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1.
Bioact Mater ; 21: 194-208, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36101856

RESUMO

Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell derived-small extracellular vesicles (sEVs) for tendinopathy has been validated in recent years. However, whether large extracellular vesicles (lEVs), another subset of extracellular vesicles, possesses the ability for the improvement of tendinopathy remains unknown. Here, we showed that lEVs secreted from iPSC-derived MSCs (iMSC-lEVs) significantly mitigated pain derived from tendinopathy in rats. Immunohistochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue. Meanwhile, in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs, and this effect was mediated by regulating p38 MAPK pathway. Moreover, liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs, including 134 new-found proteins beyond current Vesiclepedia database. By bioinformatics and Western blot analyses, we showed that DUSP2 and DUSP3, the negative regulator of p38 phosphorylation, were enriched in iMSC-lEVs and could be transported to macrophages. Further, the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients. Taken together, our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity, which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3, and might be a promising candidate for tendinopathy therapy.

2.
Small ; 18(12): e2106196, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322558

RESUMO

Cell mechanical forces play fundamental roles in regulating cellular responses to environmental stimulations. The shortcomings of conventional methods, including force resolution and cellular throughput, make them less accessible to mechanical heterogeneity at the single-cell level. Here, a DNA tensioner platform is introduced with high throughput (>10 000 cells per chip) and pN-level resolution. A microfluidic-based cell array is trapped on "hairpin-structured" DNA tensioners that enable transformation of the mechanical information of living cells into fluorescence signals. By using the platform, one can identify enhanced mechanical forces of drug-resistant cells as compared to their drug-sensitive counterparts, and mechanical differences between metastatic tumor cells in pleural effusion and nonmetastatic histiocytes. Further genetic analysis traces two genes, VEGFA and MINK1, that may play deterministic roles in regulating mechanical heterogeneities. In view of the ubiquity of cells' mechanical forces in the extracellular microenvironment (ECM), this platform shows wide potential to establish links of cellular mechanical heterogeneity to genetic heterogeneity.


Assuntos
DNA , Microfluídica
3.
Clin. transl. oncol. (Print) ; 24(10): 1954–1963, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207951

RESUMO

Purpose: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.MethodsThe biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.ResultsThrough bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.ConclusionsIn general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients. (AU)


Assuntos
Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica , Oncogenes , MicroRNAs , RNA Longo não Codificante
4.
Mater Today Bio ; 16: 100410, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36090609

RESUMO

As one of the main functions of vascular endothelial cells, Vascular permeability is determined by four tight junction proteins (TJPs): Zonula Occludens-1 (ZO-1), Claudin-5, Occludin and Tricellulin. The barrier function of blood vessels will be reconstructed after they are damaged by endothelial mechanical injuries caused by vascular interventions. In this study, the effects of balloon expansion (transient mechanical injury) on four TJPs and vascular permeability were compared with those of poly-l-lactic acid bioresorbable scaffolds (BRSs) implantation (continuous mechanical stimulation). We found that BRSs do not affect vascular permeability, while the recovery of vascular barrier function was found to be only related to the mechanical injuries and repair of endothelium. Mechanical stimulation affects and accelerates the recovery process of vascular permeability with the heterogeneous expression levels of TJPs induced after BRSs implantation. Different TJPs have different sensitivity to different loyal mechanical stimuli. ZO-1 is more sensitive to shear stress and tension than to static pressure. Occludin is sensitive to static pressure and shear stress. Tricellulin is more sensitive to tension stretching. Compared with the other three TJPs, Claudin-5 can respond to mechanical stimulation, with relatively low sensitivity, though. This difference in sensitivity determines the heterogeneous expression of TJPs. Mechanical stimulation of different kinds and strengths can also cause different cell morphological changes and inflammatory reactions. As an important element affecting endothelial function, the mechanical factors emerging after BRSs implantation are worthy of more attention.

5.
Sports Med Health Sci ; 4(3): 160-171, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36090918

RESUMO

A Chinese Compilation of Physical Activities was compiled to estimate the energy costs of physical activities (PAs) using data on adults aged 18-64. Data were obtained from published articles and laboratory measurements. Databases, including PubMed, Embase, Scopus, Ebsco, Web of Science, Chinese National Knowledge Infrastructure, Wan Fang Data, National Science and Technology Report Service, Public Health Scientific Data were searched to collect data from inception to January 2022, on energy expenditure associated with PA in the healthy Chinese population. Two reviewers independently screened the literature and extracted, classified, and summarized data. Data were measured for 36 PAs using indirect calorimetry. Detailed descriptions of specific activities and metabolic equivalent values were provided by summarizing 241 physical activities in 13 categories. The first edition of the Chinese Compilation of PAs in Healthy Adults Aged 18-64(CCPA) was created. It provides valuable resources for people who regularly engage in physical exercise, researchers, educators, fitness professionals, and health or commercial sectors to quickly obtain various PA MET intensities. In the future, the energy expenditure of various PAs of different ages within the Chinese population can be measured based on the CCPA.

6.
Front Nutr ; 9: 967902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091250

RESUMO

Backgrounds: The patient-generated subjective global assessment (PG-SGA) is one of the screening criteria for malnutrition, the skeletal muscle radiodensity (SMD) and skeletal muscle mass index (SMI) are associated with survival in colorectal cancer patients. Body composition parameters can be easily assessed; however, few studies have examined the association between total muscle wasting scores in PG-SGA and body composition parameters and two muscle abnormalities. Methods: This cohort study included 1,637 stage I-III CRC patients from 2 clinical centers in China, who were enrolled in the training cohort (n = 1,005) and validation cohort (n = 632). Baseline data were collected prospectively from patients including age, BMI, staging, gait speed, hand grip strength (HGS), peak expiratory flow (PEF), neutrophil-lymphocyte ratio (NLR), intermuscular adipose tissue (IMAT), visceral fat area (VFA) and total muscle wasting score in PG-SGA. Relevant risk factors were subjected to logistic regression analysis and Cox regression analysis to identify characteristics associated with muscle abnormalities and survival. Based on the logistic model results, normograms were established to predict muscle abnormalities, and its discrimination and calibration were assessed using the receiver operating characteristic (ROC) curve and calibration curve. The Kaplan-Meier curves were used to assess the survival of colorectal cancer patients with malnutrition or sarcopenia in an inflammatory state (assessed by NLR). Results: The mean age of all participants was 57.7 ± 10.6 years (56.9% males) and the prevalence of low SMD and low SMI was 32.2 and 39.5%, respectively. Low SMD rate was significantly associated with age, TNM stage, BMI, IMAT, walking speed, total muscle wasting score and NRS2002 score by logistic regression analysis (p < 0.05). Low SMI rate was significantly correlated with age, NLR, BMI, PEF, handgrip strength, calf circumference, walking speed, total muscle wasting score and NRS2002 score (p < 0.05). The AUCs of the diagnostic nomograms were 0.859 (95% CI, 0.831-0.886) for low SMD and 0.843 (95% CI, 0.813-0.871) for low SMI in the validation cohort. We also found that patients with colorectal cancer with malnutrition or sarcopenia had a worse prognosis when NLR ≥3.5. Conclusion: Muscle abnormalities and malnutrition are strongly associated with mortality in patients with non-metastatic colorectal cancer. Early identification and intervention of the associated risk factors may offer new ways to improve patient prognosis.

7.
Front Pharmacol ; 13: 955905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091783

RESUMO

Herbs with a "hot" properties are frequently used to treat cold symptoms in TCM. However, the underlying mechanisms of the herbs with "hot" properties on hypothyroidism have not been investigated. This study aimed to explore four typical "hot" and "cold" property herb on hypothyroidism. Firstly, the difference efficacy between the four typical "hot" property herbs and the four typical "cold" property herbs was assessed by physical signs, thyroid function, and the metabolic profile using multivariate statistical analysis. The influence of the four typical "hot" property herbs on hypothyroidism was validated pathologically. The impact mechanism of the four typical "hot" property herbs on hypothyroidism was investigated through a metabolomics method combined with network analysis. Na+/K+-ATP, ACC1 enzyme, UCP-1, and the PI3K-Akt pathway were used to confirm the metabolite pathways and target-associated metabolites. The results showed that the four typical "hot" property herbs could significantly improve physical signs, thyroid function, and the metabolic profile in hypothyroidism rats, the four typical "cold" property herbs did not show any benefit. Moreover, the four typical "hot" property herbs could improve lipid metabolism, energy metabolism, and thyroid hormone levels by the PI3K-Akt signaling pathway, Ca2+- AMPK signaling pathways, purine metabolism, and tryptophan metabolism. Additionally, the levels of UCP-1, Na+/K + -ATP enzyme, and ACC1 were ameliorated by the four typical "hot" property herbs in hypothyroidism rats. Therefore, a metabolomics strategy combined with network analysis was successfully performed and interpreted the mechanism of the four typical "hot" property herbs on hypothyroidism based on the theory of "cold and hot" properties of TCM well.

8.
Transl Androl Urol ; 11(8): 1083-1095, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092839

RESUMO

Background: In recent years, a large number of clinical and epidemiological studies have revealed the anti-cancer activity of propranolol in solid tumors, though the underline mechanism is yet to be clarified. Methods: The proliferation of bladder cancer cells treated with propranolol was detected by MTS assays. In vivo tumor xenograft experiments were used to observe the effect of propranolol on bladder cancer growth in mice. The expression levels of Na+/H+ exchanger (NHE1) was measured by western blot. The frequency of CD8+ T cells and CD4+ T cells were detected via flow cytometry. Results: In this study, propranolol inhibited the expression of NHE1 and sequentially led to a decrease of intracellular pH to 5.88 in MB49 cells and 6.85 in 5637 cells, thereafter, inhibited cell viability and induced apoptosis. Furthermore, propranolol inhibited the growth of bladder cancer in mice xenograft model. Flow cytometry found that the frequency of CD8+ T cells (34.58±2.11 vs. 32.34±0.6, P=0.35) and CD4+ T cells (57.80±2.45 vs. 51.44±0.79, P=0.06) in the spleen did not change compared with the control group, while the expression of IFN-γ, GZMB and T-bet secreted by CD8+ T cells increased respectively (IFN-γ 7.3±0.17 vs. 3.37±0.58, P=0.0017; GZMB 16.66±2.13 vs. 4.53±0.62, P=0.0034; T-bet 3.62±0.35 vs. 1.74±0.26, P=0.0027). Meantime, the expression of FoxP3 on CD4+ T cells decreased both in spleen and tumor tissue (1.53±0.11 vs. 0.91±0.1, P=0.004; 4.52±0.48 vs. 1.76±0.40, P=0.003). Conclusions: These results suggested that propranolol exerted anti-proliferation and pro-apoptosis effects in bladder cancer cell by inhibiting Na+/H+ exchange and activated systemic anti-tumor immune response in vivo.

9.
Nanoscale Horiz ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097878

RESUMO

Due to the elusive structure-function relationship, traditional nanocatalysts always yield limited catalytic activity and selectivity, making them practically difficult to replace natural enzymes in wide industrial and biomedical applications. Accordingly, single-atom catalysts (SACs), defined as catalysts containing atomically dispersed active sites on a support material, strikingly show the highest atomic utilization and drastically boosted catalytic performances to functionally mimic or even outperform natural enzymes. The molecular characteristics of SACs (e.g., unique metal-support interactions and precisely located metal sites), especially single-atom iron catalysts (Fe-SACs) that have a similar catalytic structure to the catalytically active center of metalloprotease, enable the accurate identification of active centers in catalytic reactions, which afford ample opportunity for unraveling the structure-function relationship of Fe-SACs. In this review, we present an overview of the recent advances of support materials for anchoring an atomic dispersion of Fe. Subsequently, we highlight the structural designability of support materials as two sides of the same coin. Moreover, the applications described herein illustrate the utility of Fe-SACs in a broad scope of industrially and biologically important reactions. Finally, we present an outlook of the major challenges and opportunities remaining for the successful combination of single Fe atoms and catalysts.

10.
Neurochem Res ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098889

RESUMO

Short-chain fatty acids (SCFAs) are known to be actively involved in neurological diseases, but their roles in hypoxic-ischaemic brain injury (HIBI) are unclear. In this study, a rat model of HIBI was established, and this study measured the changes in IL-6 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), in addition to proliferation and apoptosis indicators of oligodendrocyte precursor cells (OPCs). The mechanism of action of SCFA on astrocytes was also investigated. Astrocytes were subjected to hypoxia in vitro, and OPCs were treated with IL-6. The results showed that SCFAs significantly alleviated HIBI-induced activation of astrocytes and loss of OPCs. SCFA pretreatment (1) downregulated the expression of NLRP3, IL-6, CCL2, and IP-10; (2) had no effect on the proliferation of OPCs; (3) ameliorated the abnormal expression of Bax and Bcl-2; and (4) regulated IL-6 expression via the SGK1-related pathway in astrocytes. Our findings revealed that SCFAs alleviated the loss of OPCs by regulating astrocyte activation through the SGK1/IL-6 signalling pathway.

11.
J Control Release ; 350: 898-921, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36089171

RESUMO

Advanced drug delivery systems are of vital importance to enhance therapeutic efficacy. Among various recently developed formulations, self-assembling hydrogels composed of therapeutic agents have shown promising potential for local drug delivery owing to their excellent biocompatibility, high drug-loading efficiency, low systemic toxicity, and sustained drug release behavior. In particular, therapeutic agents self-assembling hydrogels with well-defined nanostructures are beneficial for direct delivery to the target site via injection, not only improving drug availability, but also extending their retention time and promoting cellular uptake. In brief, the self-assembly approach offers better opportunities to improve the precision of pharmaceutical treatment and achieve superior treatment efficacies. In this review, we intend to cover the recent developments in therapeutic agent self-assembling hydrogels. First, the molecular structures, self-assembly mechanisms, and application of self-assembling hydrogels are systematically outlined. Then, we summarize the various self-assembly strategies, including the single therapeutic agent, metal-coordination, enzyme-instruction, and co-assembly of multiple therapeutic agents. Finally, the potential challenges and future perspectives are discussed. We hope that this review will provide useful insights into the design and preparation of therapeutic agent self-assembling hydrogels.

12.
Chin Med ; 17(1): 110, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36109779

RESUMO

BACKGROUND: Bi Zhong Xiao decoction (BZXD), a traditional Chinese herbal formula, has been used clinically for many years to treat rheumatoid arthritis (RA). Both clinical and experimental studies have revealed that BZXD is effective in treating RA, but the mechanism remains unclear. In this study, we aimed to explore the mechanism of efficacy of BZXD through transcriptomic analysis of lncRNA and mRNA. METHODS: The combination method of ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry was used to assess the quality of BZXD. The efficacy of BZXD in treating collagen-induced arthritis (CIA) was evaluated by clinical assessment, weight changes, hematoxylin-eosin and safranin o-fast green staining, and Micro-CT. Arraystar rat lncRNA-mRNA chip technology was used to determine the lncRNA and mRNA expression profiles of the Control, CIA and BZXD groups, and to screen gene expression profiles related to the curative effect of BZXD. A lncRNA-mRNA co-expression network was constructed for the therapeutic efficacy genes. Through GO function and KEGG pathway enrichment analysis, the biological functions and signaling pathways of therapeutic efficacy genes were determined. Based on fold change and functional annotation, key differentially expressed lncRNAs and mRNAs were selected for reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. The functions of lncRNAs targeting mRNAs were verified in vitro. RESULTS: We demonstrated that BZXD could effectively reverse bone erosion. After BZXD treatment, up to 33 lncRNAs and 107 mRNAs differentially expressed genes were reversely regulated by BZXD. These differentially expressed lncRNAs are mainly involved in the biological process of the immune response and are closely related to the ECM-receptor interaction, MAPK signaling pathway, Focal adhesion, Ras signaling pathway, Antigen processing and presentation, and Chemokine signaling pathway. We identified four lncRNAs (uc.361-, ENSRNOT00000092834, ENSRNOT00000089244, ENSRNOT00000084631) and three mRNAs (Acvr2a, Cbx2, Morc4) as potential therapeutic targets for BZXD and their microarray data consistent with the RT-qPCR. In vitro experiments confirmed that silencing the lncRNAs ENSRNOT00000092834 and ENSRNOT00000084631 reversed the expression of target mRNAs. CONCLUSIONS: This study elucidates the possible mechanism of BZXD reversing bone erosion in CIA rats from the perspective of lncRNA and mRNA. To provide a basis and direction for further exploration of the mechanism of BZXD in treating RA.

13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(9): 1172-1177, 2022 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-36111482

RESUMO

Objective: To summarize the evaluation methods of postoperative healing of supraspinatus tendon tear in recent years, in order to provide reference for clinic. Methods: CNKI, Wanfang, PubMed, and Foreign Medical Literature Retrieval Service (FMRS) databases were used to search the literatures between 2005 and 2022. The literature related to the diagnosis and postoperative healing of supraspinatus tendon tear was included. Finally, 50 articles were reviewed. Results: Supraspinatus tendon tear is a common shoulder disease. Physical examination, clinical score, and imaging examination are used to predict and evaluate the postoperative healing. Among them, physical examination and clinical score are non-invasive and the most economical methods, but their accuracy and sensitivity are lower than imaging examination, so they can only be used as auxiliary methods. The acromio-humeral distance (AHD) and upward migration index (UMI) measured by X-ray films can directly reflect the change of supraspinatus tendon thickness, but they are impossible to distinguish whether there is tear or not. Ultrasound and MRI are the main methods for the clinical diagnosis of supraspinatus tendon tear, but the commonly used MRI sequence can not accurately judge the internal healing of the tendon. Shear wave elastrography (SWE) and ultrashort-echo-time (UTE) techniques are the latest research directions in recent years, but different studies have shown opposite conclusions on the application of SWE technique. This conclusion shows that the principle of SWE technique and its relationship with tendons need to be further studied. UTE technique has good clinical effect, and the T2* value obtained by UTE technique is more accurate than that of traditional Sugaya typing, but there are still few research samples. Conclusion: AHD and UMI measured by X-ray film and T2* value measured by UTE technique can be used as effective methods for evaluating the healing of supraspinatus tendon tear after repairing, and can be used as a follow-up evaluation method combined with physical examination and clinical score for patients with supraspinatus tendon tear.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Humanos , Úmero , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Ruptura/cirurgia , Tendões
14.
J Dig Dis ; 23(7): 396-403, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36111615

RESUMO

OBJECTIVE: We aimed to investigate the immunophenotype, differential diagnosis, and clinicopathological characteristics of signet-ring cell carcinoma (SRCC) derived from gastric foveolar epithelium. METHODS: Clinical characteristics, endoscopic findings, histopathological features, and follow-up data of seven cases of SRCC derived from gastric foveolar epithelium with small intramucosal lesions were analyzed. RESULTS: Seven patients with a mean age of 38.3 years were diagnosed with SRCC derived from gastric foveolar epithelium and small intramucosal lesions, all of them were negative for CDH-1 germline mutation. The glands proliferated and expanded, and then morphologically transformed into signet-ring cells and formed clonal hyperplastic SRCC, which expanded laterally along the gastric foveolar cells to a length of 3-6 mm. Periodic acid Schiff staining was positive, while CK7 and MUC6 were negative, in all cases. Ki-67-positive cells ranged 37%-60%. During a follow-up period of 6-30 months, no patients experienced tumor recurrence or metastasis. CONCLUSIONS: SRCC derived from gastric foveolar epithelium is originated from the proliferative region of the bottom of the gastric pit and gland neck. It is easily missed diagnosed or misdiagnosed as it grows laterally along the gastric foveolar cells. Biological behavior, genetics, and etiology of such SRCC, as well as the clinicopathological characteristics, need to be further studied.


Assuntos
Carcinoma de Células em Anel de Sinete , Recidiva Local de Neoplasia , Pólipos Adenomatosos , Adulto , Carcinoma de Células em Anel de Sinete/patologia , Epitélio/patologia , Humanos , Antígeno Ki-67 , Ácido Periódico , Neoplasias Gástricas
15.
Cancer Lett ; : 215919, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36116741

RESUMO

In cancer cells, poly(ADP-ribose) polymerase (PARP)-1 and PARP2 initiate and regulate DNA repair pathways to protect against DNA damage and cell death caused by radiotherapy or chemotherapy. Radiotherapy and PARP inhibitors (PARPis) have been combined in clinical trials, but their action mechanisms remain unclear. Here, we show that activated by ionizing radiation (IR) generated dsDNA, cyclic GMP-AMP synthase (cGAS) signaling promoted regulated cell death, specifically ferroptosis, via the activating transcription factor 3 (ATF3)-solute carrier family 7 member 11 axis and the antitumor immune response via the interferon-ß-CD8+ T cell pathway. Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS knockdown (KD) compromised IR-induced ferroptosis via downregulation of ATF3 (key ferroptosis regulator) expression. cGAS depletion reversed IR-induced infiltration of CD8+ T or CD8+GZMB+ T cells in the cGAS KD group. Survival analysis of paired tumor samples before and after standard radiotherapy revealed that high expression levels of cGAS, ATF3, and PTGS2 and high density of CD8+ T cells resulted in a significantly high disease-free survival rate in patients with rectal cancer. Therefore, PARPi treatment increases the cytoplasmic accumulation of dsDNA caused by IR, triggering the cGAS signaling-mediated tumor control in cancer cell lines and mouse xenograft models.

16.
Health Inf Sci Syst ; 10(1): 29, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36124094

RESUMO

Purpose: Abnormal phosphorylation has been proved to associate with a variety of human diseases, and the identification of phosphorylation sites is one of the research hotspots in healthcare. The study of phosphorylation site prediction in deep learning models often introduces a variety of information, and the utilization of complex models limits the usage scenarios of the models. Methods: An enhanced deep learning method with S-padding strategy based on convolutional neural network is proposed in this paper. The S-padding strategy forms a three-dimensional matrix with extension information from original amino acid sequences, and a corresponding 2D-CNN model is designed to abstract the comprehensive features of phosphorylation site area in protein sequences. Results: The fivefold cross-validation experiments are conducted, and the results show the performance of the proposed method on human dataset can achieve an accuracy of 89.68 % on serine/threonine sites and 88.16 % on tyrosine sites, respectively. Furthermore, phosphorylation site prediction on different organisms obtains the accuracy, sensitivity, and specificity of over 0.85, indicating a potential capability on phosphorylation site prediction task. Comparison result with existing models shows that the proposed method obtains better performance on both accuracy and AUC value, and the proposed method can further improve performance with sufficient training data. Conclusion: This method enables proteome-wide predictions via models trained on a large amount of phosphorylation data, further exploiting the potential of protein phosphorylation site identification, and helping to provide insights into phosphorylation mechanisms.

17.
Neurosurgery ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129281

RESUMO

BACKGROUND: In-stent stenosis (ISS) is a delayed complication that can occur after pipeline embolization device use when treating intracranial aneurysms (IAs). OBJECTIVE: To assess the incidence, predictors, and outcomes of ISS. METHODS: This was a retrospective, multicenter, observational study. All patient data were collected from a PLUS registry study. We collected data from patients with IA who completed digital subtraction angiography at follow-up and divided patients into "non-ISS," "mild ISS," or "severe ISS" groups. Multivariate logistic regression analysis was conducted to determine predictors of ISS. RESULTS: A total of 1171 consecutive patients with 1322 IAs participated in this study. Angiographic follow-up was available for 662 patients with 728 IAs, and the mean follow-up time was 9 months. ISS was detected in 73 cases (10.03%), including 61 mild ISS cases and 12 severe ISS cases. Univariate and multivariable analysis demonstrated that current smoking history (mild ISS: OR 2.15, 95% CI 1.122-4.118, P = .021; severe ISS: OR 5.858, 95% CI 1.186-28.93, P = .030) and cerebral atherosclerosis (mild ISS: OR 5.694, 95% CI 3.193-10.15, P = .001; severe ISS: OR 6.103, 95% CI 1.384-26.91, P = .017) were independent predictors of ISS. Compared with the other groups, the severe ISS group had higher rate of ischemic stroke (33.3%). CONCLUSION: ISS occurs in approximately 10.03% of cases at a mean follow-up of 9 months. Statistically, current smoking history and cerebral atherosclerosis are the main predictors of ISS. Severe ISS may be associated with higher risk of neurological ischemic events in patients with IA after pipeline embolization device implantation.

18.
J Invest Dermatol ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122800

RESUMO

Multi-omic studies including RNA-Sequencing, single-cell RNA-Sequencing, and epigenomics can provide insight into the connection between anatomically heterogeneous gene expression profile of skin and dermatoses-predisposed sites, in which RNA-Sequencing is essential. Therefore, herein, 159 skin samples collected mainly from discarded normal skin tissue during surgical treatment for benign skin tumors were used for RNA-sequencing. Based on cluster analysis, the skin was divided into four regions, with each region showing specific physiological characteristics via differentially expressed gene analysis. The results showed that the head and neck region, perineum, and palmoplantar area were closely associated with lipid metabolism, hormone metabolism, and blood circulation and related neural regulation, respectively. Transcription factor enrichment indicated that different regions were associated with the development of adjacent tissues. Specifically, the head and neck region, trunk and extremities, perineum, and palmoplantar area were associated with the central nervous, axial, urogenital, and vascular systems, respectively. The results were imported into an open website (https://dermvis.github.io/) for retrieval. Our transcriptomic data elucidated that human skin exhibits transcriptomic heterogeneity reflecting physiological and developmental variation at different anatomic sites and provided guidance for further studies on skin development and dermatoses predisposed sites.

19.
STAR Protoc ; 3(3): 101650, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36065291

RESUMO

Syntheses using classic coupling reactions can be tedious, leading to a dearth of ambipolar semiconducting polymers. Here, we detail the rapid synthesis of balanced ambipolar polymers by using a carbon-hydrogen (C-H) activation strategy. Using this protocol, two C-H reactive hydrogenated monomers and six ambipolar polymers can be rapidly synthesized within 2 h via C-H activation and the optoelectronic properties of the resultant polymers can be characterized. We also describe the fabrication process and performance evaluation of the ambipolar polymers-based organic transistors. For complete details on the use and execution of this protocol, please refer to Shen et al. (2022).


Assuntos
Polímeros , Transistores Eletrônicos , Carbono , Hidrogênio
20.
Front Chem ; 10: 980173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118325

RESUMO

Photoluminescence materials have been widely applied in biological imaging and sensing, anti-counterfeiting, light-emitting diodes, logic gates et al. The fabrication of luminescent materials with adjustable emission color by self-assembly of π-conjugated molecules has attracted particular attention. In this study, we designed and synthesized a thiophene-based α-cyanostyrene-derivative (TPPA), then investigate its self-assembly morphology and fluorescence emission under different organic solvents, different proportions of H2O/THF (DMSO) mixture and different pH conditions by UV, FL and SEM images. It was found that TPPA formed nanoparticles by self-assembly in organic solvent (THF or DMSO), accompanied by strong fluorescence emission. However, with the increase of water ratio, the fluorescence intensity decreased accompany with red shift, and the self-assembly morphology changed from nanoparticles to fibers. More interestingly, when pillar[5]arene (P5) was added to form host-guest complex with TPPA, white light emission could be successfully constructed when the ratio of TPPA to P5 was 1:20 and THF to water was 19:1.

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