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1.
J Affect Disord ; 321: 167-181, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36341802

RESUMO

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. METHOD: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. RESULTS: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. LIMITATIONS: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. CONCLUSIONS: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.


Assuntos
COVID-19 , Transtornos do Sono-Vigília , Estudantes de Medicina , Feminino , Humanos , Masculino , COVID-19/epidemiologia , Prevalência , Pandemias , Fatores de Risco , Transtornos do Sono-Vigília/epidemiologia
2.
Sci Total Environ ; 857(Pt 1): 159391, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36240915

RESUMO

Diatom-dominated biofilms and associated extracellular polymeric substances (EPS) may adapt to the stress of long-term exposure to nutrients and anthropogenic contaminants. However, such interactions in contaminated mangrove sediments have rarely been reported. Based on the in situ characterization of biofilm components and environmental factors, the present study aimed to explore the key factors involved in shaping sediment biofilms through correlational and multivariate analyses. The pennate diatom Navicula is the core taxon that plays a crucial role in balancing the abundance of Nitzschia and Cyclotella, and is the main producer of bound-polysaccharides. The taxa composition shifts in a high N/P matrix, with the populations of pennate diatoms increasing but that of centric diatoms decreasing. High nutrient concentrations yield more number of diatoms and elevated levels of EPS. Bacteria are the main consumers of EPS and tend to be more symbiotic with Nitzschia than the other two diatom taxa. Some bound-polysaccharides dominated by arabinose and glucose units are transformed into the colloidal fraction, whereas other conservative ones serve as structural materials in concert with the bound-proteins. The planktonic phase of Cyclotella breaks down the structural EPS secreted by pennate diatoms in a process that directly affects the dynamic renewal of benthic biofilms. Most heavy metals as well as bisphenol A inhibit the abundance of bacteria and diatoms but enhance most EPS fractions except bound-polysaccharides. The response of structural EPS to specific contaminants varies, exhibiting increases in Co and Ni levels but decreases in nonylphenol and methylparaben levels. The present study improves our understanding of the microbial carbon loop of benthic biofilms in mangrove ecosystems under stress by nutrients and mixed contaminants.

3.
Gene ; 849: 146906, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36162526

RESUMO

NAC transcription factors (TFs) play an important role in the plant resistant response to biotic and abiotic stresses. However, the functions of the most NAC TFs are still unknown, especially in tomato. Here, we identified and functionally characterized an NAC TFs, SlNAP1, in tomato, and found that SlNAP1 was significantly induced by salt stress. Under 150 mM NaCl treatments, morphological indexes of SlNAP1 over-expressed (SlNAP1-OE) transgenic tomato lines were significantly better than the wild-type (WT) plants. The content of Na+ in leaves and roots of SlNAP1-OE transgenic plants decreased, while the K+ content in leaves, roots, and stems increased compared with WT plants. The expression of the salt stress-related genes (NHX1, HKT1;2 and SOS1) in SlNAP1-OE plants were also significantly up-regulated under salt stress. The SOD, POD and CAT activities and the expression level of antioxidant oxidase synthesis genes of SlNAP1-OE lines were significantly increased. In addition, the SlNAP1-OE lines accumulated less MDA, H2O2 and O2•-, improved antioxidant defense systems which contributed to increase salt tolerance. In summary, our data suggest that SlNAP1 positively regulates salt tolerance in tomato by regulating ion homeostasis and ROS metabolism.


Assuntos
Lycopersicon esculentum , Tolerância ao Sal , Tolerância ao Sal/genética , Lycopersicon esculentum/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação da Expressão Gênica de Plantas , Antioxidantes , Peróxido de Hidrogênio/metabolismo , Cloreto de Sódio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Homeostase , Oxirredutases/genética , Superóxido Dismutase/genética
4.
Bioact Mater ; 21: 97-109, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36093326

RESUMO

The classical 3D-printed scaffolds have attracted enormous interests in bone regeneration due to the customized structural and mechanical adaptability to bone defects. However, the pristine scaffolds still suffer from the absence of dynamic and bioactive microenvironment that is analogous to natural extracellular matrix (ECM) to regulate cell behaviour and promote tissue regeneration. To address this challenge, we develop a black phosphorus nanosheets-enabled dynamic DNA hydrogel to integrate with 3D-printed scaffold to build a bioactive gel-scaffold construct to achieve enhanced angiogenesis and bone regeneration. The black phosphorus nanosheets reinforce the mechanical strength of dynamic self-healable hydrogel and endow the gel-scaffold construct with preserved protein binding to achieve sustainable delivery of growth factor. We further explore the effects of this activated construct on both human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) as well as in a critical-sized rat cranial defect model. The results confirm that the gel-scaffold construct is able to promote the growth of mature blood vessels as well as induce osteogenesis to promote new bone formation, indicating that the strategy of nano-enabled dynamic hydrogel integrated with 3D-printed scaffold holds great promise for bone tissue engineering.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36337580

RESUMO

Background: Chronic urticaria (CU) can severely impair the quality of life. Acupuncture and related therapies have been widely used in the treatment of CU in China. This study aimed to summarize and critically evaluate the methodological and reporting quality of relevant systematic reviews (SRs) and present objective and comprehensive evidence on the effectiveness and safety of acupuncture and related therapies for CU. Methods: Eight electronic databases were searched from inception to October 2021 for SRs examining acupuncture and related therapies for CU, and gray literature was manually searched. Two authors independently identified SRs and extracted data. The methodological and reporting quality of these SRs were assessed by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and preferred reporting items for SRs and meta-analyses (PRISMA, 2020), respectively. In addition, the risk of bias in systematic reviews (ROBIS) was used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to evaluate the quality of evidence for outcome measures. Results: In total, 23 SRs, including a total of 11 outcome indicators, were published before October 2021. The AMSTAR-2 results showed that the methodological quality of all SRs was critically low; items 2, 3, 7, 9, 10, and 16 were found to have particularly low quality. For PRISMA, the reporting quality of the included SRs was unsatisfactory, and major reporting flaws were observed in the search strategy, synthesis method, certainly assessment, reporting biases, registrations, and financial support of the included SRs. For ROBIS, 22 SRs (95.65%) had a high risk of bias. Among the 55 outcomes assessed using the GRADE framework, there were 3 (5.45%) outcomes with moderate-quality evidence, 6 (10.91%) outcomes with low-quality evidence, and 46 (83.64%) outcomes with very low-quality evidence. We found the moderate quality of evidence indicating that the total effective rate and curing rate of the acupuncture group were higher than those of the western medicine group, and the recurrence rate was lower than that of the western medicine group. Conclusions: Acupuncture and related therapies for the treatment of CU are supported by low-quality evidence-based medicine. However, considering the poor quality of these SRs, we suggest that studies with more rigorous designs, larger sample sizes, and higher methodological and reporting quality are necessary to provide stronger evidence. Registration. The protocol for this study has been registered (PROSPERO registration number: CRD42021259131).

6.
Front Nutr ; 9: 983038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337651

RESUMO

Background: The Geriatric Nutritional Index (GNRI) has been indicated as a nutritional index which is highly associated with complications and mortality in older hospitalized patients. Moreover, early studies had suggested that GNRI is a potential prognostic indicator for some malignances. However, the prognostic value of GNRI in esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant therapy followed by esophagectomy remains elusive. Materials and methods: This retrospective study incorporated 373 patients with ESCC who had underwent neoadjuvant therapy followed by radical esophagectomy at West China Hospital of Sichuan University between April 2011 and September 2021. The GNRI formula was: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were classified as GNRI-low (GNRI < 98.7) or GNRI high (GNRI ≥ 98.7). The association between GNRI and clinical survival status were assessed utilizing Kaplan-Meier methods and Cox regression analysis. Results: Three hundred and seventy three patients were retrospectively included in this study. 80 (21.5%) and 293 (78.5%) patients had been divided into the GNRI-low and GNRI-high groups respectively. Pathological T stage and the rate of nodal metastasis were significantly higher in the GNRI low group than in the GNRI high group (P = 0.003 and P = 0.001, respectively) among the examined demographic parameters. Furthermore, GNRI was significantly correlated with postoperative complications, patients with lower GNRI had a higher postoperative complication rate as compared with GNRI high group [Odds ratio: 2.023; 95% confidence interval (CI): 1.208-3.389; P = 0.007]. Univariate analysis of 5-year overall survival (OS) and disease-free survival (DFS) found that the rate of survival was considerably lower in the GNRI-low group than in the GNRI-high group (P < 0.001). However, multivariate analysis demonstrated that GNRI was not an independent risk factor. Conclusion: In patients with ESCC, low GNRI exhibited a poor nutritional indicator and related to postoperative complications after neoadjuvant therapy. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.

7.
Front Cardiovasc Med ; 9: 856695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337873

RESUMO

Background: Studies of ventricular arrhythmia (VA) have drawn much scholarly attention over the past two decades. Our study aimed to assess the current situation and detect the changing research trends of VA quantitatively and qualitatively. Materials and methods: All the information used in our statistical and bibliometric analysis were collected and summarized from papers retrieved from the Web of Science Core Collection (WoSCC) database on December 22, 2021 using certain criteria. Visual analytics were realized using CiteSpace, VOSviewer, the bibliometrix R package, and the bibliometric online analysis platform. Results: A total of 6,897 papers (6,711 original articles, 182 proceedings papers, three book chapters, and one data paper) were published in 796 journals that concentrated on the research areas of cardiovascular and critical care medicine. The most productive country and influential institution was the USA and the Mayo Clinic, respectively. Heart Rhythm (551 articles and 8,342 local citations) published the most manuscripts. The keyword co-occurrence and co-citation network of references analyses revealed that the most popular terms were ventricular tachycardia, ventricular fibrillation, catheter ablation, implantable cardioverter defibrillator (ICD), and sudden cardiac death (SCD). Further, the burst detection analysis demonstrated that topics strongly associated with clinical prognosis, such as meta-analysis, long-term outcomes, and impact, were new concerns. Conclusion: Our study offers a comprehensive picture of VA research and provides profound insights into the current research status. Moreover, we show that new topics within the VA research field have focused more on prognosis and evidence-based clinical guidelines.

8.
Front Oncol ; 12: 955866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338711

RESUMO

To establish a multidimensional nomogram model for predicting progression-free survival (PFS) and risk stratification in patients with advanced nasopharyngeal carcinoma (NPC). This retrospective cross-sectional study included 156 patients with advanced NPC who underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Radiomic features were extracted from the efflux rate constant (Ktrans ) and extracellular extravascular volume (Ve ) mapping derived from DCE-MRI. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied for feature selection. The Radscore was constructed using the selected features with their respective weights in the LASSO Cox regression analysis. A nomogram model combining the Radscore and clinical factors was built using multivariate Cox regression analysis. The C-index was used to assess the discrimination power of the Radscore and nomogram. The Kaplan-Meier method was used for survival analysis. Of the 360 radiomic features, 28 were selected (7, 6, and 15 features extracted from Ktrans , Ve, and Ktrans +Ve images, respectively). The combined Radscore k trans +Ve (C-index, 0.703, 95% confidence interval [CI]: 0.571-0.836) showed higher efficacy in predicting the prognosis of advanced NPC than Radscore k trans (C-index, 0.693; 95% CI, 0.560-0.826) and Radscore Ve (C-index, 0.614; 95% CI, 0.481-0.746) did. Multivariable Cox regression analysis revealed clinical stage, T stage, and treatment with nimotuzumab as risk factors for PFS. The nomogram established by Radscore k trans +Ve and risk factors (C-index, 0.732; 95% CI: 0.599-0.864) was better than Radscore k trans +Ve in predicting PFS in patients with advanced NPC. A lower Radscore k trans +Ve (HR 3.5584, 95% CI 2.1341-5.933), lower clinical stage (hazard ratio [HR] 1.5982, 95% CI 0.5262-4.854), lower T stage (HR 1.4365, 95% CI 0.6745-3.060), and nimotuzumab (NTZ) treatment (HR 0.7879, 95% CI 0.4899-1.267) were associated with longer PFS. Kaplan-Meier analysis showed a lower PFS in the high-risk group than in the low-risk group (p<0.0001). The nomogram based on combined pretreatment DCE-MRI radiomics features, NTZ, and clinicopathological risk factors may be considered as a noninvasive imaging marker for predicting individual PFS in patients with advanced NPC.

9.
Front Neurosci ; 16: 1026200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340791

RESUMO

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching. Trial registration number: [http://www.chictr.org.cn], identifier [ChiCTR1900022994].

10.
Org Lett ; 24(44): 8202-8207, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36322889

RESUMO

The asymmetric three-component rearrangement of alkenylfurans with various sulfonyl chlorides and anilines is developed via copper(I) and chiral vanadium cooperative catalysis, providing a facile access to a broad spectrum of sulfonyl-functionalized 4-aminocyclopentenones in high yields with excellent enantio- and diastereoselectivities.

11.
Front Genet ; 13: 1047435, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386793

RESUMO

Background: Immunotherapy has been a promising approach option for lung cancer. Method: All the open-accessed data was obtained from the Cancer Genome Atlas (TCGA) database. All the analysis was conducted using the R software analysis. Results: Firstly, the genes differentially expressed in lung cancer immunotherapy responders and non-responders were identified. Then, the lung adenocarcinoma immunotherapy-related genes were determined by LASSO logistic regression and SVM-RFE, respectively. A total of 18 immunotherapy response-related genes were included in our investigation. Subsequently, we constructed the logistics score model. Patients with high logistics score had a better clinical effect on immunotherapy, with 63.2% of patients responding to immunotherapy, while only 12.1% of patients in the low logistics score group responded to immunotherapy. Moreover, we found that pathways related to immunotherapy were mainly enriched in metabolic pathways such as fatty acid metabolism, bile acid metabolism, oxidative phosphorylation, and carcinogenic pathways such as KRAS signaling. Logistics score was positively correlated with NK cells activated, Mast cells resting, Monocytes, Macrophages M2, dendritic cells resting, dendritic cells activated and eosinophils, while was negatively related to Tregs, macrophages M0, macrophages M1, and mast cells activated. In addition, ERVH48-1 was screened for single-cell exploration. The expression of ERVH48-1 increased in patients with distant metastasis, and ERVH48-1 was associated with pathways such as pancreas beta cells, spermatogenesis, G2M checkpoints and KRAS signaling. The result of quantitative real-time PCR showed that ERVH48-1 was upregulated in lung cancer cells. Conclusion: Our study developed an effective signature to predict the immunotherapy response of lung cancer patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36396764

RESUMO

Microbial fuel cells (MFCs) have been demonstrated as a renewable energy strategy to efficiently recover chemical energy stored in wastewater into clean electricity, yet the limited power density limits their practical application. Here, Fe-doped carbon and nitrogen (Fe@CN) nanoparticles were synthesized by a direct pyrolysis process, which was further decorated to fabricate Fe@CN carbon paper anode. The modified Fe@CN anode with a higher electrochemically active surface area was not only benefit for the adhesion of electrochemically active microorganisms (EAMs) and extracellular electron transfer (EET) between the anode and EAMs but also selectively enriched Geobacter, a typical EAMs species. Accordingly, the MFCs with Fe@CN anode successfully achieved a highest voltage output of 792.76 mV and a prolonged stable voltage output of 300 h based on the mixed culture feeding with acetate. Most importantly, the electroactive biofilms on Fe@CN anode achieved more content ratio of proteins to polysaccharides (1.40) in extracellular polymeric substances for the balance between EET and cell protection under a harsh environment. This work demonstrated the feasibility of development on anode catalysts for the elaboration of the catalytic principle about interface modification, which may contribute to the practical application of MFC in energy generation and wastewater treatment.

14.
Ann Transl Med ; 10(20): 1102, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388818

RESUMO

Background: Childhood hand function is considered to be one of the strongest predictors of the ability to participate in daily activities as children with cerebral palsy (CP) reach adulthood. The manual ability classification system (MACS) is currently the most widely used for grading hand function in children with CP. However, the MACS method is subjective and may be affected by the raters' experience. Hand knob is an important control center for hand movement. Therefor this study aimed to develop and validate an objective model for hand function estimation in children with CP and visualize it as a nomogram. Methods: A total of 70 Children (2-12 years old) with CP underwent magnetic resonance imaging (MRI) scanning, MACS assessment. According to MACS, children with CP were divided into mild impairment group (grade I-III) and severe impairment group (grade IV-V). Hand function prediction models based on (I) hand knob score, (II) clinical features, and (III) the combination of clinical features and hand knob score were developed and validated separately. The models were subjected to stepwise regression according to the maximum likelihood method, and the Akaike information criterion was used to select the best model. Model discrimination was assessed using receiver operating characteristic (ROC) and calibration curves. The nomogram was finally built according to the best model. Results: The area under the curve (AUC) of the hand knob score model in the training set was 0.752, the clinical features model was 0.819, and the hand knob score and clinical features combined model was 0.880. The AUC of the hand knob score model in the validation set was 0.765, the clinical features model was 0.782, and the combined model was 0.894. The best model was the hand knob score-clinical features combined model, and the nomogram finally incorporated two assessment items: the hand knob score and white matter injury. The estimated probability of hand function injury degree of the combined model displayed good agreement with the actual occurrence probability. Conclusions: The hand knob score-clinical features combined model can be used to preliminarily assess the degree of hand impairment in children with CP, with good calibration.

15.
Small ; : e2204694, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36403215

RESUMO

Disturbed blood flow induces endothelial pro-inflammatory responses that promote atherogenesis. Nanoparticle-based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical-step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk-shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro-atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk-shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk-shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti-inflammatory and anti-atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than "naked" DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36379107

RESUMO

Syringae Folium (SF) is a traditional Chinese medicine with excellent antibacterial, anti-inflammatory, and antiviral properties. It is widely distributed in northeast China and has three origins. However, the differences between the three origins have never been compared. Here, we used the five-wavelength fusion HPLC fingerprint technique combined with chemometric analysis and the comprehensive quantitative analysis of active constituents to evaluate the quality of SF from different origins, localities, and harvesting times. As a result, SF from different origins and localities showed no differences by similarity analysis, chemometric analysis, and quantitative analysis, whereas the harvesting time was found to be the key factor inducing the variation of the SF composition. In summary, the differences in origins and localities would not cause apparent disparities, while the harvest time should be considered in the SF development and application.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36360834

RESUMO

INTRODUCTION: Electronic cigarettes are the most popular tobacco product among U.S. youth, and over 80% of current youth users of e-cigarettes use flavored e-cigarettes, with fruit, mint/menthol, and candy/sweets being the most popular flavors. A number of new e-liquid flavors are currently emerging in the online e-cigarette market. Menthol and other flavored e-cigarettes could incentivize combustible tobacco smokers to transition to e-cigarette use. METHODS: From February to May 2021, we scraped data of over 14,000 e-liquid products, including detailed descriptions of their flavors, from five national online vape shops. Building upon the existing e-liquid flavor wheel, we expanded the semantic databases (i.e., key terms) to identify flavors using WordNet-a major database for keyword matching and group discussion. Using the enriched databases, we classified 14,000+ e-liquid products into the following 11 main flavor categories: "fruit", "dessert/candy/sweets", "coffee/tea", "alcohol", "other beverages", "tobacco", "mint/menthol", "nuts", "spices/pepper", "other flavors", and "unspecified flavor". RESULTS: We find that the most prominent flavor sold in the five online vape shop in 2021 was fruit flavored products, followed by dessert/candy/other sweets. Online vendors often label a product with several flavor profiles, such as fruit and menthol. CONCLUSIONS: Given that online stores market products with multiple flavor profiles and most of their products contain fruit flavor, the FDA may have issued marketing denial orders to some of these products. It is important to further examine how online stores respond to the FDA flavor restrictions (e.g., compliance or non-compliance).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adolescente , Humanos , Mentol , Aromatizantes/análise
18.
Acta Pharmacol Sin ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357669

RESUMO

Dopaminergic neuron degeneration is a hallmark of Parkinson's disease (PD). We previously reported that the inactivation of von Hippel‒Lindau (VHL) alleviated dopaminergic neuron degeneration in a C. elegans model. In this study, we investigated the specific effects of VHL loss and the underlying mechanisms in mammalian PD models. For in vivo genetic inhibition of VHL, AAV-Vhl-shRNA was injected into mouse lateral ventricles. Thirty days later, the mice received MPTP for 5 days to induce PD. Behavioral experiments were conducted on D1, D3, D7, D14 and D21 after the last injection, and the mice were sacrificed on D22. We showed that knockdown of VHL in mice significantly alleviated PD-like syndromes detected in behavioral and biochemical assays. Inhibiting VHL exerted similar protective effects in MPP+-treated differentiated SH-SY5Y cells and the MPP+-induced C. elegans PD model. We further demonstrated that VHL loss-induced protection against experimental parkinsonism was independent of hypoxia-inducible factor and identified the Dishevelled-2 (DVL-2)/ß-catenin axis as the target of VHL, which was evolutionarily conserved in both C. elegans and mammals. Inhibiting the function of VHL promoted the stability of ß-catenin by reducing the ubiquitination and degradation of DVL-2. Thus, in vivo overexpression of DVL-2, mimicking VHL inactivation, protected against PD. We designed a competing peptide, Tat-DDF-2, to inhibit the interaction between VHL and DVL-2, which exhibited pharmacological potential for protection against PD in vitro and in vivo. We propose the therapeutic potential of targeting the interaction between VHL and DVL-2, which may represent a strategy to alleviate neurodegeneration associated with PD.

19.
J Am Chem Soc ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416740

RESUMO

Terpene cyclases (TCs), extraordinary enzymes that create the structural diversity seen in terpene natural products, are traditionally divided into two classes, class I and class II. Although the structural and mechanistic features of class I TCs are well-known, the corresponding details in class II counterparts have not been fully characterized. Here, we report the genome mining discovery and structural characterization of two class II sesquiterpene cyclases (STCs) from Streptomyces. These drimenyl diphosphate synthases (DMSs) are the first STCs shown to possess ß,γ-didomain architecture. High-resolution X-ray crystal structures of DMS from Streptomyces showdoensis (SsDMS) in complex with both a farnesyl diphosphate and Mg2+ unveiled an induced-fit mechanism, with an unprecedented Mg2+ binding mode, finally solving one of the lingering questions in class II TC enzymology. This study supports continued genome mining for novel bacterial TCs and provides new mechanistic insights into canonical class II TCs that will lead to advances in TC engineering and synthetic biology.

20.
Dev Comp Immunol ; 139: 104587, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36370908

RESUMO

The mucosal barriers of a lamb's nasal cavity are composed of a multi-layer barrier designed to protect against the invasion of harmful microorganisms. However, despite the protective measures, respiratory pathogens still infect the sheep from the nasal cavity. Therefore, our study aimed to investigate the characteristics of lamb's nasal cavity barrier at different developmental stages. For nasal histological characteristics, our study revealed that the conchoidal curvature of the inferior nasal conch and the number of glands significantly increased with lamb development. For nasal mucosal barrier characteristics, physical and immune barriers were carefully explored. Initially, we observed that the thickness and proliferative capacity of nasal epithelial significantly increased from fetal to 21 days, which then decreased at 60 days. Then, our study showed that the number of goblet cells (GCs) of 21 days old lamb was significantly higher than in other stages of development. Besides, we found that the number of nasal immune cells, such as dendritic cells, CD3+ T cells, IgA+ B cells, and nasal-associated lymphoid tissue (NALT), were all significantly increased not only from the proximal to distal side in the nasal cavity but also with their age. Totally, our study revealed various characteristics of the mucosal barriers of a lamb's nasal cavity, which provide a reference for explaining the susceptibility of respiratory tract infection in lambs.

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