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1.
Cartilage ; : 19476035211049556, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636646

RESUMO

OBJECTIVE: A major obstacle in the clinical translation of engineered auricular scaffolds is the significant contraction and loss of topography that occur during maturation of the soft collagen-chondrocyte matrix into elastic cartilage. We hypothesized that 3-dimensional-printed, biocompatible scaffolds would "protect" maturing hydrogel constructs from contraction and loss of topography. DESIGN: External disc-shaped and "ridged" scaffolds were designed and 3D-printed using polylactic acid (PLA). Acellular type I collagen constructs were cultured in vitro for up to 3 months. Collagen constructs seeded with bovine auricular chondrocytes (BAuCs) were prepared in 3 groups and implanted subcutaneously in vivo for 3 months: preformed discs with ("Scaffolded/S") or without ("Naked/N") an external scaffold and discs that were formed within an external scaffold via injection molding ("Injection Molded/SInj"). RESULTS: The presence of an external scaffold or use of injection molding methodology did not affect the acellular construct volume or base area loss. In vivo, the presence of an external scaffold significantly improved preservation of volume and base area at 3 months compared to the naked group (P < 0.05). Construct contraction was mitigated even further in the injection molded group, and topography of the ridged constructs was maintained with greater fidelity (P < 0.05). Histology verified the development of mature auricular cartilage in the constructs within external scaffolds after 3 months. CONCLUSION: Custom-designed, 3D-printed, biocompatible external scaffolds significantly mitigate BAuC-seeded construct contraction and maintain complex topography. Further refinement and scaling of this approach in conjunction with construct fabrication utilizing injection molding may aid in the development of full-scale auricular scaffolds.

2.
Sci China Life Sci ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34668131

RESUMO

Diabetic cardiomyopathy (DCM) is a common complication in diabetic patients. The molecular mechanisms of DCM remain to be fully elucidated. The intronic long noncoding RNA of DACH1 (lncDACH1) has been demonstrated to be closely associated with heart failure and cardiac regeneration. In this study, we investigated the role of lncDACH1 in DCM and the underlying molecular mechanisms. The expression of lncDACH1 was increased in DCM hearts and in high glucose-treated cardiomyocytes. Knockout of lncDACH1 reduced mitochondrial oxidative stress, cell apoptosis, cardiac fibrosis and hypertrophy, and improved cardiac function in DCM mice. Overexpression of lncDACH1 exacerbated mitochondria-derived reactive oxygen species (ROS) level and apoptosis, decreased activity of manganese superoxide dismutase (Mn-SOD); while silencing of lncDACH1 attenuated ROS production, mitochondrial dysfunction, cell apoptosis, and increased the activity of Mn-SOD in cardiomyocytes treated with high glucose. LncDACH1 directly bound to sirtuin3 (SIRT3) and facilitated its degradation by ubiquitination, therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse hearts. In addition, SIRT3 silencing abrogated the protective effects of lncDACH1 deficiency in cardiomyocytes. In summary, lncDACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse hearts. Inhibition of lncDACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy.

3.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2722-2728, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664444

RESUMO

Pure and mixed larch (Larix pricipis-rupprechtii) and birch (Betula platyphylla) plantations in Saihanba area were selected as test objects, with two stand density (200-340 and 880-1100 trees·hm-2) of each stand type. Based on tree size-stratified sampling approach, a total of 668 tree core samples were collected. A linear mixed model was used to analyze the effects of tree species interaction, stand density, and tree size on larch productivity. Results showed that basal area increment of larch was affected by competition, diameter at breast height, tree age, and neighborhood density to different degrees. Overyielding of larch was mainly due to the positive effect of birch on larch growth in the mixed plantation with higher stand density. For mixed plantation with lower stand density, the productivity of those two species was lower than that pure plantation because of a lack of species interaction. Intraspecific competition was the main factor influencing larch productivity. Larch productivity was positively affected by tree size, with the magnitude of tree size effect varying with stand density and species composition. Suitable enhancement of stand density and selection of birch as the mixing tree species could improve productivity of larch.

4.
Acta Pharmacol Sin ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493812

RESUMO

Myocardial ischemia-reperfusion (I/R) injury is a pathological process characterized by cardiomyocyte apoptosis, which leads to cardiac dysfunction. Increasing evidence shows that abnormal expression of long noncoding RNAs (lncRNAs) plays a crucial role in cardiovascular diseases. In this study we investigated the role of lncRNAs in myocardial I/R injury. Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h. We showed that lncRNA KnowTID_00006395, termed lncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H2O2-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overexpression of lncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs, whereas knockdown of lncRNA-6395 attenuated H2O2-induced cell apoptosis. LncRNA-6395 knockout mice (lncRNA-6395+/-) displayed improved cardiac function, decreased plasma LDH activity and infarct size following I/R injury. We demonstrated that lncRNA-6395 directly bound to p53, and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus. More importantly, overexpression of p53 canceled the inhibitory effects of lncRNA-6395 knockdown on cardiomyocyte apoptosis, whereas knockdown of p53 counteracted the apoptotic effects of lncRNA-6395 in cardiomyocytes. Taken together, lncRNA-6395 as an endogenous pro-apoptotic factor, regulates cardiomyocyte apoptosis and myocardial I/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.

5.
Nutrients ; 13(9)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34578965

RESUMO

BACKGROUND: As life expectancy increases, cognitive performance decline in the elderly has become one of the major global challenges. We aimed to evaluate the association of dietary vitamin D (VD), serum 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2), and total 25-hydroxyvitamin (25(OH)D) concentration with cognitive performance in older Americans. METHODS: The data from the National Health and Nutrition Examination Survey (NHANES), 2011-2014 was used. The cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). A binary logistic regression model was applied to evaluate the association between VD and cognitive performance, and restricted cubic spline model was adopted to evaluate the dose-response relationship. RESULTS: While comparing to the lowest dietary VD intake group, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest dietary VD intake group were 0.51 (0.36-0.72) for the Animal Fluency test score and 0.45 (0.31-0.66) for DSST score, respectively; and those of serum total 25(OH)D and 25(OH)D3 concentration were 0.68 (0.47-0.97) and 0.62 (0.44-0.86) for DSST score. L-shaped relationships were identified for dietary VD intake, serum total 25(OH)D and 25(OH)D3 concentration with cognition performance. The associations between dietary VD intake, serum total 25(OH)D and cognitive performance were non-significant when stratified by gender. CONCLUSIONS: The study indicates that dietary VD intake, serum total 25(OH)D and 25(OH)D3 concentration were positively associated with cognitive performance. Further studies are needed to clarify the possible effects of dietary VD intake and serum 25(OH)D2, 25(OH)D3 on cognitive performance.

6.
J Immunol ; 207(8): 2039-2050, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34535574

RESUMO

Thymic epithelial cells (TECs) are critical for the development and generation of functionally competent T cells. Until now, the mechanism that regulates the survival of TECs is poorly understood. In the current study, we found that Tsc1 controls the homeostasis of medullary TECs (mTECs) by inhibiting lysosomal-mediated apoptosis pathway in mice. TEC-specific deletion of Tsc1 predominately decreased the cell number of mTECs and, to a lesser content, affected the development cortical TECs. The defect of mTECs caused by Tsc1 deficiency in mice impaired thymocyte development and peripheral T cell homeostasis. Mechanistically, Tsc1 deficiency did not affect the cell proliferation of mTECs but increased the apoptosis of mTECs significantly. RNA-sequencing analysis showed that pathways involved in lysosomal biogenesis, cell metabolism, and apoptosis were remarkably elevated in Tsc1-deficient mTECs compared with their wild-type counterparts. Tsc1-deficient mTECs exhibited overproduction of reactive oxygen species and malfunction of lysosome, with lysosome membrane permeabilization and the release of cathepsin B and cathepsin L to the cytosol, which then lead to Bid cleaved into active truncated Bid and subsequently intrinsic apoptosis. Finally, we showed that the impaired development of mTECs could be partially reversed by decreasing mTORC1 activity via haploinsufficiency of Raptor Thus, Tsc1 is essential for the homeostasis of mTECs by inhibiting lysosomal-mediated apoptosis through mTORC1-dependent pathways.

7.
Invest Ophthalmol Vis Sci ; 62(12): 26, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34554178

RESUMO

Purpose: To characterize vitreous microparticles (MPs) in patients with traumatic proliferative vitreoretinopathy (PVR) and investigate their role in PVR pathogenesis. Methods: Vitreous MPs were characterized in patients with traumatic PVR, patients with rhegmatogenous retinal detachment (RRD) complicated with PVR, and control subjects by flow cytometry. The presence of M2 macrophages in epiretinal membranes was measured by immunostaining. Vitreous cytokines were quantified by ELISA assay. For in vitro studies, MPs isolated from THP-1 cell differentiated M1 and M2 macrophages, termed M1-MPs and M2-MPs, were used. The effects and mechanisms of M1-MPs and M2-MPs on RPE cell proliferation, migration, and epithelial to mesenchymal transition were analyzed. Results: Vitreous MPs derived from photoreceptors, microglia, and macrophages were significantly increased in patients with traumatic PVR in comparison with control and patients with RRD (PVR), whereas no significance was identified between the two control groups. M2 macrophages were present in epiretinal membranes, and their signature cytokines were markedly elevated in the vitreous of patients with traumatic PVR. Moreover, MPs from M2 macrophages were increased in the vitreous of patients with traumatic PVR. In vitro analyses showed that M2-MPs promoted the proliferation and migration of RPE cells via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. However, M2-MPs did not induce the expression of fibrotic proteins, including fibronectin, α-smooth muscle actin, and N-cadherin in RPE cells. Conclusions: This study demonstrated increased MP shedding in the vitreous of patients with traumatic PVR; specifically, MPs derived from M2 polarized macrophages may contribute to PVR progression by stimulating RPE cell proliferation and migration.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34481986

RESUMO

OBJECTIVE: To compare the rate of postoperative urinary retention and time to discharge between bladder backfilling and standard catheter removal for trial of void (TOV) after outpatient laparoscopic gynecologic surgery. Our secondary objectives were to compare the time to void, postoperative complications, and patient satisfaction. DATA SOURCES: We searched the PubMed, Ovid MEDLINE, Embase, Cochrane Library databases, and relevant reference lists of eligible articles up to March of 2021. METHODS OF STUDY SELECTION: This review included randomized controlled trials (RCTs) of TOV after outpatient laparoscopic gynecologic surgery. Odds ratios (ORs) with 95% confidence interval (CI) and weighted mean differences (WMDs) were reported. The quality of the studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed with Review Manager 5.4 software (RevMan 5.4.1; Cochrane Collaboration, London, United Kingdom). TABULATION, INTEGRATION, AND RESULTS: Five RCTs (N = 488) were included. The bladder backfilling group had a significantly shorter time to void than the standard TOV group (WMD, -25.19 minutes; 95% CI, -44.60 to -5.77; p = .01). Successful TOV was not significantly different between the 2 (OR, 0.92; 95% CI, 0.51 to -1.65; p = .77), without significant heterogeneity (I2 = 24%). There was also no significant difference in the time to discharge between the 2 TOV techniques (WMD, -25.19 minutes; 95% CI, -44.60 to -5.77; p = .01). There was no significant difference in complication rates or patient satisfaction between the 2 groups. CONCLUSION: The bladder backfilling technique of TOV after outpatient laparoscopic gynecologic surgery may reduce the time to first spontaneous void without affecting patient satisfaction or postoperative complications, but it does not significantly affect the time to discharge or urinary retention.

9.
Int Immunopharmacol ; 99: 108015, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339962

RESUMO

Dioscin is a natural steroid saponin derived from plants of the genus Dioscoreaceae. Previous studies have proved its effects of antibacterial, anti-inflammatory and hypolipidemic. In this study, our aim was to explore the protective effect and preliminary mechanism of Dioscin on dextran sulfate sodium (DSS)-induced colitis in mice. The results showed that Dioscin reduced DSS-induced disease activity index (DAI) increase, colon length shortening and colon pathological damage. In addition, Dioscin reduced excessive inflammation by reversing the cytokines levels, reducing intestinal macrophage infiltration and promoting macrophage polarization to M2 phenotype. At the same time, Dioscin maintained the intestinal barrier function by increasing the expression of zonula occludens-1 (ZO-1), occludin and mucin (Muc)-2. Moreover, Dioscin inhibited NF-κB, MAPK signaling and nucleotide oligomerization domain-like receptor family pyrin domain ontaining 3(NLRP3) inflammasome pathway in DSS-induced colitis. These results suggest that Dioscin is a competent candidate for ulcerative colitis (UC) therapy in the future.

11.
Psychophysiology ; : e13920, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383329

RESUMO

Selective attention is essential when we face sensory inputs with distractions. In the past decades, Lavie's load theory of selective attention delineates a complete picture of distractor suppression under different attentional control load. The present study was originally designed to explore how reward modulates the load effect of attentional selection. Unexpectedly, it revealed new findings under extended attentional load that was not involved in previous work. Participants were asked to complete a rewarded attentive visual tracking task while presented with irrelevant auditory oddball stimuli, with their behavioral performance, event-related potentials and pupillary responses recorded. We found that although the behavioral performance and pupil sizes varied unidirectionally with the attentional load, the processing of distractors as reflected by the mismatch negativity (MMN) increased first and then decreased. In contrast to the prediction of Lavie's theory that attentional control fails to effectively suppress distractor processing under high attentional control load, our finding suggests that extremely high attentional control load may instead require suppression of distractor processing at a stage as early as possible. Besides, P3a, a positive-polarity response sometimes following the MMN, was not affected by the attentional load, but both N1 (a negative-polarity component peaking ~100 ms from sound onset) and P3a were weakened at higher reward, indicating that reward leads to attenuated early processing of distractor and thus suppresses the attentional orienting towards distractors. These findings altogether complement Lavie's load theory of selective attention, presenting a more complex picture of how attentional load and reward affects selective attention.

12.
BMC Urol ; 21(1): 107, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388999

RESUMO

BACKGROUND: To explore the risk factors for severe bleeding complications after percutaneous nephrolithotomy (PCNL) according to the modified Clavien scoring system. METHODS: We retrospectively analysed 2981 patients who received percutaneous nephrolithotomies from January 2014 to December 2020. Study inclusion criteria were PCNL and postoperative mild or severe renal haemorrhage in accordance with the modified Clavien scoring system. Mild bleeding complications included Clavien 2, while severe bleeding complications were greater than Clavien 3a. It has a good prognosis and is more likely to be underestimated and ignored in retrospective studies in bleeding complications classified by Clavien 1, so no analysis about these was conducted in this study. Clinical features, medical comorbidities and perioperative characteristics were analysed. Chi-square, independent t tests, Pearson's correlation, Fisher exact tests, Mann-Whitney and multivariate logistic regression were used as appropriate. RESULTS: Of the 2981 patients 70 (2.3%), met study inclusion criteria, consisting of 51 men and 19 women, 48 patients had severe bleeding complications. The remaining 22 patients had mild bleeding. Patients with postoperative severe bleeding complications were more likely to have no or slight degree of hydronephrosis and have no staghorn calculi on univariate analysis (p < 0.05). Staghorn calculi (OR, 95% CI, p value 0.218, 0.068-0.700, 0.010) and hydronephrosis (OR, 95% CI, p value 0.271, 0.083-0.887, 0.031) were independent predictors for severe bleeding via multivariate logistic regression analysis. Other factors, such as history of PCNL, multiple kidney stones, site of puncture calyx and mean corrected intraoperative haemoglobin drop were not related to postoperative severe bleedings. CONCLUSIONS: The absence of staghorn calculi and a no or mild hydronephrosis were related to an increased risk of post-percutaneous nephrolithotomy severe bleeding complications.

13.
J Ethnopharmacol ; 281: 114539, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34428522

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Clinical trials have demonstrated that Trametes robinophila Murr (Huaier granule) can inhibit recurrence and metastasis after hepatocellular carcinoma (HCC) resection, but its efficacy as an adjuvant therapy after thermal ablation of early HCC is unknown. AIM OF THE STUDY: To analyze the prognostic value and side effects of Huaier granules in HCC patients undergoing thermal ablation. MATERIALS AND METHODS: Clinical information from 340 eligible subjects with early-stage HCC who were admitted to our department from September 1, 2008 to January 1, 2019 was extracted from the electronic medical record database. They were divided into the thermal ablation + TCM group and the thermal ablation group. Differences in their overall survival (OS), progression-free survival (PFS), extrahepatic metastatic rate (EMR), and therapeutic side effects (TSEs) between the two groups were compared. Beneficiaries of the integrated treatment and adequate treatment length were predicted. RESULTS: The median follow-up was 32.5 months (range 2-122 months). The 1-year, 3-year and 5-year OS rates in the integrated treatment group and the control group were 93.2% vs. 92.6%, 54.5% vs. 51.4%, 23.5% vs. 19.7% (p = 0.110, HR 0.76(0.54-1.07)). The 1-year, 3-year and 5-year PFS rates were 78.8% vs. 69.4%, 50.6% vs. 40.6%, 35.3% vs. 26.5%, respectively (p = 0.020, HR 0.67(0.48-0.94)). The median OS (35 vs. 31 months) and PFS (24 vs. 12.5 months) were longer in the integrated treatment group. The EMR in the integrated treatment group was significantly lower than that in the control group (p = 0.018, HR 0.49 (0.27-0.89)). Patients with any two of the following three factors might be predicted to be beneficiaries of the integrated treatment, including younger than 65 years (p =0.039, HR 0.70 (0.50-0.98)), single tumor (p = 0.035, HR 0.70 (0.50-0.98), and tumor size ≤3 cm (p = 0.029, HR 0.69 (0.50-0.96). Patients with continuous oral administration of TCM following ablation had a lower probability of recurrence and metastasis within 2 years (p = 0.015, HR 0.67 (0.49-0.93)). Although the integrated treatment group reported a higher incidence of nausea and emesis, there were no significant differences between the two groups. CONCLUSION: TCM following ablation may prolong PFS and suppress recurrence in patients with HCC, with continuous oral administration for more than 2 years maybe experience a greater benefit. The TSEs of the treatment are mild and can be tolerated.

15.
Small ; : e2102602, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34339104

RESUMO

In this study, high-purity and centimeter-scale bulk Ta2 Ni3 Se8 crystals are obtained by controlling the growth temperature and stoichiometric ratio between tantalum, nickel, and selenium. It is demonstrated that the bulk Ta2 Ni3 Se8 crystals could be effectively exfoliated into a few chain-scale nanowires through simple mechanical exfoliation and liquid-phase exfoliation. Also, the calculation of electronic band structures confirms that Ta2 Ni3 Se8 is a semiconducting material with a small bandgap. A field-effect transistor is successfully fabricated on the mechanically exfoliated Ta2 Ni3 Se8 nanowires. Transport measurements at room temperature reveal that Ta2 Ni3 Se8 nanowires exhibit ambipolar semiconducting behavior with maximum mobilities of 20.3 and 3.52 cm2 V-1 s-1 for electrons and holes, respectively. The temperature-dependent transport measurement (from 90 to 295 K) confirms the carrier transport mechanism of Ta2 Ni3 Se8 nanowires. Based on these characteristics, the obtained 1D vdW material is expected to be a potential candidate for additional 1D materials as channel materials.

16.
Neurol Res ; : 1-10, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229565

RESUMO

Background: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events.Methods: HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE.Results: Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182-11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481-13.030) were significantly associated with acute ischemic events.Conclusion: Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.

17.
ACS Nano ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236829

RESUMO

Polymeric chains made of "giant" monomers at a larger length scale provide intriguing insights into the fundamental principles of polymer science. In this study, we modularly prepared a library of discrete amphiphilic polymeric chains using molecular nanoparticles as repeat units, with exact control of composition, chain length, surface property, and regio-configuration. These giant polymeric chains self-assembled into a rich collection of highly ordered phases. The precise chemical structure and uniform chain length eliminate all the inherent molecular "defects", while the nanosized monomer amplifies minute structural differences, providing an ideal platform for a systematic scrutiny of the self-assembly behaviors at a larger length scale. The compositional and regio-configurational contribution was carefully studied. The regio-regularity is found to have a direct and profound impact on the chain conformation, leading to a distinct molecular packing scheme and therefore shifting the phase boundaries. With increasing the length of the linker, the regio-constraint gradually diminishes, and the neighboring particles would eventually be decoupled.

18.
BMC Infect Dis ; 21(1): 668, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243716

RESUMO

BACKGROUND: To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. METHODS: Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. RESULTS: A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). CONCLUSIONS: The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Emtricitabina/uso terapêutico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Farmacorresistência Viral/genética , Epidemias , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto Jovem
19.
J Am Chem Soc ; 143(29): 11141-11151, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34279908

RESUMO

Small-ring silacycles are important organosilane species in main-group chemistry and have found numerous applications in organic synthesis. 3-Silaazetidine, a unique small silacycle bearing silicon and nitrogen atoms, has not been adequately explored due to the lack of a general synthetic scheme and its sensitivity to air. Here, we describe that 3-silaazetidine can be easily prepared in situ from diverse air-stable precursors (RSO2NHCH2SiR12CH2Cl). 3-Silaazetidine shows excellent functional group tolerance in a palladium-catalyzed ring expansion reaction with terminal alkynes, giving 3-silatetrahydropyridines and diverse silaazacycle derivatives, which are promising ring frameworks for the discovery of Si-containing functional molecules.

20.
Ann Palliat Med ; 10(7): 8512-8517, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263614

RESUMO

Immune checkpoint inhibitors can cause immune-related toxicity in various systems, and myocarditis is the most serious life-threatening toxicity. This report introduces diagnosis and treatment of two cases which developed myocarditis after receiving PD-1 inhibitors therapy. The first case was a 77-year-old male with chordoma, who was treated by third-line sintilimab combined with anlotinib, and presented with symptoms of chest tightness, shortness of breath and upper eyelid ptosis three weeks later. He was diagnosed as immune-checkpoint-inhibitors-related myocarditis and myositis-myasthenia-gravis overlap syndrome based on his clinical symptoms, serum biomarkers, electrocardiogram, echocardiogram, and characteristic findings on cardiac 18F-FDG PET-MRI. Methylprednisolone was given 480 mg/d initially and was gradually reduced to 40 mg/d in 4 weeks, with the myocardial injury biomarkers declined in the same time. The second case was a 69-year-old female with advanced non-small cell lung cancer, who was treated by pemetrexed combined with bevacizumab and camrelizumab, and presented with palpitations 20 days later. She was diagnosed as immune-checkpoint-inhibitors-related myocarditis based on her clinical symptoms, serum biomarkers, electrocardiogram and echocardiogram. Methylprednisolone was given 240 mg/d initially and was gradually reduced to 40 mg/d with good response of myocardial injury biomarkers decline. However, the patient developed fatal myasthenia gravis afterwards, with little response to all treatments. These two cases revealed that, early detection and timely intervention, including discontinuation of immune checkpoint inhibitors and initiation of adequate steroid therapy, can reduce morbidity and mortality and improve prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Miocardite , Miosite , Idoso , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/tratamento farmacológico
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