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1.
NPJ Precis Oncol ; 8(1): 84, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580746

RESUMO

Emerging studies underscore the promising capabilities of large language model-based chatbots in conducting basic bioinformatics data analyses. The recent feature of accepting image inputs by ChatGPT, also known as GPT-4V(ision), motivated us to explore its efficacy in deciphering bioinformatics scientific figures. Our evaluation with examples in cancer research, including sequencing data analysis, multimodal network-based drug repositioning, and tumor clonal evolution, revealed that ChatGPT can proficiently explain different plot types and apply biological knowledge to enrich interpretations. However, it struggled to provide accurate interpretations when color perception and quantitative analysis of visual elements were involved. Furthermore, while the chatbot can draft figure legends and summarize findings from the figures, stringent proofreading is imperative to ensure the accuracy and reliability of the content.

2.
Plast Reconstr Surg Glob Open ; 12(4): e5728, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38600966

RESUMO

Background: The skin-tarsus-skin and orbicularis-tarsus-orbicularis fixation methods are widely used in double-eyelid surgery. Both methods have limitations. In this study, the two surgical methods were integrated and applied to form a stable double eyelid that mimics the natural physiological structure with minimal visible scarring. Methods: At the inner, middle, and outer sites of the double-eyelid line, 7-0 silk sutures were passed successively through the orbicularis oculi muscle at the lower edge of the incision, the tarsus/anterior tarsus tissue, and the orbicularis oculi muscle at the upper edge of the incision, and the skin was sutured with 8-0 thread. The remaining parts were fixed with 8-0 silk sutures successively passed through the skin at the lower edge of the incision, tarsus/anterior tarsus tissue, and skin at the upper edge of the incision. Scar formation, incidence of complications, and patient satisfaction were observed and recorded during follow-up. Results: Fifty-eight patients were included. The follow-up ranged from 3 to 24 months (mean, 8 months) with 47 patients undergoing primary and 11 secondary/revision surgery. Twelve cases showed slight linear scars and in 46 cases, surgical marks were almost invisible, and there were no dynamic depressed scars. Evaluation of patient satisfaction showed high satisfaction scores (VAS score, 8.56 ±â€…0.51). The main reason for dissatisfaction was asymmetry of the double eyelid. There were no significant complications. Conclusion: A skin-tarsus-skin combined with orbicularis-tarsus-orbicularis fixation technique can produce a long-lasting, natural-looking double eyelid.

3.
Nephrology (Carlton) ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637907

RESUMO

AIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children. METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed. RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis. CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".

4.
Sensors (Basel) ; 24(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38610342

RESUMO

In the field of intelligent connected vehicles, the precise and real-time identification of speed bumps is critically important for the safety of autonomous driving. To address the issue that existing visual perception algorithms struggle to simultaneously maintain identification accuracy and real-time performance amidst image distortion and complex environmental conditions, this study proposes an enhanced lightweight neural network framework, YOLOv5-FPNet. This framework strengthens perception capabilities in two key phases: feature extraction and loss constraint. Firstly, FPNet, based on FasterNet and Dynamic Snake Convolution, is developed to adaptively extract structural features of distorted speed bumps with accuracy. Subsequently, the C3-SFC module is proposed to augment the adaptability of the neck and head components to distorted features. Furthermore, the SimAM attention mechanism is embedded within the backbone to enhance the ability of key feature extraction. Finally, an adaptive loss function, Inner-WiseIoU, based on a dynamic non-monotonic focusing mechanism, is designed to improve the generalization and fitting ability of bounding boxes. Experimental evaluations on a custom speed bumps dataset demonstrate the superior performance of FPNet, with significant improvements in key metrics such as the mAP, mAP50_95, and FPS by 38.76%, 143.15%, and 51.23%, respectively, compared to conventional lightweight neural networks. Ablation studies confirm the effectiveness of the proposed improvements. This research provides a fast and accurate speed bump detection solution for autonomous vehicles, offering theoretical insights for obstacle recognition in intelligent vehicle systems.

5.
Psychoneuroendocrinology ; 165: 107042, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38613945

RESUMO

BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.

6.
Nano Lett ; 24(15): 4485-4492, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38578031

RESUMO

Confining DNA in nanochannels is an important approach to studying its structure and transportation dynamics. Graphene nanochannels are particularly attractive for studying DNA confinement due to their atomic flatness, precise height control, and excellent mechanical strength. Here, using femtosecond laser etching and wetting transfer, we fabricate graphene nanochannels down to less than 4.3 nm in height, with the length-to-height ratios up to 103. These channels exhibit high stability, low noise, and self-cleaning ability during the long-term ionic current recording. We report a clear linear relationship between DNA length and the residence time in the channel and further utilize this relationship to differentiate DNA fragments based on their lengths, ranging widely from 200 bps to 48.5 kbps. The graphene nanochannel presented here provides a potential platform for label-free analyses and reveals fundamental insights into the conformational dynamics of DNA and proteins in confined space.


Assuntos
Grafite , Eletricidade , Condutividade Elétrica , Proteínas , DNA/química
8.
Front Neurol ; 15: 1348038, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633538

RESUMO

Background: Several studies have confirmed the direct relationship between extracellular acidification and the occurrence of pain. As an effective pain management approach, the mechanism of electroacupuncture (EA) treatment of acidification-induced pain is not fully understood. The purpose of this study was to assess the analgesic effect of EA in this type of pain and to explore the underlying mechanism(s). Methods: We used plantar injection of the acidified phosphate-buffered saline (PBS; pH 6.0) to trigger thermal hyperalgesia in male Sprague-Dawley (SD) rats aged 6-8 weeks. The value of thermal withdrawal latency (TWL) was quantified after applying EA stimulation to the ST36 acupoint and/or chemogenetic control of astrocytes in the hindlimb somatosensory cortex. Results: Both EA and chemogenetic astrocyte activation suppressed the acid-induced thermal hyperalgesia in the rat paw, whereas inhibition of astrocyte activation did not influence the hyperalgesia. At the same time, EA-induced analgesia was blocked by chemogenetic inhibition of astrocytes. Conclusion: The present results suggest that EA-activated astrocytes in the hindlimb somatosensory cortex exert an analgesic effect on acid-induced pain, although these astrocytes might only moderately regulate acid-induced pain in the absence of EA. Our results imply a novel mode of action of astrocytes involved in EA analgesia.

9.
Small ; : e2311667, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507721

RESUMO

The designing and fabricating highly active hydrogen evolution reaction (HER) electrocatalysts that can superior to Pt/C is extremely desirable but challenging. Herein, the fabrication of Ru/TiO2/N-doped carbon (Ru/TiO2/NC) nanofiber is reported as a novel and highly active HER electrocatalyst through electrospinning and subsequent pyrolysis treatment, in which Ru nanoclusters are dispersed into TiO2/NC hybrid nanofiber. As a novel support, experimental and theoretical calculation results reveal that TiO2/NC can more effectively accelerate water dissociation as well as optimize the adsorption strength of *H than TiO2 and NC, thus leading to a significantly enhanced HER activity, which merely requires an overpotential of 18 mV to reach 10 mA cm-2, outperforming Pt/C in an alkaline solution. The electrolytic cell composed of Ru/TiO2/NC nanofiber and NiFe LDH/NF can generate 500 and 1000 mA cm-2 at voltages of 1.631 and 1.753 V, respectively. Furthermore, the electrolytic cell also exhibits remarkable durability for at least 100 h at 200 mA cm-2 with negligible degradation in activity. The present work affords a deep insight into the influence of support on the activity of electrocatalyst and the strategy proposed in this research can also be extended to fabricate various other types of electrocatalysts for diverse electrocatalytic applications.

10.
Chem Sci ; 15(13): 4839-4845, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38550674

RESUMO

Herein we report the reactivity study of o-carborane-fused bis(trimethylsilyl)aminoborirane towards three different types of organic azides, i.e., aryl, alkyl, and silyl azides. The reaction with ArN3 (Ar = 2,6-iPr2C6H4, 2,6-C6H3Cl2, 2,4,6-C6H2Br3, C6F5) resulted in the cycloaddition of ArN3 to the borirane BN unit accompanied by silyl migration. Conversely, in the reaction with BnN3, only the BnN3 : borirane 1 : 2 ring expansion product was obtained. Finally, the reaction with Me3SiN3 resulted in a formal nitrene insertion product under thermal conditions. All of the newly obtained o-carborane-fused BN-containing heterocycles were fully characterized, and the mechanism of these substituent-dependent reactions was studied using DFT calculations.

11.
J Clin Virol ; 171: 105662, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38432097

RESUMO

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.


Assuntos
Varíola dos Macacos , Minorias Sexuais e de Gênero , Masculino , Animais , Humanos , Varíola dos Macacos/diagnóstico , Varíola dos Macacos/tratamento farmacológico , Varíola dos Macacos/epidemiologia , Vírus da Varíola dos Macacos/genética , Homossexualidade Masculina , Zoonoses
12.
J Orthop Surg Res ; 19(1): 162, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429811

RESUMO

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Humanos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Gravidade do Paciente , Curva ROC , RNA Mensageiro , Quimiocina CXCL13
13.
Proc Natl Acad Sci U S A ; 121(11): e2400272121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437534

RESUMO

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.


Assuntos
Barreira Hematoencefálica , AVC Isquêmico , Animais , Humanos , Camundongos , Atrofia , Células Endoteliais , Endotélio , Peroxirredoxinas
14.
Biofabrication ; 16(2)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38507789

RESUMO

Corneal damage contributes to blindness in millions of people. Simulating natural corneas with artificial corneas is challenging due to material and manufacturing limitations, including poor mechanical properties, complex manufacturing processes, and ocular histocompatibility. In this study, electrospun micro-nanofibrous decellularized extracellular matrix (dECM) is combined with digital light processing 3D bioprinting and validated as a bioartificial cornea for the first time. Electrospinning gives the material a controllable shape, and the electrospun micro-nanofibrous dECM, with preserved inherent biochemical components, can better mimic the natural ECM native microenvironment. An efficient platform can be developed for creating novel structural materials, when combined with intelligent manufacturing. Artificial biological corneas developed using this method showed five-fold improvements in mechanical properties (248.5 ± 35.67 kPa vs. 56.91 ± 3.68 kPa,p< 0.001), superior guidance for cell organization and adhesion, and better maintenance of the cellular phenotype of keratocytes. In animal studies,in vivotransplantation of this artificial cornea showed better regeneration, which accelerated corneal epithelialization and maintained corneal transparency. This method has potential for biomedical applications, and bioartificial corneas manufactured by this method have ideal properties as an alternative to lamellar keratoplasty, with promise for clinical transformation.


Assuntos
Bioimpressão , Nanofibras , Animais , Humanos , Matriz Extracelular Descelularizada , Bioimpressão/métodos , Córnea , Matriz Extracelular/química , Tecidos Suporte/química , Engenharia Tecidual/métodos
15.
Heliyon ; 10(5): e26853, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439876

RESUMO

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

16.
J Immunother Cancer ; 12(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38458635

RESUMO

BACKGROUND: Programmed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC. METHODS: From July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes. RESULTS: A total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients. CONCLUSIONS: nCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined. TRIAL REGISTRATION NUMBER: NCT04437212.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Linfopenia , Trombocitopenia , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Cisplatino/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante , Carcinoma de Células Escamosas/tratamento farmacológico , Resultado do Tratamento , Recidiva Local de Neoplasia , Paclitaxel , Antígenos HLA-DR , Células Epiteliais/patologia
17.
J Nat Prod ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412432

RESUMO

Structural and functional studies of the carminomycin 4-O-methyltransferase DnrK are described, with an emphasis on interrogating the acceptor substrate scope of DnrK. Specifically, the evaluation of 100 structurally and functionally diverse natural products and natural product mimetics revealed an array of pharmacophores as productive DnrK substrates. Representative newly identified DnrK substrates from this study included anthracyclines, angucyclines, anthraquinone-fused enediynes, flavonoids, pyranonaphthoquinones, and polyketides. The ligand-bound structure of DnrK bound to a non-native fluorescent hydroxycoumarin acceptor, 4-methylumbelliferone, along with corresponding DnrK kinetic parameters for 4-methylumbelliferone and native acceptor carminomycin are also reported for the first time. The demonstrated unique permissivity of DnrK highlights the potential for DnrK as a new tool in future biocatalytic and/or strain engineering applications. In addition, the comparative bioactivity assessment (cancer cell line cytotoxicity, 4E-BP1 phosphorylation, and axolotl embryo tail regeneration) of a select set of DnrK substrates/products highlights the ability of anthracycline 4-O-methylation to dictate diverse functional outcomes.

18.
Free Radic Biol Med ; 214: 173-183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342163

RESUMO

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.


Assuntos
Lesões Encefálicas , Fluorocarbonos , Hipóxia Encefálica , Hemorragia Subaracnóidea , Animais , Humanos , Oxigênio , Fluorocarbonos/uso terapêutico , Hipóxia Encefálica/terapia
19.
Front Public Health ; 12: 1336077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389947

RESUMO

Background: The use of nonpharmaceutical interventions (NPIs) during severe acute respiratory syndrome 2019 (COVID-19) outbreaks may influence the spread of influenza viruses. This study aimed to evaluate the impact of NPIs against SARS-CoV-2 on the epidemiological features of the influenza season in China. Methods: We conducted a retrospective observational study analyzing influenza monitoring data obtained from the China National Influenza Center between 2011 and 2023. We compared the changes in influenza-positive patients in the pre-COVID-19 epidemic, during the COVID-19 epidemic, and post-COVID-19 epidemic phases to evaluate the effect of NPIs on influenza virus transmission. Results: NPIs targeting COVID-19 significantly suppressed influenza activity in China from 2019 to 2022. In the seventh week after the implementation of the NPIs, the number of influenza-positive patients decreased by 97.46% in southern regions of China and 90.31% in northern regions of China. However, the lifting of these policies in December 2022 led to an unprecedented surge in influenza-positive cases in autumn and winter from 2022 to 2023. The percentage of positive influenza cases increased by 206.41% (p < 0.001), with high positivity rates reported in both the northern and southern regions of China. Conclusion: Our findings suggest that NPIs against SARS-CoV-2 are effective at controlling influenza epidemics but may compromise individuals' immunity to the virus.


Assuntos
COVID-19 , Influenza Humana , Orthomyxoviridae , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Surtos de Doenças , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/transmissão , SARS-CoV-2 , China , Estudos Retrospectivos , Controle de Doenças Transmissíveis/métodos
20.
J Environ Sci (China) ; 141: 166-181, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38408818

RESUMO

Trace elements in atmospheric particulate matter play a significant role in air quality, human health, and biogeochemical cycles. In this study, the trace elements (Ca, Al, K, Fe, Na, Mg, Zn, Pb, Mn, Ti, Cu, Cr, Sr, Ni) in PM2.5 samples collected at the summit of Mt. Lushan were analyzed to quantify their abundance, source, transport, and health risks. During the whole sampling period, the major trace elements was Ca, Al, and K. While the trace metals with the lowest concentrations were Sr, Ni, Rb, and Cd. The trace elements were influenced by air mass transport routes, exhibiting an increasing trend of crustal elements in the northwesterly airmass and anthropogenic elements (Zn, Mn, Cu, and Ni) in the easterly air masses. Construction dust, coal + biomass burning, vehicle emission, urban nitrate-rich + urban waste incineration emissions, and soil dust + industry emissions were common sources of PM2.5 on Mt. Lushan. Different air mass transport routes had various source contribution patterns. These results indicate that trace elements at Mt. Lushan are influenced by regional anthropogenic emissions and monsoon-dominated trace element transport. The total resulting cancer risk value that these elements posed were below the acceptable risk value of 1 × 10-6, while the non-carcinogenic risk value (1.72) was higher than the safety level, suggesting that non-carcinogenic effects due to these trace elements inhalation were likely to occur. Vehicle emission and coal + biomass burning were the common dominant sources of non-cancer risks posed by trace elements at Mt. Lushan.


Assuntos
Poluentes Atmosféricos , Oligoelementos , Humanos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Oligoelementos/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Poeira/análise , China , Carvão Mineral/análise
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