. Swine occupational exposure is associated with HEV infection, especially in workers in pig slaughterhouses and pork markets. Strengthening control measures in these settings is important for HEV control and long term HEV elimination.

18.
J Neurol ; 2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35235001

ABSTRACT

Mitochondrial disorders are a group of clinically and genetically heterogeneous multisystem disorders and peripheral neuropathy is frequently described in the context of mutations in mitochondrial-related nuclear genes. This study aimed to identify the causative mutations in mitochondrial-related nuclear genes in suspected hereditary peripheral neuropathy patients. We enrolled a large Japanese cohort of clinically suspected hereditary peripheral neuropathy patients who were mutation negative in the prescreening of the known Charcot-Marie-Tooth disease-causing genes. We performed whole-exome sequencing on 247 patients with autosomal recessive or sporadic inheritance for further analysis of 167 mitochondrial-related nuclear genes. We detected novel bi-allelic likely pathogenic/pathogenic variants in four patients, from four mitochondrial-related nuclear genes: pyruvate dehydrogenase beta-polypeptide (PDHB), mitochondrial poly(A) polymerase (MTPAP), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, beta subunit (HADHB), and succinate-CoA ligase ADP-forming beta subunit (SUCLA2). All these patients showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements. The pathological analysis of skeletal muscles revealed mild neurogenic changes without significant mitochondrial abnormalities. Targeted screening of mitochondria-related nuclear genes should be considered for patients with complex hereditary axonal polyneuropathy, accompanied by central nervous system dysfunctions, or with unexplainable multisystem disorders.

19.
Environ Int ; 162: 107157, 2022 04.
Article in English | MEDLINE | ID: mdl-35219935

ABSTRACT

Compost-based organic fertilizers made from animal manures may contain high levels of antibiotic resistance genes (ARGs). However, the factors affecting the abundance and profile of ARGs in organic fertilizers remain unclear. We conducted a national-wide survey in China to investigate the effect of material type and composting process on ARG abundance in commercial organic fertilizers and quantified the contributions of bacterial composition and mobile genetic elements (MGEs) to the structuring of ARGs, using quantitative PCR and Illumina sequencing of 16S rRNA gene amplicons. The tetracycline, sulfonamide, aminoglycoside and macrolide resistance genes were present at high levels in all organic fertilizers. Seven ARGs that confer resistance to clinically important antibiotics, including three ß-lactam resistance genes, three quinolone resistance genes and the colistin resistance gene mcr-1, were detected in 8 - 50% the compost samples, whereas the vancomycin resistance gene vanC was not detected. Raw material type had a significant (p < 0.001) effect on the ARG abundance, with composts made from animal feces except some cattle feces generally having higher loads of ARGs than those from non-animal raw materials. Composting process type showed no significant (p > 0.05) effect on ARG abundance in the organic fertilizers. MGEs exerted a greater influence on ARG composition than bacterial community, suggesting a strong mobility of ARGs in the organic fertilizers. Our study highlights the need to manage the risk of ARG dissemination from agricultural wastes.


Subject(s)
Anti-Bacterial Agents , Fertilizers , Animals , Anti-Bacterial Agents/pharmacology , Bacteria , Cattle , Drug Resistance, Bacterial/genetics , Genes, Bacterial , Macrolides , Manure/analysis , RNA, Ribosomal, 16S/genetics
20.
Inorg Chem ; 2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35200011

ABSTRACT

Herein we investigated the luminescence mechanism of one "carbene-metal-amide" copper compound with thermally activated delayed fluorescence (TADF) using density functional theory (DFT)/multireference configuration interaction, DFT, and time-dependent DFT methods with the polarizable continuum model. The experimentally observed low-energy absorption and emission peaks are assigned to the S1 state, which exhibits clear interligand and partial ligand-to-metal charge-transfer character. Moreover, it was found that a three-state (S0, S1, and T1) model is sufficient to describe the TADF mechanism, and the T2 state should play a negligible role. The calculated S1-T1 energy gap of 0.10 eV and proper spin-orbit couplings facilitate the reverse intersystem crossing (rISC) from T1 to S1. At 298 K, the rISC rate of T1 → S1 (∼106 s-1) is more than 3 orders of magnitude larger than the T1 phosphorescence rate (∼103 s-1), thereby enabling TADF. However, it disappears at 77 K because of a very slow rISC rate (∼101 s-1). The calculated TADF rate, lifetime, and quantum yield agree very well with the experimental data. Methodologically, the present work shows that only considering excited-state information at the Franck-Condon point is insufficient for certain emitting systems and including excited-state structure relaxation is important.

SELECTION OF CITATIONS
SEARCH DETAIL