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1.
Sci Total Environ ; 857(Pt 2): 159424, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36244488

RESUMO

Biochar-derived water-soluble organic carbon (BWSOC) plays important roles in the environmental effect of biochar. The environmental behavior and fate of BWSOC are closely related to its size distribution and chemical components. However, the molecular size-dependent BWSOC components and properties remain little known. To evaluate molecular size-dependent BWSOC characteristics, BWSOC samples were prepared by pyrolyzing biomasses in air-limitation and N2-flow atmospheres at 300-600 °C and fractionated through a series of membranes with different pore sizes including 0.7 µm, 0.45 µm, 100 kDa, 10 kDa, 3 kDa, and 1 kDa. In all BWSOCs, <1 kDa and 0.45-0.7 µm fractions had the maximum abundance (mean: 40.6 %) and the minimum abundance (mean: 4.4 %), respectively. The spectral characteristics of BWSOC including polarity index, spectral slope, and humification index varied significantly with molecular size. The fluorescence excitation-emission matrix parallel factor (EEM-PARAFAC) analysis indicated that BWSOC was mainly composed of three organic components (humic-like, fulvic-like, and aromatic protein/polyphenol-like substances). Humic-like and fulvic-like substances mainly existed in <1 kDa fraction, while aromatic protein/polyphenol-like substances mainly existed in medium-size fractions (3 kDa-0.45 µm). The different locations of <1 kDa, 1 kDa-0.45 µm, and 0.45-0.7 µm fractions in EEM and PARAFAC self-organizing maps indicated self-organizing maps could effectively distinguish 0.45-0.7 µm, 1 kDa-0.45 µm, and < 1 kDa fractions via the variations of fluorescence intensity and organic components. Additionally, the distribution ratio of different molecular size fractions as well as the abundances of organic components in different molecular size fractions were strongly controlled by pyrolysis atmospheres (air-limitation and N2-flow). This study systematically clarified the organic components and properties of different molecular size fractions in BWSOC, and the results are helpful to understand the possible environmental behavior and fate of BWSOC.


Assuntos
Carbono , Substâncias Húmicas , Substâncias Húmicas/análise , Água , Polifenóis , Espectrometria de Fluorescência/métodos , Análise Fatorial
2.
Front Psychiatry ; 13: 1022881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339850

RESUMO

Background: Since February 2022, a new Omicron wave of COVID-19 emerged in Shanghai, China. Many healthcare workers came to Shanghai from hospitals of other parts of China as aid workers. Hospitals in areas with mild COVID-19 outbreaks will inevitably be understaffed, it is likely to cause job burnout of stay-behind healthcare workers. Stay-behind healthcare workers were those who had not been dispatched to support COVID-19 prevention and control in other regions. This study was designed to evaluate the burnout among stay-behind healthcare workers in the current COVID-19 Omicron wave in Taizhou, China. Methods: A population-based, anonymous, cross-sectional online survey was designed in the Wen-Juan Xing platform. The survey was sent to all stay-behind healthcare workers of the hospital (n = 1739) from April 29 to May 3, 2022. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for the burnout survey. For univariate analysis, the χ2 test and one way ANOVA were used to assess differences in categorical variables and continuous variables, respectively. The effect of independent associated risk factors on each type of burnout was examined using the multinomial logistic regression model. Results: A total of 434 participants completed the survey invitation effectively. A total of 71.2% of stay-behind healthcare workers experienced burnout during COVID-19, including 54.8% experiencing mild to moderate burnout and 16.4% experiencing severe burnout. Night shift, depression, social support, positive coping and number of children appeared to be significantly related to mild to moderate burnout. Night shift, depression, social support, positive coping, number of children, professional title, and anxiety appeared to be significantly related to severe burnout. Conclusion: Job burnout among stay-behind healthcare workers was an important problem during the current Omicron wave of COVID-19. Night shift, depression, social support, positive coping, and number of children were associated with mild to moderate and severe burnout. Anxiety and professional title were associated with severe burnout.

3.
BMC Infect Dis ; 22(1): 836, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368929

RESUMO

BACKGROUND: The COVID-19 pandemic has raised awareness of infection prevention and control. We found that the incidence of nosocomial infection in neurosurgery has changed. This study aimed to evaluate the impact of "coronavirus disease 2019 (COVID-19) prevention and control measures" on nosocomial infections in neurosurgery. METHODS: To explore changes in nosocomial infections in neurosurgery during the COVID-19 pandemic, the clinical data of inpatients undergoing neurosurgery at Taizhou Hospital of Zhejiang Province between January 1 and April 30, 2020 (COVID-19 era) were first analyzed and then compared with those from same period in 2019 (first pre-COVID-19 era). We also analyzed data between May 1 and December 31, 2020 (post-COVID-19 era) at the same time in 2019 (second pre-COVID-19 era). RESULTS: The nosocomial infection rate was 7.85% (54/688) in the first pre-COVID-19 era and 4.30% (26/605) in the COVID-19 era (P = 0.01). The respiratory system infection rate between the first pre-COVID-19 and COVID-19 eras was 6.1% vs. 2.0% (P < 0.01), while the urinary system infection rate was 1.7% vs. 2.0% (P = 0.84). Between the first pre-COVID-19 and COVID-19 eras, respiratory system and urinary infections accounted for 77.78% (42/54) vs. 46.15% (12/26) and 22.22% (12/54) vs. 46.15% (12/26) of the total nosocomial infections, respectively (P < 0.01). Between the second pre-COVID-19 and post-COVID-19 eras, respiratory system and urinary accounted for 53.66% (44/82) vs. 40.63% (39/96) and 24.39% (20/82) vs. 40.63% (39/96) of the total nosocomial infections, respectively (P = 0.02). CONCLUSIONS: The incidence of nosocomial infections in neurosurgery reduced during the COVID-19 pandemic. The reduction was primarily observed in respiratory infections, while the proportion of urinary infections increased significantly.


Assuntos
COVID-19 , Infecção Hospitalar , Neurocirurgia , Infecções Respiratórias , Infecções Urinárias , Humanos , Infecção Hospitalar/prevenção & controle , COVID-19/epidemiologia , Pandemias , Centros de Atenção Terciária , Infecções Urinárias/epidemiologia , Infecções Urinárias/complicações , Infecções Respiratórias/epidemiologia , China/epidemiologia
4.
PeerJ ; 10: e14213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389410

RESUMO

Transmission of Ross River virus (RRV) is influenced by climatic, environmental, and socio-economic factors. Accurate and robust predictions based on these factors are necessary for disease prevention and control. However, the complicated transmission cycle and the characteristics of RRV notification data present challenges. Studies to compare model performance are lacking. In this study, we used RRV notification data and exposure data from 2001 to 2020 in Queensland, Australia, and compared ten models (including generalised linear models, zero-inflated models, and generalised additive models) to predict RRV incidence in different regions of Queensland. We aimed to compare model performance and to evaluate the effect of statistical over-dispersion and zero-inflation of RRV surveillance data, and non-linearity of predictors on model fit. A variable selection strategy for screening important predictors was developed and was found to be efficient and able to generate consistent and reasonable numbers of predictors across regions and in all training sets. Negative binomial models generally exhibited better model fit than Poisson models, suggesting that over-dispersion in the data is the primary factor driving model fit compared to non-linearity of predictors and excess zeros. All models predicted the peak periods well but were unable to fit and predict the magnitude of peaks, especially when there were high numbers of cases. Adding new variables including historical RRV cases and mosquito abundance may improve model performance. The standard negative binomial generalised linear model is stable, simple, and effective in prediction, and is thus considered the best choice among all models.

5.
Clin Chim Acta ; 537: 167-172, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332668

RESUMO

OBJECTIVE: To investigate the diagnostic value of serum chitinase-3-like-1 protein (YKL-40) levels for myocardial involvement in idiopathic inflammatory myopathies (IIM). METHODS: A total of 74 patients with definite IIM who visited Jiangsu Province People's Hospital between May 2018 and January 2022 were enrolled in this retrospective study. Baseline clinical evaluation, laboratory index, electrocardiogram (ECG), echocardiography (ECHO) and cardiac magnetic resonance (CMR) parameters were collected. Serum YKL-40 of all participants was determined by ELISA. Receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of YKL-40 in assessing myocardial involvement in IIM patients. RESULTS: 1. YKL-40 concentration was significantly higher in IIM patients with myocardial injury than without myocardial injury.2. Multivariate logistic regression analysis demonstrated that serum YKL-40 was an independent risk factor for myocardial involvement in IIM.3. YKL-40 > 66.4 ng/ml (AUC = 0.85, 95 % CI 0.75-0.95) predicted myocardial injury in IIM with a sensitivity of 0.75 and specificity of 0.95. CONCLUSION: Serum YKL-40 could serve as a potential biomarker to predict myocardial injury in IIM patients.


Assuntos
Miosite , Humanos , Estudos Retrospectivos , Proteína 1 Semelhante à Quitinase-3 , Miosite/diagnóstico , Miocárdio/patologia , Coração , Biomarcadores
6.
Clin Transl Med ; 12(11): e1094, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36354147

RESUMO

Hydrogels are promising and widely utilized in the biomedical field. In recent years, the anti-inflammatory function of hydrogel dressings has been significantly improved, addressing many clinical challenges presented in ongoing endeavours to promote wound healing. Wound healing is a cascaded and highly complex process, especially in chronic wounds, such as diabetic and severe burn wounds, in which adverse endogenous or exogenous factors can interfere with inflammatory regulation, leading to the disruption of the healing process. Although insufficient wound inflammation is uncommon, excessive inflammatory infiltration is an almost universal feature of chronic wounds, which impedes a histological repair of the wound in a predictable biological step and chronological order. Therefore, resolving excessive inflammation in wound healing is essential. In the past 5 years, extensive research has been conducted on hydrogel dressings to address excessive inflammation in wound healing, specifically by efficiently scavenging excessive free radicals, sequestering chemokines and promoting M1 -to-M2 polarization of macrophages, thereby regulating inflammation and promoting wound healing. In this study, we introduced novel anti-inflammatory hydrogel dressings and demonstrated innovative methods for their preparation and application to achieve enhanced healing. In addition, we summarize the most important properties required for wound healing and discuss our analysis of potential challenges yet to be addressed.


Assuntos
Hidrogéis , Cicatrização , Humanos , Hidrogéis/farmacologia , Bandagens , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação
7.
Sci Rep ; 12(1): 19829, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400881

RESUMO

The individual prognosis of chemotherapy is quite different in non-small cell lung cancer (NSCLC). There is an urgent need to precisely predict and assess the treatment response. To develop a deep multiple-instance learning (DMIL) based model for predicting chemotherapy response in NSCLC in pretreatment CT images. Two datasets of NSCLC patients treated with chemotherapy as the first-line treatment were collected from two hospitals. Dataset 1 (163 response and 138 nonresponse) was used to train, validate, and test the DMIL model and dataset 2 (22 response and 20 nonresponse) was used as the external validation cohort. Five backbone networks in the feature extraction module and three pooling methods were compared. The DMIL with a pre-trained VGG16 backbone and an attention mechanism pooling performed the best, with an accuracy of 0.883 and area under the curve (AUC) of 0.982 on Dataset 1. While using max pooling and convolutional pooling, the AUC was 0.958 and 0.931, respectively. In Dataset 2, the best DMIL model produced an accuracy of 0.833 and AUC of 0.940. Deep learning models based on the MIL can predict chemotherapy response in NSCLC using pretreatment CT images and the pre-trained VGG16 with attention mechanism pooling yielded better predictions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Área Sob a Curva , Tomografia Computadorizada por Raios X/métodos
8.
Environ Technol ; : 1-30, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36420739

RESUMO

Currently, ofloxacin (OFX) is widely used in various medical treatment and aquaculture industries. However, its production and application produces waste which pollutes the natural environment and causes ecological damage. The application of biochar is a crucial way to remove OFX antibiotics from wastewater. In this paper, bagasse was used as the material to be pyrolyzed to obtain bagasse biochar (BC). BC was modified with HNO3 and KOH to prepare acid-modified sugarcane biochar (HBC) and alkali-modified sugarcane biochar and subsequently applied to the treatment of ofloxacin wastewater. The results showed that the adsorption capacity of HBC was 2.2 times higher than that of BC, and it had better adsorption performance. When the dosage of acid-modified biochar was 1 g/L and the initial pH of the solution was 7.0, the OFX removal rate reached 88.5% after 90 min of reaction. HBC has good stability, and the OFX removal efficiency is still up to 78.5% after 5 cycles. According to the adsorption simulation results, the adsorption of the three biochar materials is more consistent with the Freundlich adsorption model, and the simulated linear correlation coefficient is higher than 0.99. The Kfr value of HBC is 6.6042, which exhibits the highest adsorption capacity. Moreover, the three biochars exhibit better simulation results in pseudo-second-order kinetics fitting, and the linear correlation coefficients are above 0.99. The adsorption mechanism of bagasse biochar for ofloxacin in wastewater was π-π electron donor-acceptor interactions. The results show that bagasse biochar has good feasibility in the treatment of ofloxacin wastewater.

9.
Zhongguo Zhen Jiu ; 42(11): 1253-9, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36397223

RESUMO

OBJECTIVE: To observe the effect of five-element music therapy of traditional Chinese medicine (TCM) on the clinical symptoms and the quality of life in the patients with suboptimal health status (SHS) of liver stagnation and spleen deficiency and explore the corresponding specificity changes in the temperature of acupoints when zangfu functions are of dysfunction and recovered to be balanced, separately. METHODS: Sixty patients with SHS of liver stagnation and spleen deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, the conventional health education was provided. In the observation group, on the base of the therapeutic regimen as the control group, the patients received the five-element music therapy to pacify the liver qi and strengthen the spleen functions, once every two days, 30 min each time, 3 treatments a week. The course of treatment consisted of 4 weeks. Before and after treatment, the TCM syndrome score and the MOS 36-item short form healthy survey (SF-36) score were compared between the two groups and the clinical therapeutic effect was evaluated. Using infrared thermal imaging, the temperature at the acupoints of the affected organs (liver, spleen), the related organs (gallbladder, stomach) and the other non-related zangfu organs (pericardium, lung) was detected before and after treatment in the two groups. RESULTS: After treatment, the TCM syndrome scores were reduced when compared with those before treatment in the two groups (P<0.01, P<0.05); the reduction in the observation group was larger than that of the control group (P<0.01). The score of each domain for the SF-36 in the observation group and the score of role-emotional domain in the control group were all increased when compared with the scores before treatment (P<0.01, P<0.05); and the score of each domain for the SF-36 in the observation group was higher than that in the control group (P<0.01). The total effective rate was 66.7% (20/30) in the observation group, which was higher than 10.0% in the control group (3/30, P<0.05). In the observation group, the temperature of the yuan-primary point, the back-shu point and the front-mu point related to the liver, as well as those related to the gallbladder after treatment was reduced when compared with the temperature before treatment; and the changes were larger than those of the control group (P<0.01). The temperature of the yuan-primary point, the back-shu point and the front-mu point related to the spleen, as well as the back-shu point and the front-mu point related to the stomach in the observation group was increased when compared with the temperature before treatment (P<0.01); and the changes were larger than those of the control group (P<0.01). For the temperature of the non-specific points related to the liver and spleen, as well as the yuan-primary point, the back-shu point and the front-mu point related to the pericardium and the lung, there was no significant differences when compared with the temperature at the above-mentioned acupoints before and after treatment (P>0.05). CONCLUSION: TCM five-element music therapy associated with the conventional health education may effectively relieve the clinical symptoms and improve the quality of life in the patients with suboptimal health status of liver stagnation and sleep deficiency; and the therapeutic effect is better than the simple health education. The changes in the temperature of acupoints may reflect the functional regulation of the related zangfu organs in the body.


Assuntos
Pontos de Acupuntura , Musicoterapia , Humanos , Medicina Tradicional Chinesa , Baço , Qualidade de Vida , Temperatura , Fígado , Nível de Saúde
10.
Phys Med Biol ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322995

RESUMO

OBJECTIVE: Diabetic retinopathy (DR) grading is primarily performed by assessing fundus images. Many types of lesions, such as microaneurysms, hemorrhages, and soft exudates, are available simultaneously in a single image. However, their sizes may be small, making it difficult to differentiate adjacent DR grades even using deep convolutional neural networks (CNNs). Recently, a vision transformer (ViT) has shown comparable or even superior performance to CNNs, and it also learns different visual representations from CNNs. Inspired by this finding, we propose a two-path Contextual Transformer with Xception Network (CoT-XNet) to improve the accuracy of DR grading. APPROACH: The representations learned by CoT through one path and those by the Xception network through another path are concatenated before the fully connected layer. Meanwhile, the dedicated pre-processing, data resampling, and test time augmentation strategies are implemented. The performance of CoT-XNet is evaluated in the publicly available datasets of DDR, APTOS2019, and EyePACS, which include over 50,000 images. Ablation experiments and comprehensive comparisons with various state-of-the-art (SOTA) models have also been performed. MAIN RESULTS: Our proposed CoT-XNet shows better performance than available SOTA models, and the accuracy and Kappa are 83.10% and 0.8496, 84.18% and 0.9000, and 84.10% and 0.7684, respectively, in the three datasets (listed above). Class activation maps of CoT and Xception networks are different and complementary in most images. SIGNIFICANCE: By concatenating the different visual representations learned by CoT and Xception networks, CoT-XNet can accurately grade DR from fundus images and present good generalizability. CoT-XNet will promote the application of artificial intelligence-based systems in the DR screening of large-scale populations.

11.
Geroscience ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322234

RESUMO

The age-related decline in skeletal muscle mass and function is known as sarcopenia. Sarcopenia progresses based on complex processes involving protein dynamics, cell signaling, oxidative stress, and repair. We have previously found that 8-week treatment with elamipretide improves skeletal muscle function, reverses redox stress, and restores protein S-glutathionylation changes in aged female mice. This study tested whether 8-week treatment with elamipretide also affects global phosphorylation in skeletal muscle consistent with functional improvements and S-glutathionylation. Using female 6-7-month-old mice and 28-29-month-old mice, we found that phosphorylation changes did not relate to S-glutathionylation modifications, but that treatment with elamipretide did partially reverse age-related changes in protein phosphorylation in mouse skeletal muscle.

12.
Antioxidants (Basel) ; 11(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36421458

RESUMO

Protein S-glutathionylation (SSG) is a reversible post-translational modification (PTM) featuring the conjugation of glutathione to a protein cysteine thiol. SSG can alter protein structure, activity, subcellular localization, and interaction with small molecules and other proteins. Thus, it plays a critical role in redox signaling and regulation in various physiological activities and pathological events. In this review, we summarize current biochemical and analytical approaches for characterizing SSG at both the proteome level and at individual protein levels. To illustrate the mechanism underlying SSG-mediated redox regulation, we highlight recent examples of functional and structural consequences of SSG modifications. Finally, we discuss the analytical challenges in characterizing SSG and the thiol PTM landscape, future directions for understanding of the role of SSG in redox signaling and regulation and its interplay with other PTMs, and the potential role of computational approaches to accelerate functional discovery.

13.
Diagnostics (Basel) ; 12(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36428940

RESUMO

BACKGROUND: The occurrence and development of breast cancer has a strong correlation with a person's genetics. Therefore, it is important to analyze the genetic factors of breast cancer for future development of potential targeted therapies from the genetic level. METHODS: In this study, we complete an analysis of the relevant protein-protein interaction network relating to breast cancer. This includes three steps, which are breast cancer-relevant genes selection using mutual information method, protein-protein interaction network reconstruction based on the STRING database, and vital genes calculating by nodes centrality analysis. RESULTS: The 230 breast cancer-relevant genes were chosen in gene selection to reconstruct the protein-protein interaction network and some vital genes were calculated by node centrality analyses. Node centrality analyses conducted with the top 10 and top 20 values of each metric found 19 and 39 statistically vital genes, respectively. In order to prove the biological significance of these vital genes, we carried out the survival analysis and DNA methylation analysis, inquired about the prognosis in other cancer tissues and the RNA expression level in breast cancer. The results all proved the validity of the selected genes. CONCLUSIONS: These genes could provide a valuable reference in clinical treatment among breast cancer patients.

14.
Nutrients ; 14(22)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36432480

RESUMO

The recovery of the intestinal epithelial barrier is the goal for curing various intestinal injurious diseases, especially IBD. However, there are limited therapeutics for restoring intestinal epithelial barrier function in IBD. The stemness of intestinal stem cells (ISCs) can differentiate into various mature intestinal epithelial cells, thus playing a key role in the rapid regeneration of the intestinal epithelium. IL-22 secreted by CD4+ T cells and ILC3 cells was reported to maintain the stemness of ISCs. Our previous study found that L-fucose significantly ameliorated DSS-induced colonic inflammation and intestinal epithelial injury. In this study, we discovered enhanced ISC regeneration and increased intestinal IL-22 secretion and its related transcription factor AHR in colitis mice after L-fucose treatment. Further studies showed that L-fucose promoted IL-22 release from CD4+ T cells and intestinal lamina propria monocytes (LPMCs) via activation of nuclear AHR. The coculture system of LPMCs and intestinal organoids demonstrated that L-fucose stimulated the proliferation of ISCs through an indirect manner of IL-22 from LPMCs via the IL-22R-p-STAT3 pathway, and restored TNF-α-induced organoid damage via IL-22-IL-22R signaling. These results revealed that L-fucose helped to heal the epithelial barrier by accelerating ISC proliferation, probably through the AHR/IL-22 pathway of LPMCs, which provides a novel therapy for IBD in the clinic.

15.
Free Radic Biol Med ; 193(Pt 1): 373-384, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36306991

RESUMO

Perturbation to the redox state accompanies many diseases and its effects are viewed through oxidation of biomolecules, including proteins, lipids, and nucleic acids. The thiol groups of protein cysteine residues undergo an array of redox post-translational modifications (PTMs) that are important for regulation of protein and pathway function. To better understand what proteins are redox regulated following a perturbation, it is important to be able to comprehensively profile protein thiol oxidation at the proteome level. Herein, we report a deep redox proteome profiling workflow and demonstrate its application in measuring the changes in thiol oxidation along with global protein expression in skeletal muscle from mdx mice, a model of Duchenne Muscular Dystrophy (DMD). In-depth coverage of the thiol proteome was achieved with >18,000 Cys sites from 5,608 proteins in muscle being quantified. Compared to the control group, mdx mice exhibit markedly increased thiol oxidation, where a ∼2% shift in the median oxidation occupancy was observed. Pathway analysis for the redox data revealed that coagulation system and immune-related pathways were among the most susceptible to increased thiol oxidation in mdx mice, whereas protein abundance changes were more enriched in pathways associated with bioenergetics. This study illustrates the importance of deep redox profiling in gaining greater insight into oxidative stress regulation and pathways/processes that are perturbed in an oxidizing environment.

16.
Org Lett ; 24(40): 7334-7338, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36190803

RESUMO

In this work, we carried out computational studies to predict the cycloaddition efficiency of strained alkynes with 2H-pyran-2-one and its three sulfur-containing analogues: 2H-pyran-2-thione, 2H-thiopyran-2-one, and 2H-thiopyran-2-thione. It was predicted that the decreased aromaticity of the substrate would yield higher reactivity. Experimental studies confirmed the calculation results, and 2H-pyan-2-thiones were found to be the most reactive substrates. This reaction proceeded effectively in aqueous buffers and in cellular environments. It also produced COS as the byproduct, which could be converted into hydrogen sulfide (H2S) in the presence of carbonate anhydrase. This click-and-release approach may serve as a unique way to deliver COS/H2S to specific locations.


Assuntos
Sulfeto de Hidrogênio , Óxidos de Enxofre , Alcinos , Reação de Cicloadição , Piranos , Compostos de Sulfidrila , Enxofre , Tionas
17.
J Hematol Oncol ; 15(1): 143, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209184

RESUMO

The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future.


Assuntos
Antineoplásicos , Produtos Biológicos , Imunoconjugados , Neoplasias , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Imunoconjugados/uso terapêutico , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas , Tirosina , Estados Unidos , United States Food and Drug Administration
18.
Adv Mater ; : e2206101, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36269002

RESUMO

Assembling pristine graphene into freestanding films featuring high electrical conductivity, superior flexibility, and robust mechanical strength aims at meeting the all-around high criteria of new-generation electronics. However, voids and defects produced in the macroscopic assembly process of graphene nanosheets severely degrade the performance of graphene films, and mechanical brittleness often limits their applications in wide scenarios. To address such challenges, an electrostatic-repulsion aligning strategy is demonstrated to produce highly conductive, ultraflexible, and multifunctional graphene films. Typically, the high electronegativity of titania nanosheets (TiNS) induces the aligning of negatively charged graphene nanosheets via electrostatic repulsion in the film assembly. The resultant graphene films show fine microstructure, enhanced mechanical properties, and improved electrical conductivity up to 1.285 × 105 S m-1 . Moreover, the graphene films can withstand 5000 repeated folding without structural damage and electrical resistance fluctuation. These comprehensive improved properties, combined with the facile synthesis method and scalable production, make these graphene films a promising platform for electromagnetic interference (EMI) shielding and thermal-management applications in smart and wearable electronics.

19.
Cancer Sci ; 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36285479

RESUMO

Breast cancer is among the most common malignant cancers in women. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a transcriptional repressor that has been shown to be involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI-1 was found in both human triple negative breast cancer and luminal A-type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI-1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI-1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF-7/MDA-MB-231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC-209. Our results reveal that BMI-1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.

20.
Scand J Gastroenterol ; : 1-10, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36281578

RESUMO

OBJECTIVE: Little is known about association between the efficacy of probiotics and baseline gut microbiota in irritable bowel syndrome (IBS). We aimed to explore gut microbiota in diarrhea-predominant IBS (IBS-D) and whether baseline gut microbiota was related to the efficacy of Bacillus subtilis and Enterococcus faecium (BE). METHODS: This study recruited 19 healthy controls (HC) and 50 IBS-D patients, among whom 19 patients were administrated 500 mg BE orally three times daily for 2 weeks. Clinical data and fecal samples were collected from patients before and after treatment. 16S rRNA sequencing was performed to obtain fecal bacterial data. RESULTS: There was no significant difference of alpha diversity, beta diversity, profiles of microbial phyla and genera between HC and IBS. BE improved IBS-SSS (IBS severity scoring system) and stool consistency, and altered Enterococcus, Blautia, Lachnoclostridium and Fusobacterium without significant impact on microbial structure in IBS-D. Notably, baseline fecal bacterial composition differed between non-responders and responders to BE concerning abdominal pain and bloating, with Atopobium, Pyramidobacter, Ruminococcus gnavus and Peptostreptococcus enriched in responders in terms of abdominal pain. There was reduced abundance of Prevotella, Ruminococcaceae UCG, Eubacterium eligens, Faecalibacterium and Eubacterium coprostanoligenes in responders compared with non-responders. Furthermore, BE increased beneficial bacteria including Faecalibacterium, Blautia and Butyricicoccus, decreased Lachnoclostridium and Bilophila, and influenced some microbial metabolic pathways in responders, such as mineral absorption, metabolism of arachidonic acid, d-arginine, D-ornithine, phenylalanine and vitamin B6. CONCLUSION: Baseline fecal microbiome is associated with the efficacy of BE in attenuating abdominal pain and bloating in IBS-D.

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