RESUMEN
BACKGROUND: The main causes of abnormal white matter development (periventricular leukomalacia) in premature infants are perinatal inflammation and the consequent oxidant/antioxidant imbalance in oligodendrocyte precursor cells (OPCs); however, the underlying mechanisms remain largely unclear. In this work, a rat model of prenatal inflammation was used to examine the mechanism by which artemisinin (ART) protects against white matter dysplasia. METHODS: We established a primary OPC model and rat model of perinatal inflammation. ART was identified from the FDA-approved medicinal chemical library to be beneficial for treating OPC inflammation in model systems. Based on bioinformatics analysis of protein interactions and molecular docking analysis, we further identified the possible targets of ART and evaluated its specific effects and the underlying molecular mechanisms in vivo and in vitro. RESULTS: Following inflammatory stimulation, ART strongly promoted the maturation of OPCs and the development of white matter in the brain. A Cellular thermal shift assay (CETSA) demonstrated that interleukin-1 receptor-associated kinase-4 (IRAK-4) and interleukin-1 receptor-associated kinase-1 (IRAK-1) may be targets of ART, which was consistent with the findings from molecular modelling with Autodock software. Experiments conducted both in vivo and in vitro demonstrated the activation of the IRAK-4/IRAK-1/nuclear factor kappa-B (NF-κB) pathway and the production of inflammatory factors (IL-1ß, IL-6, and TNF-α) in OPCs were greatly suppressed in the group treated with ART compared to the lipopolysaccharide (LPS)-treated group. Moreover, ART dramatically decreased reactive oxygen species (ROS) levels in OPCs while increasing nuclear factor e2-related factor 2 (Nrf2) levels. CONCLUSION: Our findings suggest that ART can significantly reduce OPC perinatal inflammation and consequent oxidative stress. The targeted inhibition of IRAK-4 and IRAK-1 by ART may be a potential therapeutic strategy for alleviating abnormalities in white matter development in premature newborns.
RESUMEN
This study investigated the influence of different temperatures (35â High temperature and average indoor ambient temperature of 25â) and lactic acid bacterial additives (Lactiplantibacillus plantarym, Lentilactobacillus buchneri, or a combination of Lactiplantibacillus plantarym and Lentilactobacillus buchneri) on the chemical composition, fermentation quality, and microbial community of alfalfa silage feed. After a 60-day ensiling period, a significant interaction between temperature and additives was observed, affecting the dry matter (DM), crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF) of the silage feed (p < 0.05). Temperature had a highly significant impact on the pH value of the silage feed (p < 0.0001). However, the effect of temperature on lactic acid, acetic acid, propionic acid, and butyric acid was not significant (p > 0.05), while the inoculation of additives had a significant effect on lactic acid, acetic acid, and butyric acid (p > 0.05). As for the dynamic changes of microbial community after silage, the addition of three kinds of bacteria increased the abundance of lactobacillus. Among all treatment groups, the treatment group using complex bacteria had the best fermentation effect, indicating that the effect of complex lactic acid bacteria was better than that of single bacteria in high temperature fermentation. In summary, this study explained the effects of different temperatures and lactic acid bacterial additives on alfalfa fermentation quality and microbial community, and improved our understanding of the mechanism of alfalfa related silage at high temperatures.
Asunto(s)
Medicago sativa , Ensilaje , Temperatura , Medicago sativa/microbiología , Ensilaje/microbiología , Fermentación , Microbiota , Lactobacillales , Ácido Láctico/metabolismoRESUMEN
Importance: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear. Objective: To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis. Design, Setting, and Participants: This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024. Exposures: Early (immediate) vs delayed (starting on day 8) antihypertensive therapy. Main Outcome and Measure: Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days. Results: Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT03479554.
Asunto(s)
Antihipertensivos , Tiempo de Tratamiento , Humanos , Femenino , Antihipertensivos/uso terapéutico , Masculino , Persona de Mediana Edad , Anciano , Tiempo de Tratamiento/estadística & datos numéricos , China/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Resultado del Tratamiento , Infarto Cerebral/tratamiento farmacológico , Factores de Tiempo , Accidente Cerebrovascular Isquémico/tratamiento farmacológicoRESUMEN
OBJECTIVES: To determine the incidence of UI (urinary incontinence) and its subtypes in hypertensive women and examine the association between hypertension and new-onset UI. STUDY DESIGN: We conducted a cohort study on women aged ≥20 years in six regions of China. This cohort study was carried out from 2014 to 2016 at baseline, with follow-up completed in 2018. Information on sociodemographic characteristics, physiological and health behaviours were collected. We calculated the standardized person-year incidence of UI in hypertensive women, and used logistic regression to evaluate the association between hypertension and UI and its subtypes. RESULTS: The standardized incidence of UI, stress UI (SUI), urgency UI (UUI), and mixed UI (MUI) in hypertensive women was 32.2, 21.9, 4.1, and 6.1 per 1000 person-years. Compared with normotensive women, the unadjusted and adjusted OR (odd ratio) for UI in hypertensive women was 2.62 (95 % confidence interval [CI], 2.16-3.18) and 1.70 (95 % CI, 1.14-2.53), respectively; The unadjusted and adjusted OR for SUI in women with hypertension was 2.44 (95 % CI, 1.92-3.09) and 2.60 (95 % CI, 1.68-4.04), respectively; The unadjusted and adjusted OR for UUI in women with hypertension was 2.80 (95 % CI, 1.79-4.37) and 0.54 (95 % CI, 0.13-3.66), respectively; The unadjusted and adjusted OR for MUI in women with hypertension was 2.49 (95 % CI, 1.92-3.09) and 0.60 (95 % CI, 0.19-1.91), respectively. CONCLUSIONS: The incidence of UI in hypertensive women was 32.2/1000 person-years. Hypertension was an independent risk factor for new-onset UI and SUI in Chinese adult women.
Asunto(s)
Hipertensión , Incontinencia Urinaria , Humanos , Femenino , Hipertensión/epidemiología , Hipertensión/complicaciones , Persona de Mediana Edad , China/epidemiología , Incidencia , Adulto , Incontinencia Urinaria/epidemiología , Estudios de Cohortes , Anciano , Factores de Riesgo , Pueblos del Este de AsiaRESUMEN
The success of the ClassSR has led to a strategy of decomposing images being used for large image SR. The decomposed image patches have different recovery difficulties. Therefore, in ClassSR, image patches are reconstructed by different networks to greatly reduce the computational cost. However, in ClassSR, the training of multiple sub-networks inevitably increases the training difficulty. Furthermore, decomposing images with overlapping not only increases the computational cost but also inevitably produces artifacts. To address these challenges, we propose an end-to-end general framework, named patches separation and artifacts removal SR (PSAR-SR). In PSAR-SR, we propose an image information complexity module (IICM) to efficiently determine the difficulty of recovering image patches. Then, we propose a patches classification and separation module (PCSM), which can dynamically select an appropriate SR path for image patches of different recovery difficulties. Moreover, we propose a multi-attention artifacts removal module (MARM) in the network backend, which can not only greatly reduce the computational cost but also solve the artifacts problem well under the overlapping-free decomposition. Further, we propose two loss functions - threshold penalty loss (TP-Loss) and artifacts removal loss (AR-Loss). TP-Loss can better select appropriate SR paths for image patches. AR-Loss can effectively guarantee the reconstruction quality between image patches. Experiments show that compared to the leading methods, PSAR-SR well eliminates artifacts under the overlapping-free decomposition and achieves superior performance on existing methods (e.g., FSRCNN, CARN, SRResNet, RCAN and CAMixerSR). Moreover, PSAR-SR saves 53%-65% FLOPs in computational cost far beyond the leading methods. The code will be made available: https://github.com/dywang95/PSAR-SR.
Asunto(s)
Artefactos , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , HumanosRESUMEN
BACKGROUND: Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. AIM: To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. RESULTS: In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). CONCLUSION: While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.
RESUMEN
Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.
RESUMEN
Background: The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population. Methods: In this baseline analysis of 498 adults (>18 years) with TB symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP as a continuous variable using generalized linear models. Results: Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4% and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART and 0.8% to 5.0% would have untreated TB at ART initiation. Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.
RESUMEN
INTRODUCTION: Postendoscopic submucosal dissection (ESD) coagulation syndrome (PECS) prevention is one of the common postoperative complications of colorectal ESD. Considering the increasing incidence of PECS, it is critical to investigate various prevention methods. The objective of this study was to evaluate the efficacy of transrectal drainage tubes (TDTs) in PECS prevention in patients following colorectal ESD. METHODS: From July 2022 to July 2023, a multicenter, randomized controlled clinical trial was conducted in 3 hospitals in China. Patients with superficial colorectal lesions ≥20 mm who had undergone ESD for a single lesion were enrolled. Initially, 229 patients were included in the study and 5 were excluded. Two hundred twenty-four were randomly assigned to the TDT and non-TDT group in the end. This open-label study utilized a parallel design with a 1:1 allocation ratio, and endoscopists and patients were not blind to the randomization, and a 24 Fr drainage tube was inserted approximately 10-15 cm above the anus after the ESD under the endoscopy and tightly attached to a drainage bag. The TDTs were removed in 1-3 days following the ESD. RESULTS: A total of 229 eligible patients were enrolled in this study, and 5 patients were excluded. Ultimately, 224 patients were assigned to the TDT group (n = 112) and non-TDT group (n = 112). The median age for the patients was 63.45 years (IQR 57-71; 59 men [52.68%]) in the TDT group and 60.95 years (IQR 54-68; 60 men [53.57%]) in the non-TDT group. Intention-to-treat analysis showed patients in the TDT group had a lower incidence of PECS than patients in the non-TDT group (7 [6.25%] vs 20 [17.86%]; relative risk, 0.350; 95% confidence interval [CI], 0.154-0.795; P = 0.008). In the subgroup analysis, TDTs were found to prevent PECS in patients of the female gender (odd ratio, 0.097; 95% CI, 0.021-0.449; P = 0.001), tumor size <4 cm (odd ratio, 0.203; 95% CI, 0.056-0.728; P = 0.011), tumor located in the left-sided colorectum (odd ratio, 0. 339 95% CI, 0.120-0.957; P = 0.035), and shorter procedure time (<45 minutes) (odd ratio, 0.316; 95% CI, 0.113-0.879; P = 0.023). The tube fell off in 1 case (0.89%) accidentally ahead of time. No TDT-related complication was observed. DISCUSSION: The results from this randomized clinical study indicate that the application of TDTs effectively reduced the incidence of PECS in patients after colorectal ESD ( chictr.org.cn Identifier: ChiCTR2200062164).
RESUMEN
Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.
Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Cobertura de Vacunación , Humanos , China , Vacunas contra la Influenza/administración & dosificación , Anciano , Gripe Humana/prevención & control , Masculino , Femenino , Cobertura de Vacunación/estadística & datos numéricos , Cobertura de Vacunación/tendencias , Anciano de 80 o más Años , Vacunación/estadística & datos numéricos , Vacunación/tendencias , Persona de Mediana EdadRESUMEN
Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor-ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.
RESUMEN
Objective: The aim of this study was to investigate the effects of Lactiplantibacillus plantarum (L. plantarum) and propionic acid (PA) on fermentation characteristics and microbial community of amaranth (Amaranthus hypochondriaus) silage with different moisture contents. Methods: Amaranth was harvested at maturity stage and prepared for ensiling. There were two moisture content gradients (80%: AhG, 70%: AhS; fresh material: FM) and three treatments (control: CK, L. plantarum: LP, propionic acid: PA) set up, and silages were opened after 60 d of ensiling. Results: The results showed that the addition of L. plantarum and PA increased lactic acid (LA) content and decreased pH of amaranth after fermentation. In particular, the addition of PA significantly increased crude protein content (p < 0.05). LA content was higher in wilted silage than in high-moisture silage, and it was higher with the addition of L. plantarum and PA (p < 0.05). The dominant species of AhGLP, AhSCK, AhSLP and AhSPA were mainly L. plantarum, Lentilactobacillus buchneri and Levilactobacillus brevis. The dominant species in AhGCK include Enterobacter cloacae, and Xanthomonas oryzae was dominated in AhGPA, which affected fermentation quality. L. plantarum and PA acted synergistically after ensiling to accelerate the succession of dominant species from gram-negative to gram-positive bacteria, forming a symbiotic microbial network centred on lactic acid bacteria. Both wilting and additive silage preparation methods increased the degree of dominance of global and overview maps and carbohydrate metabolism, and decreased the degree of dominance of amino acid metabolism categories. Conclusion: In conclusion, the addition of L. plantarum to silage can effectively improve the fermentation characteristics of amaranth, increase the diversity of bacterial communities, and regulate the microbial community and its functional metabolic pathways to achieve the desired fermentation effect.
RESUMEN
DNA methyltransferase 1 (DNMT1) is the primary enzyme responsible for maintaining DNA methylation patterns during cellular division, crucial for cancer development by suppressing tumor suppressor genes. In this study, we retained the phthalimide structure of N-phthaloyl-l-tryptophan (RG108) and substituted its indole ring with nitrogen-containing aromatic rings of varying sizes. We synthesized 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids and confirmed them as DNMT1 inhibitors through protein affinity testing, radiometric method using tritium labeled SAM, and MTT assay. Preliminary structure-activity relationship analysis revealed that introducing substituents on the carbazole ring could enhance inhibitory activity, with S-configuration isomers showing greater activity than R-configuration ones. Notably, S-3-(3,6-di-tert-butyl-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7r-S) and S-3-(1,3,6-trichloro-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7t-S) exhibited significant DNMT1 enzyme inhibition activity, with IC50 values of 8.147 µM and 0.777 µM, respectively (compared to RG108 with an IC50 above 250 µM). Moreover, they demonstrated potential anti-proliferative activity on various tumor cell lines including A2780, HeLa, K562, and SiHa. Transcriptome analysis and KEGG pathway enrichment of K562 cells treated with 7r-S and 7t-S identified differentially expressed genes (DEGs) related to apoptosis and cell cycle pathways. Flow cytometry assays further indicated that 7r-S and 7t-S induce apoptosis in K562 cells and arrest them in the G0/G1 phase in a concentration-dependent manner. Molecular docking revealed that 7t-S may bind to the methyl donor S-adenosyl-l-methionine (SAM) site in DNMT1 with an orientation opposite to RG108, suggesting potential for deeper penetration into the DNMT1 pocket and laying the groundwork for further modifications.
Asunto(s)
Carbazoles , Proliferación Celular , ADN (Citosina-5-)-Metiltransferasa 1 , Inhibidores Enzimáticos , Humanos , Relación Estructura-Actividad , Carbazoles/farmacología , Carbazoles/química , Carbazoles/síntesis química , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Indoles/farmacología , Indoles/química , Indoles/síntesis química , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Ftalimidas , Triptófano/análogos & derivadosRESUMEN
Nanohydroxyapatite (nHAp) has attracted significant attention for its tumor suppression and tumor microenvironment modulation capabilities. However, a strong tendency to aggregate greatly affects its anti-tumor efficiency. To address this issue, a hydrogel platform consisting of thiolated hyaluronic acid (HA-SH) modified nanohydroxyapatite (nHAp-HA) and HA-SH was developed for sustained delivery of nHAp for melanoma therapy. The hydrophilic and negatively charged HA-SH significantly improved the size dispersion and stability of nHAp in aqueous media while conferring nHAp targeting effects. Covalent sulfhydryl self-cross-linking between HA-SH and nHAp-HA groups ensured homogeneous dispersion of nHAp in the matrix material. Meanwhile, the modification of HA-SH conferred the targeting properties of nHAp and enhanced cellular uptake through the HA/CD44 receptor. The hydrogel platform could effectively reduce the aggregation of nHAp and release nHAp in a sustained and orderly manner. Antitumor experiments showed that the modified nHAp-HA retained the tumor cytotoxicity of nHAp in vitro and inhibited the growth of highly malignant melanomas up to 78.6% while being able to induce the differentiation of macrophages to the M1 pro-inflammatory and antitumor phenotype. This study will broaden the application of nanohydroxyapatite in tumor therapy.
Asunto(s)
Durapatita , Ácido Hialurónico , Hidrogeles , Melanoma , Durapatita/química , Durapatita/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ratones , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/metabolismo , Línea Celular Tumoral , Humanos , Receptores de Hialuranos/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Nanopartículas/química , Células RAW 264.7RESUMEN
BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.
Asunto(s)
Insectos Vectores , Animales , Humanos , Insectos Vectores/microbiología , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , China/epidemiología , Dípteros/microbiología , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Muscidae/microbiologíaRESUMEN
Reconstructive surgery plays a crucial role in addressing congenital defects, posttraumatic deformities, and related conditions, providing transformative solutions for patients. Its primary goal is to restore or enhance damaged tissue structures, improving both functionality and appearance, and empowering individuals to lead fulfilling lives. Take, for example, a female patient who experienced a nasal infection after a cat bite. Despite initial treatment, she developed severe scar contractures and excessive scar tissue within her nostrils, significantly impacting her quality of life. Seeking assistance, she consulted the authors' plastic and reconstructive surgery team. By utilizing various flap techniques, the authors embarked on the intricate journey of reconstructing her nasal framework, ultimately restoring both form and function.
RESUMEN
This study describes Impatiensyingjingensis X.Q. Song, B.N. Song & Biao Yang, sp. nov., a new species collected from the Yingjing area of the Giant Panda National Park. This new species is distributed at an altitude of 1400-2100 m, with a plant height of 30-130 cm. The flowers are purple-red or light purple red, with 3-9 flowers on each inflorescence and the dorsal auricle of the lateral united petals is thread-like and about 2 cm long, differing significantly from other species of Impatiens. Furthermore, molecular data, as well as micro-morphological evidence under SEM (of pollens), also support the establishment of the new species.
RESUMEN
Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS. Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS. Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes. Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod. Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.
An indirect comparison of ozanimod vs other oral treatments in relapsing-remitting multiple sclerosis The many treatment options available for relapsing-remitting multiple sclerosis (RRMS) make treatment decisions difficult. While direct head-to-head treatment comparisons provide useful information, these studies are not available for every pair of treatments. Indirect comparisons of published study results can help fill that evidence gap. A technique called matching-adjusted indirect comparison (MAIC) offers a statistically robust way to compare safety/efficacy outcomes from different studies by accounting for important differences across the studies. We collected data from four MAIC studies that compared 2-year treatment outcomes in patients treated with ozanimod versus those treated with fingolimod, teriflunomide, dimethyl fumarate (DMF), or ponesimod. Each study accounted for differences in age, sex, relapses within the previous year, disability status, and previous therapy use. We found ozanimod was either better than or similar to other treatments based on the outcomes measured. The annual rate of RRMS relapse was lower for patients treated with ozanimod than for patients treated with teriflunomide or DMF and similar for patients treated with ponesimod or fingolimod. Ozanimod-treated patients saw their RRMS progress at rates similar to those treated with fingolimod at 3 and 6 months and teriflunomide and DMF at 6 months; RRMS was more likely to progress at 3 months in patients treated with teriflunomide and DMF versus those treated with ozanimod. Our analyses also found that patients treated with ozanimod had lower rates of side effects, including those serious enough to cause treatment discontinuation, compared with patients receiving other treatments. By comparing findings from existing MAIC studies, we found that patients with RRMS treated with ozanimod had fewer side effects and better or similar efficacy outcomes compared with patients who received other treatments for RRMS. These findings can potentially inform treatment decisions for patients with RRMS.
RESUMEN
The management of chronic infected wounds poses significant challenges due to frequent bacterial infections, high concentrations of reactive oxygen species, abnormal immune regulation, and impaired angiogenesis. This study introduces a novel, microenvironment-responsive, dual dynamic, and covalently bonded hydrogel, termed OHA-P-TA/G/Mg2+. It is derived from the reaction of tannic acid (TA) with phenylboronic acids (PBA), which are grafted onto oxidized hyaluronic acid (OHA-P-TA), combined with GelMA (G) via a Schiff base and chemical bonds, along with the incorporation of Mg2+. This hydrogel exhibits pH and ROS dual-responsiveness, demonstrating effective antibacterial capacity, antioxidant ability, and the anti-inflammatory ability under distinct acidic and oxidative microenvironments. Furthermore, the release of Mg2+ from the TA-Mg2+ network (TA@Mg2+) promotes the transformation of pro-inflammatory M1 phenotype macrophages to anti-inflammatory M2 phenotype, showing a microenvironment-responsive response. Finally, in vivo results indicate that the OHA-P-TA/G/Mg2+ hydrogel enhances epithelial regeneration, collagen deposition, and neovascularization, showing great potential as an effective dressing for infected wound repair.