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1.
Nature ; 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019149

RESUMO

SARS-CoV-2, the causative agent of COVID-19, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases had a history of contact with the Huanan Seafood Market. Here we present the results of surveillance for SARS-CoV-2 within the market. From January 1st 2020, after closure of the market, 923 samples were collected from the environment. From 18th January, 457 samples were collected from 18 species of animals, comprising of unsold contents of refrigerators and freezers, swabs from stray animals, and the contents of a fish tank. Using RT-qPCR, SARS-CoV-2 was detected in 73 environmental samples, but none of the animal samples. Three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.99% to 100% with the human isolate HCoV-19/Wuhan/IVDC-HB-01/2019. SARS-CoV-2 lineage A (8782T and 28144C) was found in an environmental sample. RNA-seq analysis of SARS-CoV-2 positive and negative environmental samples showed an abundance of different vertebrate genera at the market. In summary, this study provides information about the distribution and prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stages of the COVID-19 outbreak.

2.
Genomics ; 116(3): 110839, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38537808

RESUMO

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.


Assuntos
Proteína Smad3 , Proteína Smad3/metabolismo , Proteína Smad3/genética , Humanos , Células HEK293 , Interleucina-6/metabolismo , Interleucina-6/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Transdução de Sinais
3.
Genomics ; 116(3): 110847, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38685287

RESUMO

BACKGROUND: Bufo gargarizans Cantor, a widely distributed amphibian species in Asia, produces and releases toxins through its retroauricular and granular glands. Although various tissues have been sequenced, the molecular mechanisms underlying the toxin production remain unclear. To elucidate these mechanisms, abdominal skin (non-toxic secretory glands) and retroauricular gland (toxic secreting glands) samples were collected at different time points (3, 6, 12, 24, and 36 months) for RNA sequencing (RNA-seq) and analysis. RESULTS: In comparison to the S group during the same period, a total of 3053, 3026, 1516, 1028, and 2061 differentially expressed genes (DEGs) were identified across five developmental stages. Gene Ontology (GO) analysis revealed that DEGs were primarily enriched in biological processes including cellular processes, single-organism processes, metabolic processes, and biological regulation. In terms of cellular components, the DEGs were predominantly localized in the cell and cell parts, whereas molecular function indicated significant enrichment in binding and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the metabolism and synthesis of various substances, such as lipid metabolism, cofactor and vitamin metabolism, tryptophan metabolism, steroid biosynthesis, and primary bile acid biosynthesis, were accompanied by the development of toads. Additionally, using trend analysis, we discovered candidate genes that were upregulated in the retroauricular glands during development, and the abundance of these genes in the abdominal skin was extremely low. Finally, we identified 26 genes that are likely to be involved in toxin production and that are likely to be involved in toxin anabolism. CONCLUSION: Overall, these results provide new insights into the genes involved in toxin production in B. gargarizans, which will improve our understanding of the molecular mechanisms underlying toxigenic gene expression.


Assuntos
Bufonidae , Animais , Bufonidae/genética , Bufonidae/metabolismo , Bufonidae/crescimento & desenvolvimento , Transcriptoma , RNA-Seq , Análise de Sequência de RNA , Análise Espaço-Temporal
4.
Nano Lett ; 24(38): 11873-11881, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39225707

RESUMO

Quasi-two-dimensional (Q-2D) perovskites show great potential in the field of photonic and optoelectronic device applications. However, defects and local lattice dislocation still limit performance and stability improvement by nonradiative recombination, unpreferred phase distribution, and unbonded amines. Here, a low-temperature synergistic strategy for both reconstructing and solidifying the perovskite top and buried interface is developed. By post-treating the 1,4-phenylenedimethanammonium (PDMA) based (PDMA)MA4Pb5I16 films with cesium acetate (CsAc) before thermal annealing, a condensation reaction between R-COO- and -NH2 and ion exchange between Cs+ and MA+ occur. It converts the unbonded amines to amides and passivates uncoordinated Pb2+. Meanwhile, it adjusts film composition and improves the phase distribution without changing the out-of-plane grain orientation. Consequently, performance of 18.1% and much-enhanced stability (e.g., stability for photo-oxygen increased over 10 times, light-thermal for T90 over 4 times, and reverse bias over 3 times) of (PDMA)MA4Pb5I16 perovskite solar cells are demonstrated.

5.
J Am Chem Soc ; 146(1): 437-449, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38158611

RESUMO

Harnessing quantum confinement (QC) effects in semiconductors to retard hot carrier cooling (HCC) is an attractive approach for enabling efficient hot carrier extraction to overcome the Shockley-Queisser limit. However, there is a debate about whether halide perovskite nanocrystals (PNCs) can effectively exploit these effects. To address this, we utilized pump-probe and multipulse pump-push-probe spectroscopy to investigate HCC behavior in PNCs of varying sizes and cation compositions. Our results validate the presence of an intrinsic phonon bottleneck with clear manifestations of QC effects in small CsPbBr3 PNCs exhibiting slower HCC rates compared to those of larger PNCs. However, the replacement of inorganic Cs+ with organic cations suppresses this intrinsic bottleneck. Furthermore, PNCs exhibit distinct size-dependent HCC behavior in response to changes in the cold carrier densities. We attribute this to the enhanced exciton-exciton interactions in strongly confined PNCs that facilitate Auger heating. Importantly, our findings dispel the existing controversy and provide valuable insights into design principles for engineering QC effects in PNC hot carrier applications.

6.
Breast Cancer Res Treat ; 204(1): 89-105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38066250

RESUMO

PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Terapia Neoadjuvante/efeitos adversos , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico
7.
Cardiovasc Diabetol ; 23(1): 6, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172936

RESUMO

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants. METHODS: After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes. RESULTS: During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19-1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10-1.25) and 1.25 (1.15-1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs. CONCLUSION: Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.


Assuntos
Doenças Cardiovasculares , Humanos , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Jejum , Glucose , Triglicerídeos , Glicemia , Fatores de Risco , Biomarcadores , Medição de Risco
8.
Opt Lett ; 49(20): 5901-5904, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404567

RESUMO

Optical chaos communication has a physical-layer security advantage but defends passively against a malicious attack. Here, we conduct a proof-of-concept experiment of detecting the attack proactively by observing performance degradation in optical chaos communication tapped with fiber bending. Influences of the curvature radius of the bent fiber on a chaos synchronization coefficient and bit error rate are investigated. Results show that the synchronization coefficient decreases from 0.958 to 0.904 and the bit error rate increases from 1.31 × 10-4 to 1.73 × 10-3 under a curvature radius of 10 mm, revealing the attack. Bending fiber to this extent leads to a power loss of 1.81%, which is difficult to detect by the optical time-domain reflectometer but causes significant interference to chaos communication due to the concurrent change in the light polarization, jointly decreasing the effective optical injection strength for yielding chaos synchronization.

9.
Chemistry ; : e202403296, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39502015

RESUMO

In field of electrochemistry, there has been a growing interest in the potential applications of proton-conducting metal-organic frameworks (MOFs). Therefore, how to design and synthesize MOFs with high proton conductivity is considered crucial. In this study, two examples of nitro-containing Cd-based MOFs, MOF-1 {[Cd3(TIPE)1.5(NO3)5Cl(H2O)2]·17H2O}n and MOF-2 {[Cd(TIPE)0.5(nip)]·10H2O}n (TIPE=1,1,2,2-tetrakis(4-(1H-imidazole-1-yl)phenyl)ethene, H2nip=5-Nitroisophthalic Acid), had been successfully designed and synthesized, and their proton-conducting properties were thoroughly investigated. Notably, both materials displayed peak proton conductivity at 98% RH and 90 °C, exhibiting values of 9.13 × 10-3 and 3.00 × 10-3 S∙cm-1 for MOF-1 and MOF-2, respectively. The plausible proton conduction pathways and mechanisms were elucidated through structural analyses, water vapor adsorption studies, and the determination of activation energy (Ea) values. It was found that the difference in proton conductivity between MOF-1 and MOF-2 was mainly associated with the different water absorption rates of the samples. The uniqueness of this study was that for the first time conducted an in-depth study of the role of nitrate in proton conduction, providing new ideas for designing materials with excellent proton conductivity.

10.
Inorg Chem ; 63(8): 3870-3881, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38356223

RESUMO

Metal-organic frameworks (MOFs) have shown promising potential as proton-conducting materials due to their tunable structures and high porosity. In this study, two novel MOFs had been successfully synthesized, one containing sulfate groups (MOF-1; [Zn4(TIPE)2(SO4)4(H2O)]·5H2O) and the other containing sulfonate groups (MOF-2; [Zn2(TIPE)(5-sip)(NO3)0.66]·0.34NO3·17.5H2O) (TIPE = 1,1,2,2-tetrakis(4-(1H-imidazole-1-yl)phenyl)ethene, H35-sip = 5-sulfoisophthalicacid), and the effect of the two groups on the proton conductivity of Zn-based MOFs had been investigated and compared for the first time. The proton conductivity of these MOFs was systematically measured at different temperatures and humidity conditions. Remarkably, the results revealed significant differences in proton conductivity between the two sets of MOFs. At 90 °C and 98% RH, MOF-1 and MOF-2 achieved optimal proton conductivity of 4.48 × 10-3 and 5.69 × 10-2 S·cm-1, respectively. This was due to the structural differences arising from the presence of different functional groups, which subsequently affected the porosity and hydrophilicity, thereby influencing the proton conductivity. Overall, this comparative study revealed the influence of sulfate and sulfonate groups on the proton conductivity of Zn-based MOFs. This research provided a feasible idea for the development of advanced MOF materials with enhanced proton conductivity and opened up new possibilities for their application in proton devices.

11.
Nanotechnology ; 36(3)2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39433058

RESUMO

Investigating high-efficiency oxygen reduction reaction (ORR) catalysts is one of the most effective methods for addressing the sluggish kinetics at the fuel cell cathode. Bimetallic three-dimensional porous materials have garnered significant attention due to their diverse structures, large specific surface area and synergistic catalytic effects. Herein, we synthesized a bimetallic three-dimensional porous dodecahedral structure, Mn/Co-C-N, derived from MOF using a straightforward approach. Experimental reults confirm that the strategic incorporation of Mn enhances the electrocatalytic activity for ORR. Meanwhile, the synergistic effects of Mn and Co, as well as the advantages of the dodecahedral structure for expediting electron transfer, all contribute to the exceptional ORR performance. Arc testing in an alkaline electrolyte reveals that the initial potential (Eonset) and the half-wave potential (E1/2) are 0.89 V and 0.80 V, closely approximating those of commercial Pt/C (20 wt%). Following 10 000 stability test cycles, the half-wave potential exhibits a mere 8 mV change, confirming its remarkable stability.

12.
Bioorg Chem ; 143: 106998, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38035513

RESUMO

Androgen receptor (AR) plays a crucial role in various physiological processes. Dysregulation of AR signaling has been implicated in several diseases, such as prostate cancer and androgenetic alopecia. Therefore, the development of drugs that specifically target AR has gained significant attention in the field of drug discovery. This review provides an overview of the synthetic routes of clinically approved small molecule drugs targeting AR and discusses the clinical applications of these drugs in the treatment of AR-related diseases. The review also highlights the challenges and future perspectives in this field, including the need for improved drug design and the exploration of novel therapeutic targets. Through an integrated analysis of the therapeutic applications, synthetic methodologies, and mechanisms of action associated with these approved drugs, this review facilitates a holistic understanding of the versatile roles and therapeutic potential of AR-targeted interventions. Overall, this comprehensive review serves as a valuable resource for medicinal chemists interested in the development of small-molecule drugs targeting AR.


Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Descoberta de Drogas , Desenho de Fármacos , Transdução de Sinais
13.
J Chem Phys ; 160(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38189618

RESUMO

The sluggish oxygen evolution reaction (OER) in overall electrocatalytic water splitting poses a significant challenge in hydrogen production. A series of transition metal phosphides are emerging as promising electrocatalysts, effectively modulating the charge distribution of surrounding atoms for OER. In this study, a highly efficient OER electrocatalyst (CoP-CNR-CNT) was successfully synthesized through the pyrolysis and phosphatization of a Co-doped In-based coordination polymer, specifically InOF-25. This process resulted in evenly dispersed CoP nanoparticles encapsulated in coordination polymer-derived carbon nanoribbons. The synthesized CoP-CNR-CNT demonstrated a competitive OER activity with a smaller overpotential (η10) of 295.7 mV at 10 mA cm-2 and a satisfactory long-term stability compared to the state-of-the-art RuO2 (η10 = 353.7 mV). The high OER activity and stability can be attributed to the high conductivity of the carbon network, the abundance of CoP particles, and the intricate nanostructure of nanoribbons/nanotubes. This work provides valuable insights into the rational design and facile preparation of efficient non-precious metal-based OER electrocatalysts from inorganic-organic coordination polymers, with potential applications in various energy conversion and storage systems.

14.
J Nanobiotechnology ; 22(1): 212, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689294

RESUMO

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.


Assuntos
Alendronato , Ouro , Nanopartículas Metálicas , Osteoporose , Ácido Tióctico , Animais , Alendronato/química , Alendronato/farmacologia , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Ouro/química , Osteoporose/tratamento farmacológico , Camundongos , Nanopartículas Metálicas/química , Feminino , Osteogênese/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Tamanho da Partícula
15.
Lipids Health Dis ; 23(1): 357, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39487494

RESUMO

OBJECTIVE: The study aims to investigate the associations of triglyceride glucose (TyG), TyG combined with body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and the risk of mild cognitive impairment (MCI) in individuals without diabetes aged 45 and above. METHODS: The most recent data in this study were from a cohort study, which sourced samples from the China Health and Retirement Longitudinal Study, spanning 2011 to 2018. The four indices' associations with MCI risk were analyzed using logistic regression. The predictive capacity was measured using the receiver operating characteristic (ROC) curve. RESULTS: Over a 7-year follow-up, 1,261 individuals (31.34%) of the 4,027 participants developed MCI. Logistic regression analysis revealed significant associations between these surrogate indices and MCI. The findings for the highest quartile compared with the lowest quartile were as follows: TyG: 1.24 (95% CI: 1.02, 1.49); TyG-BMI: 1.38 (95% CI: 1.13, 1.68); METS-IR: 1.50 (95% CI: 1.09, 2.06); TG/HDL-C: 1.34 (95% CI: 1.10, 1.64). ROC analysis revealed that TyG, TyG-BMI, TG/HDL-C, and METS-IR demonstrated excellent discriminatory power for MCI, with area under the curve (AUC) values of 0.82 (95% CI: 0.80, 0.83), 0.82 (95% CI: 0.80, 0.83), 0.83 (95% CI: 0.80, 0.84), and 0.83 (95% CI: 0.80, 0.84), respectively. The four indices showed stronger ability to predict MCI risk in females compared to males. CONCLUSION: Elevated levels of four indices are positively correlated with MCI risk. TyG-BMI and METS-IR demonstrate stronger capabilities in identifying MCI across both male and female populations. This suggests that early intervention in patients with elevated IR surrogate indices may help reduce the MCI.


Assuntos
Índice de Massa Corporal , HDL-Colesterol , Disfunção Cognitiva , Resistência à Insulina , Triglicerídeos , Humanos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Triglicerídeos/sangue , China/epidemiologia , HDL-Colesterol/sangue , Curva ROC , Glicemia/metabolismo , Fatores de Risco , Biomarcadores/sangue , Estudos Longitudinais , Modelos Logísticos , População do Leste Asiático
16.
Am J Respir Crit Care Med ; 208(10): 1115-1125, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713301

RESUMO

Rationale: Mounting evidence demonstrates a role for extracellular vesicles (EVs) in driving lung disorders, such as chronic obstructive pulmonary disease (COPD). Although cigarette smoke (CS) is the primary risk factor for COPD, a link between CS and the EVs that could lead to COPD is unknown. Objective: To ascertain whether exposure to CS elicits a proteolytic EV signature capable of driving disease pathogenesis. Methods: Protease expression and enzymatic activity were measured in EVs harvested from the BAL fluid of smoke-exposed mice and otherwise healthy human smokers. Pathogenicity of EVs was examined using pathological tissue scoring after EV transfer into naive recipient mice. Measurements and Main Results: The analyses revealed a unique EV profile defined by neutrophil- and macrophage-derived EVs. These EVs are characterized by abundant surface expression of neutrophil elastase (NE) and matrix metalloproteinase 12 (MMP12), respectively. CS-induced mouse or human-derived airway EVs had a robust capacity to elicit rapid lung damage in naive recipient mice, with an additive effect of NE- and MMP12-expressing EVs. Conclusions: These studies demonstrate the capacity of CS to drive the generation of unique EV populations containing NE and MMP12. The coordinated action of these EVs is completely sufficient to drive emphysematous disease, and their presence could operate as a prognostic indicator for COPD development. Furthermore, given the robust capacity of these EVs to elicit emphysema in naive mice, they provide a novel model to facilitate preclinical COPD research. Indeed, the development of this model has led to the discovery of a previously unrecognized CS-induced protective mechanism against EV-mediated damage.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Animais , Camundongos , Peptídeo Hidrolases/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Pulmão , Enfisema Pulmonar/etiologia , Elastase Pancreática/metabolismo , Fumar/efeitos adversos , Modelos Animais de Doenças
17.
Lifetime Data Anal ; 30(4): 721-741, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38805094

RESUMO

Panel count regression is often required in recurrent event studies, where the interest is to model the event rate. Existing rate models are unable to handle time-varying covariate effects due to theoretical and computational difficulties. Mean models provide a viable alternative but are subject to the constraints of the monotonicity assumption, which tends to be violated when covariates fluctuate over time. In this paper, we present a new semiparametric rate model for panel count data along with related theoretical results. For model fitting, we present an efficient EM algorithm with three different methods for variance estimation. The algorithm allows us to sidestep the challenges of numerical integration and difficulties with the iterative convex minorant algorithm. We showed that the estimators are consistent and asymptotically normally distributed. Simulation studies confirmed an excellent finite sample performance. To illustrate, we analyzed data from a real clinical study of behavioral risk factors for sexually transmitted infections.


Assuntos
Algoritmos , Simulação por Computador , Modelos Estatísticos , Humanos , Infecções Sexualmente Transmissíveis , Análise de Regressão , Fatores de Tempo
18.
Entropy (Basel) ; 26(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38785654

RESUMO

We proposed and verified a scheme of chaos synchronization for integrated five-section semiconductor lasers with matching parameters. The simulation results demonstrated that the integrated five-section semiconductor laser could generate a chaotic signal within a large parameter range of the driving currents of five sections. Subsequently, chaos synchronization between two integrated five-section semiconductor lasers with matched parameters was realized by using a common noise signal as a driver. Moreover, it was found that the synchronization was sensitive to the current mismatch in all five sections, indicating that the driving currents of the five sections could be used as keys of chaotic optical communication. Therefore, this synchronization scheme provides a candidate to increase the dimension of key space and enhances the security of the system.

19.
Int Ophthalmol ; 44(1): 342, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103732

RESUMO

PURPOSE: Evaluate and analyze the efficacy of inferior oblique belly transposition (IOBT) in treating adult patients with diplopia and small-angle hypertropia caused by mild to moderate inferior oblique overaction (IOOA) secondary to acquired superior oblique palsy (SOP). METHODS: Nine adult patients with diplopia and small-angle hypertropia associated with mild to moderate IOOA secondary to unilateral acquired SOP were included in the current retrospective study. All patients received the IOBT procedure between February 2019 and May 2023 at The Second People's Hospital of Jinan and were followed up for more than 6 months after the surgery. During the procedure, the belly of the inferior oblique muscle was fixed to the sclera at 5 mm posterior to the temporal insertion of the inferior rectus muscle. The following indicators were reviewed pre- and post-surgery: the vertical deviation (VD) in the primary position and in the Bielschowsky test, the fovea disc angle (FDA) of the affected eye, changes in IOOA, and diplopia. RESULTS: After IOBT, the VD in the primary position decreased from 7.22△ ± 1.72△ (range 4△-10△) to 1.22△ ± 1.30△ (range 0△-3△). The VD in the Bielschowsky test decreased from 13.00△ ± 1.80△ to 3.22△ ± 1.09△. The FDA decreased from 10.02° ± 3.34° to 6.26° ± 1.91°. The grade of IOOA was reduced from 2.00 (1.00, 2.00) to 0.00 (0.00, 1.00). All changes were statistically significant (P < 0.001 or P = 0.006). Diplopia was resolved completely for all patients. CONCLUSIONS: IOBT can effectively treat adults with diplopia and small-angle hypertropia caused by mild to moderate IOOA secondary to acquired SOP.


Assuntos
Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Humanos , Estudos Retrospectivos , Músculos Oculomotores/cirurgia , Músculos Oculomotores/fisiopatologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos/métodos , Estrabismo/cirurgia , Estrabismo/fisiopatologia , Estrabismo/etiologia , Visão Binocular/fisiologia , Movimentos Oculares/fisiologia , Diplopia/etiologia , Diplopia/cirurgia , Diplopia/fisiopatologia , Diplopia/diagnóstico , Seguimentos , Resultado do Tratamento , Adulto Jovem , Doenças do Nervo Troclear/cirurgia , Doenças do Nervo Troclear/fisiopatologia , Doenças do Nervo Troclear/diagnóstico
20.
Actas Esp Psiquiatr ; 52(5): 660-669, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39403914

RESUMO

BACKGROUND: The dorsomedial prefrontal cortex (dmPFC) is considered a crucial node in emotional and cognitive processes. Voxel-mirrored homotopic connectivity (VMHC) is a validated methodology for investigating interhemispheric coordination. This study aims to elucidate the effects of electroconvulsive therapy (ECT) on the interhemispheric connectivity of the dmPFC in patients with depression, using VMHC as a measure of bilateral neural coordination. METHODS: Thirty-three patients with depression, screened at the University of Science and Technology of China (USTC), and thirty-five patients with depression, screened at Anhui Medical University (AHMU), were selected as the subjects of this study. VMHC was employed to investigate the effects of ECT on bilateral hemispheric functional connectivity. The Hamilton Depression Rating Scale (HAMD) was used to assess depressive symptoms, and the relationships between changes in HAMD scores and VMHC values were examined. RESULTS: Following ECT, the depressive symptoms of all participants decreased (p < 0.001). The VMHC values in the dmPFC were significantly increased in both groups after ECT (p < 0.01). No significant correlation was found between the increasing VMHC values in the dmPFC and the changes in HAMD scores in depressed patients (p > 0.05). CONCLUSION: These results show that ECT regulates interhemispheric functional connectivity in depressed patients, and significantly increases the VMHC values in the dmPFC. Our findings may provide a useful method for optimizing the treatment of depression.


Assuntos
Eletroconvulsoterapia , Córtex Pré-Frontal , Humanos , Córtex Pré-Frontal/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Depressão/terapia , Imageamento por Ressonância Magnética
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