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1.
J Adv Res ; 39: 147-156, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35777904

RESUMO

INTRODUCTION: Face masks are regarded as effective Personal Protective Equipment (PPE) during the COVID-19 pandemic. However, the dominant polypropylene (PP)-based masks are devoid of antiviral/antibacterial activities and create enormous environmental burdens after disposal. OBJECTIVES: Here we report a facile and potentially scalable method to fabricate biodegradable, breathable, and biocidal cellulose nonwovens (BCNWs) to address both environmental and hygienic problems of commercially available face masks. METHODS: TEMPO-oxidized cellulose nonwovens are rendered antiviral/antibacterial via covalent bonding with disinfecting polyhexamethylene guanidine or neomycin sulfate through carbodiimide coupling chemistry. RESULTS: The obtained results showed that the BCNWs have virucidal rate of >99.14%, bactericidal efficiency of >99.51%, no leaching-out effect, and excellent air permeability of >1111.5 mm s-1. More importantly, the as-prepared BCNWs can inactivate SARS-CoV-2 instantly. CONCLUSIONS: This strategy provides a new platform for the green fabrication of multifunctional cellulose nonwovens as scalable bio-protective layers with superior performance for various PPE in fighting COVID-19 or future pandemics. Additionally, replacing the non-biodegradable non-antimicrobial PP-based masks with the cellulose-based masks can reduce the plastic wastes and lower the greenhouse gas production from the incineration of disposed masks.


Assuntos
COVID-19 , Equipamento de Proteção Individual , Antibacterianos/farmacologia , Antivirais , COVID-19/prevenção & controle , Celulose , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
2.
Food Chem ; 395: 133641, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-35816986

RESUMO

In this study, we reported for the first time that the natural protein/polysaccharide hybrid nanoparticles (PPH NPs) with a diameter of âˆ¼ 129 nm, originating from Lactobacillus plantarum fermented cheese whey, could act as green-based NPs for stabilizing Pickering emulsions. Characterizations of PPH NPs showed that the negative-charged PPH NPs were composed of âˆ¼ 37.7% total protein and âˆ¼ 7.3% polysaccharide bearing several functional groups, such as -OH, -NH, -COOH, etc.; and displayed excellent emulsifying capacity in preparing oil-in-water Pickering emulsions. The obtained emulsions exhibited gel-like behavior with excellent stability against the variation of pH, ionic strength, and temperature. Confocal observations showed that PPH NPs effectively adsorbed and anchored at the oil-water interface, thus creating the steric hindrance to inhibit droplet coalescence. This research is of importance in developing novel and biocompatible Pickering stabilizers with outstanding performance, as well as enable a versatile design of stable Pickering emulsions suitable for food industries.


Assuntos
Nanopartículas , Água , Emulsões/química , Nanopartículas/química , Tamanho da Partícula , Polissacarídeos , Água/química
3.
J Asian Nat Prod Res ; : 1-10, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35763370

RESUMO

Erysolin and its two metabolites which were found in blood, ERY-GSH and ERY-NAC, were synthesized by alkylation, amination, isothiocyanation and oxidation reactions from 1-bromo-4-chlorobutane and sodium methyl mercaptide. The reaction temperature, time, feed ratios and purification method were also optimized. The synthesis method was simple, green, safe and low-cost. Erysolin, ERY-GSH and ERY-NAC showed good antitumor activities against MCF-7, HeLa, HepG2, A549 and SW480 cells, which suggested that the antitumor mechanism of erysolin can also be clarified from its metabolites in addition to itself.

4.
Small ; 18(27): e2201300, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35678523

RESUMO

The treatment of diabetic wounds remains challenging due to the excess levels of oxidative stress, vulnerability to bacterial infection, and persistent inflammation response during healing. The development of hydrogel wound dressings with ideal anti-inflammation, antioxidant, and anti-infective properties is an urgent clinical requirement. In the present study, an injectable thermosensitive niobium carbide (Nb2 C)-based hydrogel (Nb2 C@Gel) with antioxidative and antimicrobial activity is developed to promote diabetic wound healing. The Nb2 C@Gel system is composed of Nb2 C and a PLGA-PEG-PLGA triblock copolymer. The fabricated Nb2 C nanosheets (NSs) show good biocompatibility during in vitro cytotoxicity and hemocompatibility assays and in vivo toxicity assays. In vitro experiments show that Nb2 C NSs can efficiently eliminate reactive oxygen species (ROS), thus protecting cells in the wound from oxidative stress damage. Meanwhile, Nb2 C NSs also exhibit good near-infrared (NIR) photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli. In vivo results demonstrate that Nb2 C@Gel promotes wound healing by attenuating ROS levels, reducing oxidative damage, eradicating bacterial infection under NIR irradiation, and accelerating angiogenesis. To summarize, the Nb2 C@Gel system, with its ROS-scavenging, photothermal antimicrobial and hemostatic activities, can be a promising and effective strategy for the treatment of diabetic wounds.


Assuntos
Infecções Bacterianas , Diabetes Mellitus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes , Escherichia coli , Humanos , Hidrogéis , Nióbio , Espécies Reativas de Oxigênio , Cicatrização
5.
Innovation (Camb) ; 3(4): 100259, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35647572

RESUMO

Effective screening modalities are currently available for only a small subset of cancers, and they generally have suboptimal performance with complicated procedures. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for early detection of cancers. Genetic and epigenetic alterations in plasma circulating cell-free DNA (cfDNA) have shown the potential to revolutionize methods of early detection of cancers and facilitate subsequent diagnosis to improve survival of patients. The medical interest in cfDNA assays has been inspired by emerging single- and multi-early detection of cancers studies. This review summarizes current technological and clinical advances, in the hopes of providing insights into the development and applications of cfDNA assays in various cancers and clinical scenarios. The key phases of clinical development of biomarkers are highlighted, and the future developments of cfDNA-based liquid biopsies in early detection of cancers are outlined. It is hoped that this study can boost the potential integration of cfDNA-based early detection of cancers into the current clinical workflow.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35682055

RESUMO

Groundwater contamination by potentially harmful elements (PHEs) originating from the weathering of granitic and gneissic rock dissolution poses a public health concern worldwide. This study investigated physicochemical variables and PHEs in the groundwater system and mine water of the Adenzai flood plain region, in Pakistan, emphasizing the fate distribution, source provenance, chemical speciation, and health hazard using the human health risk assessment HHRA-model. The average concentrations of the PHEs, viz., Ni, Mn, Cr, Cu, Cd, Pb, Co, Fe, and Zn 0.23, were 0.27, 0.07, 0.30, 0.07, 0.06, 0.08, 0.68, and 0.23 mg/L, respectively. The average values of chemical species in the groundwater system, viz., H+, OH-, Ni2+, Mn2+, Mn3+, Cr3+, Cr6+, Cu+, Cu2+, Cd2+, Pb2+, Pb4+, Co2+, Co3+, Fe2+, Fe3+, and Zn2+, were 1.0 × 10-4 ± 1.0 × 10-6, 1.0 × 10-4 ± 9.0 × 10-7, 2.0 × 10-1 ± 1.0 × 10-3, 3.0 × 10-1 ± 1.0 × 10-3, 1.0 × 10-22 ± 1.0 × 10-23, 4.0 × 10-6 ± 2.0 × 10-6, 4.0 × 10-11 ± 2.0 × 10-11, 9.0 × 10-3 ± 1.0 × 10-2, 2.0 × 10-1 ± 2.0 × 10-3, 7.0 × 10-2 ± 6.0 × 10-2, 5.0 × 10-2 ± 5.0 × 10-2, 2.0 × 10-2 ± 1.5 × 10-2, 6.0 × 10-2 ± 4.0 × 10-2, 8.0 × 10-31 ± 6.0 × 10-31, 3.0 × 10-1 ± 2.0 × 10-4, 4.0 × 10-10 ± 3.0 × 10-10, and 2.0 × 10-1 ± 1.0 × 10-1. The mineral compositions of PHEs, viz. Ni, were bunsenite, Ni(OH)2, and trevorite; Mn viz., birnessite, bixbyite, hausmannite, manganite, manganosite, pyrolusite, and todorokite; Cr viz., chromite and eskolaite; Cu viz., CuCr2O4, cuprite, delafossite, ferrite-Cu, and tenorite; Cd viz., monteponite; Pb viz, crocoite, litharge, massicot, minium, plattnerite, Co viz., spinel-Co; Fe viz., goethite, hematite, magnetite, wustite, and ferrite-Zn; and Zn viz., zincite, and ZnCr2O4 demarcated undersaturation and supersaturation. However, EC, Ca2+, K+, Na+, HCO3-, Cr, Cd, Pb, Co, and Fe had exceeded the WHO guideline. The Nemerow's pollution index (NPI) showed that EC, Ca2+, K+, Na+, HCO3-, Mn, Cd, Pb, Co, and Fe had worse water quality. Principal component analysis multilinear regression (PCAMLR) and cluster analysis (CA) revealed that 75% of the groundwater contamination originated from geogenic inputs and 18% mixed geogenic-anthropogenic and 7% anthropogenic sources. The HHRA-model suggested potential non-carcinogenic risks, except for Fe, and substantial carcinogenic risks for evaluated PHEs. The women and infants are extremely exposed to PHEs hazards. The non-carcinogenic and carcinogenic risks in children, males, and females had exceeded their desired level. The HHRA values of PHEs exhibited the following increasing pattern: Co > Cu > Mn > Zn > Fe, and Cd > Pb > Ni > Cr. The higher THI values of PHEs in children and adults suggested that the groundwater consumption in the entire region is unfit for drinking, domestic, and agricultural purposes. Thus, all groundwater sources need immediate remedial measures to secure health safety and public health concerns.


Assuntos
Água Subterrânea , Metais Pesados , Adulto , Cádmio/análise , Criança , Monitoramento Ambiental , Feminino , Humanos , Chumbo/análise , Metais Pesados/análise , Saúde Pública , Medição de Risco , Qualidade da Água
7.
Environ Sci Technol ; 56(14): 10172-10182, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35770491

RESUMO

Ambient PM2.5 (fine particulate matter with aerodynamic diameters ≤ 2.5 µm) is thought to be associated with the development of diabetes, but few studies traced the effects of PM2.5 components and pollution sources on the change in the fasting blood glucose (FBG). In the present study, we assessed the associations of PM2.5 constituents and their sources with the FBG in a general Chinese population aged over 40 years. Exposure to PM2.5 was positively associated with the FBG level, and each interquartile range (IQR) increase in a lag period of 30 days (18.4 µg/m3) showed the strongest association with an elevated FBG of 0.16 mmol/L (95% confidence interval: 0.04, 0.28). Among various constituents, increases in exposed elemental carbon, organic matter, arsenic, and heavy metals such as silver, cadmium, lead, and zinc were associated with higher FBG, whereas barium and chromium were associated with lower FBG levels. The elevated FBG level was closely associated with the PM2.5 from coal combustion, industrial sources, and vehicle emissions, while the association with secondary sources was statistically insignificant. Improving air quality by tracing back to the pollution sources would help to develop well-directed policies to protect human health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Glicemia , China , Carvão Mineral , Estudos Transversais , Poeira , Exposição Ambiental/análise , Jejum , Humanos , Minerais , Material Particulado/análise
8.
Artigo em Inglês | MEDLINE | ID: mdl-35661301

RESUMO

Globally, potentially toxic elements (PTEs) and bacterial contamination pose health hazards, persistency, and genotoxicity in the groundwater aquifer. This study evaluates PTE concentration, carcinogenic and noncarcinogenic health hazards, groundwater quality indexing (GWQI-model), source provenance, and fate distribution in the groundwater of Hindukush ranges, Pakistan. The new estimates of USEPA equations record new research dimensions for carcinogenic and noncarcinogenic hazards. The principal component analysis (PCA), mineral phases, and spatial distribution determine groundwater contamination and its impacts. The average concentrations of PTEs, viz., Cd, Cu, Co, Fe, Pb, and Zn, were 0.06, 0.27, 0.07, 0.55, 0.05, and 0.19 mg/L, and E. coli, F. coli, and P. coli were 27.5, 24.0, and 19.0 CFU/100 ml. Moreover, the average values of basic minerals, viz., anhydrite, aragonite, calcite, dolomite, gypsum, halite, and hydroxyl apatite, were 0.4, 2.4, 2.6, 5.1, 0.6, and - 4.0, 11.2, and PTE minerals like monteponite, tenorite, cuprite, cuprous ferrite, cupric ferrite, ferrihydrite, goethite, hematite, lepidocrocite, maghemite, magnetite, massicot, minium, litharge, plattnerite, and zincite were - 5.5, 2.23, 4.65, 18.56, 20.0, 4.84, 7.54, 17.46, 6.66, 9.67, 22.72, - 3.36, 22.9, 3.16, - 18.0, and 1.46. The groundwater showed carcinogenic and non-carcinogenic health hazards for children and adults. The GWQI-model showed that 58.3% of samples revealed worse water quality. PCA revealed rock weathering, mineral dissolution, water-rock interaction, and industrial effluents as the dominant factors influencing groundwater chemistry. Carbonate weathering and ion exchange play vital roles in altering CaHCO3 type to NaHCO3 water. In this study, E. coli, F. coli, P. coli, EC, turbidity, TSS, PO43─, Na+, Mg+2, Ca+2, Cd, Co, Fe, and Pb have exceeded the World Health Organization (WHO) guidelines. The carcinogenic and non-carcinogenic impacts of PTEs and bacterial contamination declared that the groundwater is unfit for drinking and domestic purposes.

9.
Microb Cell Fact ; 21(1): 90, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35590356

RESUMO

BACKGROUND: A total of 11 ß-glucosidases are predicted in the genome of Trichoderma reesei, which are of great importance for regulating cellulase biosynthesis. Nevertheless, the relevant function and regulation mechanism of each ß-glucosidase remained unknown. RESULTS: We evidenced that overexpression of cel1b dramatically decreased cellulase synthesis in T. reesei RUT-C30 both at the protein level and the mRNA level. In contrast, the deletion of cel1b did not noticeably affect cellulase production. Protein CEL1B was identified to be intracellular, being located in vacuole and cell membrane. The overexpression of cel1b reduced the intracellular pNPGase activity and intracellular/extracellular glucose concentration without inducing carbon catabolite repression. On the other hand, RNA-sequencing analysis showed the transmembrane transport process and endoplasmic reticulum function were affected noticeably by overexpressing cel1b. In particular, some important sugar transporters were notably downregulated, leading to a compromised cellular uptake of sugars including glucose and cellobiose. CONCLUSIONS: Our data suggests that the cellulase inhibition by cel1b overexpression was not due to the ß-glucosidase activity, but probably the dysfunction of the cellular transport process (particularly sugar transport) and endoplasmic reticulum (ER). These findings advance the knowledge of regulation mechanism of cellulase synthesis in filamentous fungi, which is the basis for rationally engineering T. reesei strains to improve cellulase production in industry.


Assuntos
Celulase , Trichoderma , Celobiose/metabolismo , Celulase/metabolismo , Retículo Endoplasmático/metabolismo , Glucose/metabolismo , Hypocreales , Trichoderma/genética , Trichoderma/metabolismo , beta-Glucosidase/genética , beta-Glucosidase/metabolismo
10.
J Cell Mol Med ; 26(11): 3213-3222, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35582950

RESUMO

Oral-facial-digital syndrome (OFDS) is a multisystemic ciliopathic disorder with an autosomal recessive mode of inheritance. OFDS usually manifests with typical craniofacial anomalies and variable occurrence of polydactyly. Germline variants in CPLANE1 cause OFDS VI. In this study, we investigated a 26-year-old Chinese female patient who was 23+1  weeks pregnant. She had a history of adverse pregnancy outcomes with multiple foetal malformations. We performed ultrasonography and identified the foetus as having a posterior fossa Blake cyst and postaxial polydactyly. The patient decided to terminate her pregnancy, and further genetic molecular analysis was performed. We identified the aborted foetus as having postaxial polydactyly. Whole-exome sequencing identified a missense variant (c.3599C>T, p.A1200V) in exon 20 and a c.834+1G>T variant in exon 7 of CPLANE1 (NM_023073.3) in the foetus. Sanger sequencing confirmed that these variants came from the parents of the foetus. In this study, we investigated a family with OFDS VI through genetic testing and bioinformatics analysis, which provided powerful help for prenatal diagnosis. Then, we demonstrated that the cell migration rate and the number of cilia were decreased after interference with CPLANE1 expression in NIH/3T3 cells. After CPLANE1 knockdown, the Hh signalling pathway was inhibited, and the Hh pathway activator SAG reversed the inhibitory effect. This is the first report of a family with OFDS VI in the Chinese population.


Assuntos
Anormalidades Múltiplas , Síndromes Orofaciodigitais , Polidactilia , Anormalidades Múltiplas/genética , Adulto , Animais , Cílios/genética , Feminino , Dedos/anormalidades , Humanos , Camundongos , Síndromes Orofaciodigitais/diagnóstico , Síndromes Orofaciodigitais/genética , Gravidez , Dedos do Pé/anormalidades , Sequenciamento Completo do Exoma
11.
Sci Total Environ ; 838(Pt 1): 155991, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35588806

RESUMO

Groundwater arsenic pollution has received much attention worldwide for decades as a serious threat to public health, but the mechanisms responsible for arsenic mobilization are not fully understood. Groundwater and bore drilling sediment samples from Qiji county, a small geographical agricultural area with endemic arsenicosis, are collected for demonstrating the occurrence and speciation of arsenic in groundwater and sediments, and arsenic release between solid-liquid phase influenced by human activities. Results show that arsenic concentrations in groundwater vary from 5 µg/L to 19.6 µg/L, with 80% exceeding the maximum permissible limits required by WHO (10 µg/L) for drinking water and therefore constituting a health risk for humans. In a weak oxidizing environment (oxidation-reduction potential (ORP): 12.9 mV-151 mV), inorganic As(V) accounts for 85% of total dissolved As, which to some extent alleviates the harm of As pollution on humans. Total As content in the sediments is in the range of 6.98 mg/kg and 14.34 mg/kg (median of 10.71 mg/kg), three times higher than the average value of many countries. Sequential chemical leaching indicates that 11% of arsenic in sediments is labile bound and may be closely related to the arsenic in groundwater. Additionally, irrigation intensity contributes to arsenic release with diverse As3+/As5+ by dissolving weakly bound arsenic rapidly. Subsequently part of As(III) is oxidized to As(V). Competitive and/or alkaline desorption of As(V), which had been adsorbed by FeMn (hydrous)-oxides and carbonates in the unsaturated zone and the aquifer, exerts a significant role in releasing arsenic into the groundwater. Our study indicates that systematic management and regulation of irrigation intensity are required to prevent further deterioration of groundwater resources.


Assuntos
Arsênio , Água Subterrânea , Poluentes Químicos da Água , Arsênio/análise , Carbonatos , Monitoramento Ambiental , Sedimentos Geológicos/química , Água Subterrânea/química , Humanos , Poluentes Químicos da Água/análise
12.
Sci Rep ; 12(1): 6840, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477983

RESUMO

Cadmium (Cd), though potentially beneficial at lower levels to some plant species, at higher levels is a toxic metal that is detrimental to plant growth and development. Cd is also a carcinogen to humans and other contaminated plant consumers, affecting the kidneys and reducing bone strength. In this study we investigated responses of growth, chlorophyll content, reactive oxygen species levels, and antioxidant responses to Cd in honeysuckle leaves (Lonicera japonica Thunb.), a potential Cd hyperaccumulator. Results indicated that plant height, dry weight, leaf area, and chlorophyll content increased when honeysuckle was exposed to 10 mg kg-1 or 30 mg kg-1 Cd (low concentration). However, in response to 150 mg kg-1 or 200 mg kg-1 Cd (high concentration) these growth parameters and chlorophyll content significantly decreased relative to untreated control plant groups. Higher levels of superoxide radical (O2·-) and hydrogen peroxide (H2O2) were observed in high concentration Cd groups. The activities of ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase were enhanced with exposure to increasing levels of Cd. Additionally, the Ascorbate-Glutathione (AsA-GSH) cycle was activated for the removal of H2O2 in honeysuckle in response to elevated Cd. The Pearson correlation analysis, a redundancy analysis, and a permutation test indicated that proline and APX were dominant antioxidants for removing O2·- and H2O2. The antioxidants GSH and non-protein thiols (NPTs) also increased as the concentration of Cd increased.


Assuntos
Antioxidantes , Lonicera , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Cádmio/toxicidade , Clorofila , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio , Lonicera/metabolismo , Estresse Oxidativo , Compostos Fitoquímicos
13.
J Agric Food Chem ; 70(16): 4881-4888, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35416662

RESUMO

Fluoxapiprolin is a new oxysterol binding protein inhibitor (OSBPI), which showed excellent inhibitory activity to plant pathogenic oomycetes. Its resistance risk and mechanism in Phytophthora infestans are unclear. In the current study, the sensitivities of 103 P. infestans isolates to fluoxapiprolin were investigated, and a unimodal distribution with a mean EC50 value of 0.00035 µg/mL was observed. Four types of resistant mutants, with a resistance factor from 14 to more than 1000, and point mutations S768I+N837I, S768I+L860I, S768I, and I877F in PiORP1, were acquired using fungicide adaption. The fitness of the mutants was similar to or lower than that of the corresponding parental isolate. Positive cross-resistance was detected between fluoxapiprolin and oxathiapiprolin. The point mutations were verified in P. sojae homologue positions using the CRISPR/Cas9 genome editing system. Transformants containing S768I+N837I or S768I+L860I, showed high fluoxapiprolin resistance (RF > 1000). In conclusion, the risk of P. infestans resistance to fluoxapiprolin is moderate, and novel point mutation types S768I+N837I or S768I+L860I could cause high fluoxapiprolin resistance in P. infestans.


Assuntos
Fungicidas Industriais , Phytophthora infestans , Fungicidas Industriais/farmacologia , Edição de Genes , Doenças das Plantas , Mutação Puntual
14.
Eur J Nutr ; 61(5): 2775-2797, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35290477

RESUMO

PURPOSE: A possible link between pescadillo 1 (PES1) and lipid metabolism has been reported. However, whether PES1 is involved in the effects of daily caloric restriction (CR) and alternate-day fasting (ADF) interventions on diabetes-related lipid dysregulation is not elucidated. The current study aims are to explore the role of PES1 in effects of CR and ADF on diabetic mice and related mechanism. METHODS: Eight-week-old male db/db mice with type 2 diabetes mellitus (T2DM) were randomly divided into untreated T2DM, CR and ADF groups. McArdle hepatocytes were treated with 48 h high glucose (HG), 48 h normal glucose (NG) and 24 h HG plus 24 h NG, respectively. Pes1 siRNA and overexpression plasmid were, respectively, transfected into liver cells, and AAV9-Pes1-shRNA was injected into db/db mice. RESULTS: After 12-week interventions, the peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1A (CPT1A) levels in livers of T2DM mice were enhanced by CR and ADF interventions with reductions of hepatic and plasma triglycerides. Unexpectedly, hepatic PES1 levels were downregulated by two interventions, consistent with the results of 48 h NG and 24 h HG plus 24 h NG-treated cells. Moreover, CPT1A level was upregulated in Pes1-siRNA-treated cells and AAV9-Pes1-shRNA injected murine livers, in contrast to Pes1 overexpression in cultured cells. Mechanistically, 48 h NG or 24 h HG plus 24 h NG treatment increased PPAR-α binding to Pes1 promoter, suppressing the PES1 expression, thereby lowering the PES1-mediated ubiquitination of CPT1A. CONCLUSION: The present study suggests that CR and ADF may improve lipid dysregulation in diabetic mice by downregulating hepatic PES1.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Restrição Calórica , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Jejum/fisiologia , Glucose/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Interferente Pequeno/metabolismo , Triglicerídeos/metabolismo
15.
ACS Appl Mater Interfaces ; 14(12): 14059-14071, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35298140

RESUMO

Diabetic foot ulcer is a serious complication in diabetes patients, imposing a serious physical and economic burden to patients and to the healthcare system as a whole. Oxidative stress is thought to be a key driver of the pathogenesis of such ulcers. However, no antioxidant drugs have received clinical approval to date, underscoring the need for the further development of such medications. Hydrogels can be applied directly to the wound site, wherein they function to prevent infection and maintain local moisture concentrations, in addition to serving as a reservoir for the delivery of a range of therapeutic compounds with the potential to expedite wound healing in a synergistic manner. Herein, we synthesized Prussian blue nanoparticles (PBNPs) capable of efficiently scavenging reactive oxygen species (ROS) owing to their ability to mimic the activity of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD). In the context of in vitro oxidative stress, these PBNPs were able to protect against cytotoxicity, protect mitochondria from oxidative stress-related damage, and restore nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activity. To expand on these results in an in vivo context, we prepared a thermosensitive poly (d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA) hydrogel (PLEL)-based wound dressing in which PBNPs had been homogenously incorporated, and we then used this dressing as a platform for controlled PBNP release. The resultant PBNPs@PLEL wound dressing was able to improve diabetic wound healing, decrease ROS production, promote angiogenesis, and reduce pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels within diabetic wounds. Overall, our results suggest that this PBNPs@PLEL platform holds great promise as a treatment for diabetic foot ulcers.


Assuntos
Diabetes Mellitus , Pé Diabético , Nanopartículas , Ferrocianetos , Humanos , Hidrogéis/farmacologia , Mitocôndrias , Espécies Reativas de Oxigênio , Cicatrização
16.
Environ Entomol ; 51(2): 521-527, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35244159

RESUMO

The community structure and diversity of hymenopteran parasitoids of the agromyzid leafminer Chromatomyia horticola (Diptera: Agromyzidae) were studied in agricultural, urban, and natural habitats in Changchun, Northeast China. In agricultural habitats, a total of 3,380 individuals and 19 species were collected, and the dominant species were Diglyphus isaea (Walker) (Hymenoptera: Eulophidae) (71.15%) and Chrysocharis pentheus (Walker) (Hymenoptera: Eulophidae) (12.10%). In urban habitats, a total of 5,996 individuals and 21 species were collected. There were three dominant species, C. pentheus (26.68%), Chrysocharis phryne (Walker) (Hymenoptera: Eulophidae) (22.18%), and D. isaea (22.13%). In natural habitats, a total of 1,566 individuals and 26 species were collected. There were three dominant species, C. pentheus (30.52%), D. isaea (15.52%), and Pediobius metallicus (Nees) (Hymenoptera: Eulophidae) (12.26%). The diversity indices of the parasitoid community in urban and natural habitats were higher than that in agricultural habitats, and the richness index in natural habitats was higher than that in agricultural and urban habitats. These results suggest that there are differences in the community composition and dynamics of parasitoids in different habitats. Hymenopteran parasitoids of C. horticola are less abundant in natural habitats; however, species richness is greater, and can be used as a species reserve for biological control.


Assuntos
Dípteros , Himenópteros , Agricultura , Animais , China , Ecossistema
17.
BMC Med ; 20(1): 64, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130881

RESUMO

BACKGROUND: DNA methylation-associated studies on biliary tract cancer (BTC), including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), may improve the BTC classification scheme. We proposed to identify the shared methylation changes of BTCs and investigate their associations with genomic aberrations, immune characteristics, and survival outcomes. METHODS: Multi-dimensional data concerning mutation, DNA methylation, immune-related features, and clinical data of 57 CCAs and 48 GBCs from Eastern Hepatobiliary Surgery Hospital (EHSH) and 36 CCAs in the TCGA-CHOL cohort were analyzed. RESULTS: In our cohort including 24 intrahepatic CCAs (iCCAs), 20 perihilar CCAs (pCCAs), 13 distal CCAs (dCCAs), and 48 GBCs, 3369 common differentially methylated regions (DMRs) were identified by comparing tumor and non-tumor samples. A lower level of methylation changes of these common DMRs was associated with fewer copy number variations, fewer mutational burden, and remarkably longer overall survival (OS, hazard ratio [HR] = 0.07, 95% confidence interval [CI] 0.01-0.65, P = 0.017). Additionally, a 12-marker model was developed and validated for prognostication after curative surgery (HR = 0.21, 95% CI 0.10-0.43, P < 0.001), which exhibited undifferentiated prognostic effects in subgroups defined by anatomic location (iCCAs, d/pCCAs, GBCs), TNM stage, and tumor purity. Its prognostic utility remained significant in multivariable analysis (HR = 0.26, 95% CI 0.11-0.59, P = 0.001). Moreover, the BTCs with minimal methylation changes exhibited higher immune-related signatures, infiltration of CD8+ lymphocytes, and programmed death-ligand 1 (PD-L1) expression, indicating an inflamed tumor immune microenvironment (TIME) with PD-L1 expression elicited by immune attack, potentially suggesting better immunotherapy efficacy. CONCLUSIONS: In BTCs, DNA methylation is a powerful tool for molecular classification, serving as a robust indicator of genomic aberrations, survival outcomes, and tumor immune microenvironment. Our integrative analysis provides insights into the prognostication after curative surgery and patient selection for immunotherapy.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , Variações do Número de Cópias de DNA , Metilação de DNA/genética , Humanos , Microambiente Tumoral
18.
Genes (Basel) ; 13(2)2022 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-35205425

RESUMO

Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a major challenge in genetic test interpretation and disease diagnosis. Understanding the phenotypic consequences of VUSs can provide clinical guidance regarding LGMD risk and therapy. In this review, we provide a brief overview of the subtypes of LGMD, disease diagnosis, current classification systems for investigating VUSs, and a potential deep mutational scanning approach to classify VUSs in LGMD-related genes.


Assuntos
Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Mutação
19.
Comput Struct Biotechnol J ; 20: 824-837, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126885

RESUMO

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has challenged public health around the world. Currently, there is an urgent need to explore antiviral therapeutic targets and effective clinical drugs. In this study, we systematically summarized two main therapeutic strategies against COVID-19, namely drugs targeting the SARS-CoV-2 life cycle and SARS-CoV-2-induced inflammation in host cells. The development of above two strategies is implemented by repurposing drugs and exploring potential targets. A comprehensive summary of promising drugs, especially cytokine inhibitors, and traditional Chinese medicine (TCM), provides recommendations for clinicians as evidence-based medicine in the actual clinical COVID-19 treatment. Considering the emerging SARS-CoV-2 variants greatly impact the effectiveness of drugs and vaccines, we reviewed the appearance and details of SARS-CoV-2 variants for further perspectives in drug design, which brings updating clues to develop therapeutical agents against the variants. Based on this, the development of broadly antiviral drugs, combined with immunomodulatory, or holistic therapy in the host, is prior to being considered for therapeutic interventions on mutant strains of SARS-CoV-2. Therefore, it is highly acclaimed the requirements of the concerted efforts from multi-disciplinary basic studies and clinical trials, which improves the accurate treatment of COVID-19 and optimizes the contingency measures to emerging SARS-CoV-2 variants.

20.
Psychometrika ; 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35089496

RESUMO

Estimation of the large Q-matrix in cognitive diagnosis models (CDMs) with many items and latent attributes from observational data has been a huge challenge due to its high computational cost. Borrowing ideas from deep learning literature, we propose to learn the large Q-matrix by restricted Boltzmann machines (RBMs) to overcome the computational difficulties. In this paper, key relationships between RBMs and CDMs are identified. Consistent and robust learning of the Q-matrix in various CDMs is shown to be valid under certain conditions. Our simulation studies under different CDM settings show that RBMs not only outperform the existing methods in terms of learning speed, but also maintain good recovery accuracy of the Q-matrix. In the end, we illustrate the applicability and effectiveness of our method through a TIMSS mathematics data set.

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