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1.
PLoS Pathog ; 20(5): e1012187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718038

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.


Assuntos
Carbapenêmicos , Klebsiella pneumoniae , beta-Lactamases , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Humanos , Regulação Bacteriana da Expressão Gênica , Antibacterianos/farmacologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Pequeno RNA não Traduzido/genética , RNA Bacteriano/genética , Testes de Sensibilidade Microbiana
2.
Research (Wash D C) ; 7: 0335, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766644

RESUMO

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

3.
Adv Sci (Weinh) ; : e2306730, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704687

RESUMO

Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild-hyperthermia photothermal therapy (mild-PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)-loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild-PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)-loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness-mediated mild-PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

4.
J Colloid Interface Sci ; 669: 283-294, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38718582

RESUMO

Solar-energy-powered CO2 reduction into valuable chemical fuels represents a highly promising strategy to address the currently energy and environmental issues. Owing to the nontoxicity and robust reduction capability, lead-free Cs3Bi2Br9 perovskite quantum dots (PQDs) are regarded as an attractive material for CO2 photoreduction. Nevertheless, the potential of their applications in this field has been restricted by the severe charge recombination, resulting in unsatisfactory photocatalytic performance. Herein, a step-scheme-based Cs3Bi2Br9@Nb2O5 (CBB@Nb2O5) nanocomposite was fabricated by embedding the CBB PQDs into mesoporous Nb2O5. Experimental studies, along with theoretical calculations, revealed that the charge migration route in the CBB@Nb2O5 nanocomposite conformed to the step-scheme (S-scheme) mode, enabling effective charge separation and strong redox ability preservation. Profiting from the promoted charge separation, as well as the improved CO2 adsorption contributed by mesoporous Nb2O5, the CBB@Nb2O5 nanocomposite unveiled superior CO2 photoreduction performance, with CO evolution rate reaching 143.63 µmol g-1h-1. The present study provides a potential strategy to manufacture highly-efficient perovskite-based photocatalysts for achieving carbon neutrality.

5.
Biomed Pharmacother ; 175: 116615, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663101

RESUMO

Estrogens play a critical role in the initiation and progression of breast cancer. Estrogen receptor (ER)α, ERß, and G protein-coupled estrogen receptor are the primary receptors for estrogen in breast cancer. These receptors are mainly activated by binding with estrogens. The crosstalk between ERs and membrane growth factor receptors creates additional pathways that amplify the effects of their ligands and promote tumor growth. This crosstalk may cause endocrine therapy resistance in ERα-positive breast cancer. Furthermore, this may explain the resistance to anti-human epidermal growth factor receptor-2 (HER2) treatment in ERα-/HER2-positive breast cancer and chemotherapy resistance in triple-negative breast cancer. Accordingly, it is necessary to understand the complex crosstalk between ERs and growth factor receptors. In this review, we delineate the crosstalk between ERs and membrane growth factor receptors in breast cancer. Moreover, this review highlights the current progress in clinical treatment and discusses how pharmaceuticals target the crosstalk. Lastly, we discuss the current challenges and propose potential solutions regarding the implications of targeting crosstalk via pharmacological inhibition. Overall, the present review provides a landscape of the crosstalk between ERs and membrane growth factor receptors in breast cancer, along with valuable insights for future studies and clinical treatments using a chemotherapy-sparing regimen to improve patient quality of life.

6.
Drug Resist Updat ; 74: 101083, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593500

RESUMO

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.


Assuntos
Antibacterianos , Infecções por Klebsiella , Klebsiella pneumoniae , Filogenia , Humanos , China/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/transmissão , Infecções por Klebsiella/tratamento farmacológico , Antibacterianos/farmacologia , Polimorfismo de Nucleotídeo Único , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Epidemiologia Molecular , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Filogeografia , Sorogrupo , Genômica/métodos
7.
Small ; : e2401601, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554021

RESUMO

Photothermal catalysis, which applies solar energy to produce photogenerated e-/h+ pairs as well as provide heat input, is recognized as a promising technology for high conversion efficiency of CO2 to value-added solar fuels. In this work, a "shooting three birds with one stone" approach is demonstrated to significantly enhance the photothermal CO2 reduction over the Cs3Bi2Br9@Co3O4 (CBB@Co3O4) heterostructure. Initially, Co3O4 with photoinduced self-heating effect serves as a photothermal material to elevate the temperature of the photocatalyst, which kinetically accelerates the catalytic reaction. Meanwhile, a p-n heterojunction is constructed between the p-type Co3O4 and n-type Cs3Bi2Br9 semiconductors, which has an intrinsic built-in electric field (BEF) to facilitate the separation of photogenerated e-/h+ pairs. Furthermore, the mesoporous Co3O4 matrix can afford abundant active sites for promoting adsorption/activation of CO2 molecules. Benefiting from these synergistic effects, the as-developed CBB@Co3O4 heterostructure achieves an impressive CO2-to-CO conversion rate of 168.56 µmol g-1 h-1 with no extra heat input. This work provides an insightful guidance for the construction of effective photothermal catalysts for CO2 reduction with high solar-to-fuel conversion efficiency.

8.
Epidemiol Health ; : e2024039, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38514196

RESUMO

Objectives: To achieve the ambitious goal of eliminating schistosome infections, the Chinese government has implemented diverse control strategies. This study explored the progress of the 2 most recent national schistosomiasis control programs in an endemic area along the Yangtze River in China. Methods: We obtained village-level parasitological data from cross-sectional surveys combined with environmental data in Anhui Province, China from 1997 to 2015. A convolutional neural network (CNN) based on a hierarchical integro-difference equation (IDE) framework (i.e., CNN-IDE) was used to model spatio-temporal variations in schistosomiasis. Two traditional models were also constructed for comparison with 2 evaluation indicators: the mean-squared prediction error (MSPE) and continuous ranked probability score (CRPS). Results: The CNN-IDE model was the optimal model, with the lowest overall average MSPE of 0.04 and the CRPS of 0.19. From 1997 to 2011, the prevalence exhibited a notable trend: it increased steadily until peaking at 1.6 per 1000 in 2005, then gradually declined, stabilizing at a lower rate of approximately 0.6 per 1000 in 2006, and approaching zero by 2011. During this period, noticeable geographic disparities in schistosomiasis prevalence were observed; high-risk areas were initially dispersed, followed by contraction. Predictions for the period 2012 to 2015 demonstrated a consistent and uniform decrease. Conclusion: The proposed CNN-IDE model captured the intricate and evolving dynamics of schistosomiasis prevalence, offering a promising alternative for future risk modeling of the disease. The comprehensive strategy is expected to help diminish schistosomiasis infection, emphasizing the necessity to continue implementing this strategy.

9.
Front Cell Dev Biol ; 12: 1338448, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476263

RESUMO

Triple-negative breast cancer (TNBC) is a biologically and clinically heterogeneous disease. The G protein-coupled estrogen receptor (GPER) plays a crucial role in mediating the effect of estrogen and estrogen-like compounds in TNBC cells. Compared with other subtypes, GPER has a higher expression in TNBC. The GPER mechanisms have been thoroughly characterized and analyzed in estrogen receptor α (ERα) positive breast cancer, but not in TNBC. Our previous work revealed that a higher expression of GPER mRNA indicates a better prognosis for ERα-positive breast cancer; however, its effects in TNBC differ. Whether GPER could serve as a predictive prognostic marker or therapeutic target for TNBC remains unclear. In this review, we provide a detailed introduction to the subcellular localization of GPER, the different effects of various ligands, and the interactions between GPER and closely associated factors in TNBC. We focused on the internal molecular mechanisms specific to TNBC and thoroughly explored the role of GPER in promoting tumor development. We also discussed the interaction of GPER with specific cytokines and chemokines, and the relationship between GPER and immune evasion. Additionally, we discussed the feasibility of using GPER as a therapeutic target in the context of existing studies. This comprehensive review highlights the effects of GPER on TNBC, providing a framework and directions for future research.

10.
Sci Total Environ ; 923: 171455, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38438029

RESUMO

Neonicotinoid (NEO) insecticides have been frequently detected in natural aquatic environments. Nevertheless, the distribution of NEOs in artificial environments is not clear. The Beijing-Hangzhou Grand Canal is the longest canal in the world. The northern Jiangsu segment of the Grand Canal was selected to study the spatiotemporal variation and source of eight NEOs in the canal water and assess their ecological and health risks. The total NEO concentration in the canal water was 12-289 ng L-1 in the dry season and 18-373 ng L-1 in the wet season, which were within the concentration range in other 11 natural rivers worldwide. The average total NEO concentrations were not statistically different between the seasons; only the concentrations of imidaclothiz, thiacloprid (THI), acetamiprid, and dinotefuran were different. At city scale, the total NEO concentration in the dry season showed a decreasing trend along the water flow from Xuzhou City to Yangzhou City. The total NEO concentrations were found to be positively correlated with the sown area of farm crops and the rural labour force, indicating the agricultural influence on the spatial distribution of NEO concentrations. In the wet season, relatively high NEO concentrations were distributed in downstream sites under the influence of artificial regulation. The primary contributor to the NEO inputs into the canal was the nonpoint source in the dry and wet seasons, with a relative contribution of 68 %. THI, imidacloprid, clothianidin and thiamethoxan would produce chronic ecological risks in both seasons. Further consideration needs to be given to the above four NEOs and NEO mixtures. The human health risks that NEOs posed by drinking water were assessed based on the chronic daily intake (CDI). The maximum CDI for adults and children was lower than the reference doses. This suggested public health would not be at risk from canal water consumption.


Assuntos
Inseticidas , Tiazinas , Adulto , Criança , Humanos , Inseticidas/análise , Pequim , Neonicotinoides , Nitrocompostos , Água , Rios , China
11.
Clin Rehabil ; 38(6): 715-731, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38317586

RESUMO

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.


Assuntos
Dor Lombar , Modalidades de Fisioterapia , Humanos , Dor Lombar/reabilitação , Dor Lombar/terapia , Consenso , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Dor Aguda/terapia , Dor Aguda/reabilitação , Masculino
12.
Front Microbiol ; 15: 1320095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298894

RESUMO

Background: The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and endocarditis remains unclear. Methods: A bidirectional Mendelian randomization (MR) study was performed to detect the association between gut microbiota and endocarditis. Inverse variance weighted (IVW) method was considered the main result. Simultaneously, heterogeneity and pleiotropy tests were conducted. Results: Our study suggests that family Victivallaceae (p = 0.020), genus Eubacterium fissicatena group (p = 0.047), genus Escherichia Shigella (p = 0.024), genus Peptococcus (p = 0.028) and genus Sellimonas (p = 0.005) play protective roles in endocarditis. Two microbial taxa, including genus Blautia (p = 0.006) and genus Ruminococcus2 (p = 0.024) increase the risk of endocarditis. At the same time, endocarditis has a negative effect on genus Eubacterium fissicatena group (p = 0.048). Besides, no heterogeneity or pleiotropy was found in this study. Conclusion: Our study emphasized the certain role of specific gut microbiota in patients with endocarditis and clarified the negative effect of endocarditis on gut microbiota.

13.
Inorg Chem ; 63(8): 3702-3711, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335057

RESUMO

A long-term goal of rechargeable zinc-air batteries (ZABs) has always been to design bifunctional electrocatalysts that are robust, effective, and affordable for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). It has become a feasible method to construct metal/metal oxide interfaces to achieve superior electrocatalytic performance for ORR and OER by enhanced charge transfer. In this study, Co/Co3O4 heterojunctions were successfully prepared and encased in porous N-doped mesoporous carbon (Co/Co3O4@NC) via a simple condensation-carbonization-etching method. The extensive specific surface area of Co/Co3O4@NC facilitates effective interaction between the electrolyte and the catalyst, thereby enabling sufficient exposure of active sites for the ORR and the OER, consequently enhancing the rate of transport of active species. The well-designed Co/Co3O4@NC delivers superior ORR catalytic activity with a half-wave potential of 0.82 V (vs RHE) and a low overpotential of 347 mV at 10 mA cm-2 for OER in alkaline solution. The power density of Co/Co3O4@NC-based alkaline aqueous ZAB (156.5 mW cm-2) is superior to the commercial Pt/C + IrO2-based alkaline aqueous ZAB, and the cycling stability of ZAB is up to 220 h. In addition, Co/Co3O4@NC-based ZAB shows a high power density (50.1 mW cm-2). The construction of metal/metal oxide heterojunction encased in N-doped mesoporous carbon provides a novel route for the design of bifunctional electrocatalysts for high-performance ZABs.

14.
JMIR Public Health Surveill ; 10: e44349, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412011

RESUMO

BACKGROUND: COVID-19 screening is an effective nonpharmaceutical intervention for identifying infected individuals and interrupting viral transmission. However, questions have been raised regarding its effectiveness in controlling the spread of novel variants and its high socioeconomic costs. Therefore, the optimization of COVID-19 screening strategies has attracted great attention. OBJECTIVE: This review aims to summarize the evidence and provide a reference basis for the optimization of screening strategies for the prevention and control of COVID-19. METHODS: We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. We conducted a scoping review of the present publications on the optimization of COVID-19 screening strategies. We searched the PubMed, Web of Science, and Elsevier ScienceDirect databases for publications up to December 31, 2022. English publications related to screening and testing strategies for COVID-19 were included. A data-charting form, jointly developed by 2 reviewers, was used for data extraction according to the optimization directions of the screening strategies. RESULTS: A total of 2770 unique publications were retrieved from the database search, and 95 abstracts were retained for full-text review. There were 62 studies included in the final review. We summarized the results in 4 major aspects: the screening population (people at various risk conditions such as different regions and occupations; 12/62, 19%), the timing of screening (when the target population is tested before travel or during an outbreak; 12/62, 19%), the frequency of screening (appropriate frequencies for outbreak prevention, outbreak response, or community transmission control; 6/62, 10%), and the screening and detection procedure (the choice of individual or pooled detection and optimization of the pooling approach; 35/62, 56%). CONCLUSIONS: This review reveals gaps in the optimization of COVID-19 screening strategies and suggests that a number of factors such as prevalence, screening accuracy, effective allocation of resources, and feasibility of strategies should be carefully considered in the development of future screening strategies.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Bases de Dados Factuais , Surtos de Doenças , Viagem
15.
Biomaterials ; 306: 122497, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310827

RESUMO

High reactive oxygen species (ROS) levels provide a therapeutic opportunity to eradicate cancer stem cells (CSCs), a population of cells responsible for tumorigenesis, progression, metastasis, and recurrence. However, enhanced antioxidant systems in this population of cells attenuate ROS-inducing therapies. Here, we developed a nanoparticle-assisted combination therapy to eliminate CSCs by employing photodynamic therapy (PDT) to yield ROS while disrupting ROS defense with glutaminolysis inhibition. Specifically, we leveraged an oleic acid-hemicyanine conjugate (CyOA) as photosensitizer, a new entity molecule HYL001 as glutaminolysis inhibitor, and a biocompatible folic acid-hydroxyethyl starch conjugate (FA-HES) as amphiphilic surfactant to construct cellular and mitochondrial hierarchical targeting nanomedicine (COHF NPs). COHF NPs inhibited glutaminolysis to reduce intracellular ROS scavengers, including glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH), and to blunt oxidative phosphorylation (OXPHOS) for oxygen-conserved PDT. Compared to COLF NPs without glutaminolysis inhibitor, COHF NPs exhibited higher phototoxicity to breast cancer stem cells (BCSCs) both in vitro and in vivo. More importantly, we corroborated that marketed glutaminolysis inhibitors, such as CB839 and V9302, augment the clinically used photosensitizer (Hiporfin) for BCSCs elimination. This study develops a potent CSCs targeting strategy by combining glutaminolysis inhibition with PDT and provides significant implications for cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Terapia Combinada , Glutationa , Linhagem Celular Tumoral , Nanopartículas/química , Neoplasias/tratamento farmacológico
16.
J Virol ; 98(1): e0131923, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38084961

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses. The present study evaluated two nanobodies against PRRSV nucleocapsid (N) protein (PRRSV-N-Nb1 and -Nb2) for their anti-PRRSV activity in vitro and in vivo. The results showed that intracellularly expressed PRRSV-N-Nb1 significantly inhibited PRRSV-2 replication in MARC-145 cells (approximately 100%). Then, the PRRSV-N-Nb1 fused with porcine IgG Fc (Nb1-pFc) as a delivering tag was produced and used to determine its effect on PRRSV-2 replication in porcine alveolar macrophages (PAMs) and pigs. The inhibition rate of Nb1-pFc against PRRSV-2 in PAMs could reach >90%, and it can also inhibit viral replication in vivo. Epitope mapping showed that the motif Serine 105 (S105) in PRRSV-2 N protein was the key amino acid binding to PRRSV-N-Nb1, which is also pivotal for the self-interaction of N protein via binding to Arginine 97. Moreover, viral particles were not successfully rescued when the S105 motif was mutated to Alanine (S105A). Attachment, entry, genome replication, release, docking model analysis, and blocking enzyme-linked immunosorbent assay (ELISA) indicated that the binding of PRRSV-N-Nb1 to N protein could block its self-binding, which prevents the viral replication of PRRSV. PRRSV-N-Nb1 may be a promising drug to counter PRRSV-2 infection. We also provided some new insights into the molecular basis of PRRSV N protein self-binding and assembly of viral particles.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes serious economic losses to the swine industry worldwide, and there are no highly effective strategies for prevention. Nanobodies are considered a promising novel approach for treating diseases because of their ease of production and low costing. Here, we showed that PRRSV-N-Nb1 against PRRSV-N protein significantly inhibited PRRSV-2 replication in vitro and in vivo. Furthermore, we demonstrated that the motif Serine 105 (S105) in PRRSV-N protein was the key amino acid to interact with PRRSV-N-Nb1 and bond to its motif R97, which is important for the self-binding of N protein. The PRRSV-N-Nb1 could block the self-interaction of N protein following viral assembly. These findings not only provide insights into the molecular basis of PRRSV N protein self-binding as a key factor for viral replication for the first time but also highlight a novel target for the development of anti-PRRSV replication drugs.


Assuntos
Proteínas do Nucleocapsídeo , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Anticorpos de Domínio Único , Animais , Aminoácidos , Linhagem Celular , Proteínas do Nucleocapsídeo/metabolismo , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Serina , Anticorpos de Domínio Único/farmacologia , Suínos , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
17.
Small ; 20(2): e2305566, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37661354

RESUMO

Regulating the built-in electric field (BEF) in the heterojunction is is a great challenge in developing high-efficiency photocatalysts. Herein, by tailoring the content of oxygen vacancies in the constituent reduction semiconductor (mesoporous CeO2-x ), a precise Fermi level (EF ) regulation of CeO2-x is realized, yielding an amplified EF gap and intensified BEF in the Cs3 Bi2 Br9 perovskite quantum dots/CeO2-x S-scheme heterojunction. Such an enhanced BEF offers a strong driving force for directional electron transfer, boosting charge separation in the S-scheme heterojunction. As a result, the optimized Cs3 Bi2 Br9 /CeO2-x heterojunction delivers a remarkable CO2 conversion efficiency, with an impressive CO production rate of 80.26 µmol g-1  h-1 and a high selectivity of 97.6%. The S-scheme charge transfer mode is corroborated comprehensively by density functional theory (DFT) calculations, in situ X-ray photoelectron spectroscopy (XPS), and photo-irradiated Kelvin probe force microscopy (KPFM). Moreover, diffuse reflectance infrared Fourier transform spectra (DRIFTS) and theoretical calculations are conducted cooperatively to reveal the CO2 photoreduction pathway.

18.
Death Stud ; 48(4): 417-426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37416944

RESUMO

Death attitudes can have significant impacts on individuals' mental health. The present study used a person-centered approach to identify 588 Chinese college students' profiles of death attitudes (i.e., fear of death, death avoidance, neutral acceptance, escape acceptance, and approach acceptance), as well as their associations with socio-demographic factors and mental health outcomes. Latent profile analysis identified five subgroups of students: healthy (28.8%), acceptant (11.7%), indifferent (43.5%), paradoxical (10.7%), and avoidant (5.3%). The healthy profile had the most favorable mental health outcomes, whereas the paradoxical profile had the least favorable mental health outcomes. Moreover, women and students from better-resourced universities were more likely to report adaptive patterns of death attitudes. Our findings demonstrated the advantages of using a person-centered approach to achieve a more nuanced understanding of Chinese college students' death attitudes in relation to their mental health. The findings can inform death-related education and mental health interventions for college students.


Assuntos
Medo , Saúde Mental , Humanos , Feminino , Estudantes/psicologia , Universidades
19.
Int J Psychophysiol ; 195: 112265, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37981033

RESUMO

Multitasking with two or more media and devices has become increasingly common in our daily lives. The impact of chronic media multitasking on our cognitive abilities has received extensive concern. Converging studies have shown that heavy media multitaskers (HMM) have a greater demand for sensation seeking and are more easily distracted by task-irrelevant information than light media multitaskers (LMM). In this study, we analyzed the electroencephalogram data recorded during resting-state periods to investigate whether HMM and LMM differ with regard to basic resting network activation. Microstate analysis revealed that the activation of the attention network is weakened while the activation of the salience network is enhanced in HMM compared to LMM. This suggests that HMM's attention control is more likely to be guided by surrounding stimuli, which indirectly supports the deficit-producing hypothesis. Moreover, our results revealed that HMM had an enhanced visual network and may feel less comfortable than LMM during resting-state periods with eyes closed, supporting the view that HMM require more sensation seeking than LMM. Taken together, these results indicate that chronic media multitasking leads to HMM allocating attention in a bottom-up or stimulus-driven manner, while LMM deploy a top-down approach.


Assuntos
Cognição , Emoções , Humanos , Cognição/fisiologia , Eletroencefalografia , Olho , Encéfalo
20.
Nanomaterials (Basel) ; 13(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38063721

RESUMO

The understanding of amorphous and heterojunction materials has been widely used in the field of electromagnetic wave absorption due to their unique physical and chemical properties. However, the effectiveness of individual strategies currently used is still limited. Well-designed compositions and amorphous structures simplify the effect of different polarization mechanisms on the absorption of electromagnetic waves. In this work, through the carbonization and controlled phosphating of one-dimensional Co Metal-Organic Framework (Co-MOF) nanorods, the synthesis of complex components and amorphous CoPx with phosphorus vacancies is successfully accomplished, thus adjusting the optimization of electromagnetic parameters. Phosphorus-vacancy-induced defective polarization loss and enhanced-electronegativity-differences-induced dipole polarization loss synergistically as a dual-polarization strategy significantly improved the electromagnetic parameters and impedance matching. In conclusion, the electromagnetic parameters of the Co@CoPx@C composites are indeed significantly regulated, with reflection losses of -55 dB and a bandwidth of up to 5.5 GHz. These innovative research ideas provide instructive thinking for the development of amorphous absorbers with vacancies.

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