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1.
Anal Methods ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35043798

RESUMO

In this work, a ratiometric fluorescence system was designed for the detection of trace UO22+ in water based on the inner filter effect (IFE) between gold nanoparticles (AuNPs) and gold nanoclusters (AuNCs). IFE-induced fluorescence quenching was achieved due to the enhanced complementary overlap between the absorption spectra of AuNPs and the emission spectrum of AuNCs after the addition of UO22+. Blue carbon dots (B-CDs) were added to serve as reference fluorophores to expand the color tonality and make human eye recognition easier. The ratiometric fluorescent sensor demonstrated a unique fluorescence color change from red to blue when different doses of UO22+ were added, with a detection limit of 8.4 nM. Furthermore, the ratiometric fluorescent sensor was effectively used for UO22+ determination in real-world water samples, with acceptable recoveries.

2.
Sci Rep ; 12(1): 578, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022480

RESUMO

Cervical lymph node metastasis (CLNM) is common in patients with papillary thyroid carcinoma (PTC), which is responsible for tumor staging and surgical strategy. The accurate preoperative identification of CLNM is essential. In this study, twenty consecutive patients with PTC received a parenchyma injection of Sonazoid followed by contrast enhanced ultrasound (CEUS) to identify CLNM. The specific lymphatic CEUS (LCEUS) signs for diagnosing CLNM were summarized, which were further compared with the resected specimens to get the pathological basis. After the injection of contrast agent, lymphatic vessel and lymph node (LN) could be exclusively displayed as hyperperfusion on LCEUS. The dynamic perfusion process of contrast agent in CLNM over time can be clearly visualized. Perfusion defect and interruption of bright ring were the two characteristic LCEUS signs in diagnosing CLNM. After comparing with pathology, perfusion defect was correlated to the metastatic foci in medulla and interruption of bright ring was correlated to the tumor seeding in marginal sinus (all p values < 0.001). The diagnostic efficacies of these two signs were high (perfusion defect vs. interruption of bright ring: AUC, 0.899, 95% CI 0.752-1.000 vs. 0.904, 0.803-1.000). LCEUS has advantages in identifying CLNM from PTC. The typical LCEUS signs of CLNM correlated with pathology.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120435, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34607093

RESUMO

As a member of the reactive oxygen species, hydrogen peroxide (H2O2) plays critical roles in oxidative stress and cell signaling. Intracellular abnormal levels of H2O2 production are closely related to many diseases. Therefore, the real-time monitoring of H2O2 in the cells is important. In this work, we designed a novel fluorescent probe (Mito-H2O2) for the specific detection of H2O2 based on the hemicyanine skeleton, with bright near-infrared fluorescence emission. Mito-H2O2 displayed fast response, excellent water-solubility and great fluorescence intensity enhancement after the addition of H2O2. Furthermore, Mito-H2O2 has been successfully applied to image both of the exogenous and endogenous H2O2 in cells and mice with negligible cytotoxity.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Animais , Carbocianinas , Células HeLa , Humanos , Camundongos , Esqueleto
4.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166283, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601015

RESUMO

Advanced glycation end products (AGEs) play a critical pathogenic role in the development of diabetic complications. Recent studies have shown that diabetes is associated with not only abnormal glucose metabolism but also abnormal ribose and fructose metabolism, although glucose is present at the highest concentration in humans. The glycation ability and contribution of ribose and fructose to diabetic complications remain unclear. Here, the glycation ability of ribose, fructose and glucose under a mimic physiological condition, in which the concentration of ribose or fructose was one-fiftieth that of glucose, was compared. Bovine serum albumin (BSA) was used as the working protein in our experiments. Ribose generated more AGEs and was markedly more cytotoxic to SH-SY5Y cells than fructose. The first-order rate constant of ribose glycation was found to be significantly greater than that of fructose glycation. LC-MS/MS analysis revealed 41 ribose-glycated Lys residues and 12 fructose-glycated residues. Except for the shared Lys residues, ribose reacted selectively with 17 Lys, while no selective Lys was found in fructose-glycated BSA. Protein conformational changes suggested that ribose glycation may induce BSA into amyloid-like monomers compared with fructose glycation. The levels of serum ribose were correlated positively with glycated serum protein (GSP) and diabetic duration in type 2 diabetes mellitus (T2DM), respectively. These results indicate that ribose has a greater glycation ability than fructose, while ribose largely contributes to the production of AGEs and provides a new insight to understand in the occurrence and development of diabetes complications.


Assuntos
Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , Produtos Finais de Glicação Avançada/genética , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Cromatografia Líquida , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Frutose/sangue , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Glicosilação , Humanos , Ribose/sangue , Espectrometria de Massas em Tandem
5.
Dis Markers ; 2021: 7190301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868396

RESUMO

Background: The SOX gene family has been proven to display regulatory effects on numerous diseases, particularly in the malignant progression of neoplasms. However, the molecular functions and action mechanisms of SOX genes have not been clearly elucidated in clear cell renal cell carcinoma (ccRCC). We aimed to explore the expression status, prognostic values, clinical significances, and regulatory actions of SOX genes in ccRCC. Methods: RNA-sequence data and clinical information derived from The Cancer Genome Atlas (TCGA) database was used for this study. Dysregulated SOX genes between the normal group and ccRCC group were screened using the Wilcoxon signed-rank test. The Kaplan-Meier analysis and univariate Cox analysis methods were used to estimate the overall survival (OS) and disease-specific survival (DSS) differences between different groups. The independent prognostic factors were identified by the use of uni- and multivariate assays. Subsequently, the Wilcoxon signed-rank test or Kruskal-Wallis test and the chi-square test or Fisher exact probability methods were employed to explore the association between clinicopathological variables and SOX genes. Finally, CIBERSORT was applied to study the samples and examine the infiltration of immune cells between different groups. Results: Herein, 12 dysregulated SOX genes in ccRCC were screened. Among them, two independent prognostic SOX genes (SOX6 and SOX12) were identified. Further investigation results showed that SOX6 and SOX12 were distinctly associated with clinicopathological features. Furthermore, functional enrichment analysis revealed that SOX6 and SOX12 were enriched in essential biological processes and signaling pathways. Finally, we found that the SOX6 and SOX12 expression levels were correlated with tumor-infiltrating immune cells (TIICs). Conclusion: The pooled analyses showed that SOX6 and SOX12 could serve as promising biomarkers and therapeutic targets of patients with ccRCC.

6.
Lung Cancer ; 163: 27-34, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894456

RESUMO

OBJECTIVE: Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer. MATERIALS AND METHODS: Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively. RESULTS: By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. CONCLUSIONS: We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

7.
Front Cardiovasc Med ; 8: 685970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901200

RESUMO

Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS. Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders. Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12-1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48-0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (P I < 0.004-0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22-0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04-0.36) decreased the risk of IS (P I < 0.0001). Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34844855

RESUMO

Cyanide (CN-) is a highly toxic compound that exists in many substances and is harmful to the environment and human health. Therefore, it is of great significance to develop excellent CN- ion probes, especially solvent-induced on-off fluorescent probes. Based on the condensation reaction of indolo[2,1-b][1,3]oxazine molecules with aldehydes, probes (E)-13a-(2-(9-ethyl-9H-carbazol-3-yl)vinyl)-14,14-dimethyl-10-nitro-13a,14-dihydro-8H-benzo[e]benzo[5,6][1,3]oxazino[3,2-a]indole (NCO) and (E)-13a-(2-(9-benzyl-9H-carbazol-3-yl)vinyl)-14,14-dimethyl-10-nitro-13a,14-dihydro-8H-benzo[e]benzo[5,6][1,3]oxazino[3,2-a]indole (NBO) were synthesized to detect CN-. Compared with other cyanogen ion probes, NCO and NBO have special carbazole ring structures and large conjugate systems. When CN- is added to the probe-detection solution, color changes that are visible to the naked eye can occur. The UV-vis spectrum test using differential spectroscopy shows that the probe (i) has excellent solvent-induced switching characteristics and stability (CH3OH-H2O) and (ii) high selectivity, anti-interference ability, and sensitivity for the detection of CN-. The fluorescence limit of detections (LODs) are 1.05 µM for NCO and 1.34 µM for NBO. The UV LODs are 0.83 µM for NCO and 0.87 µM for NBO. Fluorescence spectroscopy shows that the probe has remarkable fluorescence properties. Fluorescence titration experiments, liver cancer cell (Hep G2) imaging, and cytotoxicity experiments all show that the probes have high biocompatibility, low toxicity, high cell permeability, and high sensitivity for the detection of CN- in cells. In addition, NCO and NBO have been successfully used for the detection of cyanogenic glycosides in the seeds of ginkgo, crabapple, apple, and cherry. Test strips were fabricated to detect CN-. After adding CN-, the color of the test strip changed significantly-from brown to light yellow; thus, the test strips have a high application value in the fields of drug quality control, drug safety testing, and pharmacological research.

9.
Front Med (Lausanne) ; 8: 656066, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746160

RESUMO

Background: Fungal infections of the central nervous system (CNS) are not commonly seen clinically. Clinical diagnosis of fungal infections often depend on the pathogen culture and the clinical features. This method is time-consuming and insensitive, which can lead to misdiagnosis. The authors introduce an adult patient with fungal infections diagnosed by next-generation sequencing (NGS). Case: The patient was a 60-year-old male Chinese who had both hypermyotonia of the lower extremities and fever. The auxiliary examinations such as MRI, CT, and cerebrospinal fluid (CSF) analysis showed obvious abnormalities. Because of the difficulties in diagnosis, it was hard to determine the treatment plan. The NGS detected specific sequences of Candida albicans in 3 days. The patient was then treated with liposomal amphotericin B and fluconazole. About 3 weeks later, the symptoms of the patient improved significantly and he was discharged from the hospital. Conclusion: Compared with the routine cultural method, NGS has made a huge advancement in infection diagnosis and targeting antimicrobial therapy for CNS infection.

10.
ACS Omega ; 6(45): 30826-30833, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34805711

RESUMO

Plant bacteria such as Xanthomonas axonopodis pv. citri (Xac), Pseudomonas syringae pv. actinidiae (Psa), Xanthomonas oryzae pv. oryzae (Xoo), and tobacco mosaic virus (TMV) have created huge obstacles to the global trade of food and economic crops. However, traditional chemical agents used to control these plant diseases have gradually become disadvantageous due to long-term irregular use. Therefore, finding new and efficient antibacterial and antiviral agents is becoming imperative. In this study, a series of myricetin derivatives containing a quinazolinone moiety were designed and synthesized, and the antibacterial and antiviral activities of these compounds were evaluated. The bioassay results showed that some target compounds exhibited good antibacterial activities in vitro and antiviral activities in vivo. Among them, the median effective concentration (EC50) value of compound L18 against Xac was 16.9 µg/mL, which was better than those of the control drugs bismerthiazol (BT) (62.2 µg/mL) and thiodiazole copper (TC) (97.5 µg/mL). Scanning electron microscopy (SEM) results confirmed that compound L18 inhibited the growth of Xac by affecting the morphology of cells. Microscale thermophoresis (MST) test results indicated that the dissociation constant (K d) value of compound L11 against TMV-CP was 0.012 µM, which was better than that of the control agent ningnanmycin (2.726 µM). This study reveals that myricetin derivatives containing a quinazolinone moiety are potential antibacterial and antiviral agents.

11.
BMC Ophthalmol ; 21(1): 402, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809591

RESUMO

BACKGROUND: The use of Spectral domain optical coherence tomography (SD-OCT) to evaluate the predictors of visual acuity-recovery in patients treated with conbercept for macular edema (ME) secondary to central retinal vein occlusion (CRVO) has rarely been seen. We collected 26 CRVO-ME patients with different OCT measures at 6 months follow-up to identify the factors that are most strongly correlated with the best-corrected visual acuity (BCVA) post-treatment in CRVO-ME patients treated with conbercept. PURPOSE: To evaluate the effectiveness of intravitreal conbercept injections for the treatment of CRVO-ME and to determine the major predictors of best-corrected visual acuity (BCVA) post-treatment. METHODS: A retrospective study methodology was used. Twenty-six eyes from 26 patients with CRVO-ME were enrolled in the study. After an initial intravitreal injection of conbercept (0.5 mg/0.05 ml), monthly injections for up to 6 months were given following a 1 + PRN (pro re nata) regimen. Data collected at monthly intervals included measurements of the logMAR BCVA, central subfield thickness (CST), macular volume (MV), photoreceptor layer thickness (PLT), outer nuclear layer thickness (ONLT), and the disrupted ellipsoid zone (DEZ). The correlation between BCVA, before and after injections, and each of CST, MV, PLT, ONLT, DEZ was analyzed. RESULTS: The logMAR BCVA in months 3 and 6 post-injection was significantly improved relative to the baseline. In this same period the CST, MV, PLT, ONLT and DEZ were also significantly improved relative to the baseline. There was a negative correlation between PLT and logMAR BCVA at months 3 and 6 after treatment (r = - 0.549, P < 0.001; r = - 0.087, P < 0.001). CONCLUSION: Intravitreal injection of conbercept is an effective treatment for CRVO-ME. With 6 months of follow-up, logMAR BCVA and CST, MV, PLT, ONLT, DEZ improved. PLT was negatively correlated with the visual function in CRVO-ME patients after conbercept treatment, which may be a predictor of vision recovery in patients with CRVO-ME.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Inibidores da Angiogênese/uso terapêutico , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Proteínas Recombinantes de Fusão , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
12.
Luminescence ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730276

RESUMO

Uranium is an important nuclear fuel and the risk of human exposure to uranium increases as increasing amounts of uranium-containing waste enter the environment due to the rapid growth of nuclear power. Therefore, rapid, sensitive, and portable uranium detection is a promising approach to effectively control and monitor uranium contamination. To achieve this goal, abundant oxygen- and nitrogen-containing groups were introduced to molybdenum oxide quantum dot (MoOx QDs) surfaces with dopamine (DA) modification. Due to the excellent coordination ability of oxygen- and nitrogen-containing groups with uranium, the obtained DA-functionalized MoOx QDs (DA-MoOx QDs) showed a strong binding affinity for uranium and sensitivity was increased nearly 1000-fold compared with MoOx QDs alone. The limit of detection was 3.85 nM, which is higher than most of the reported nanomaterials. Moreover, the DA-MoOx QD-based method showed high selectivity and uranium could be clearly detected under masking with ethylenediaminetetraacetic acid even when the concentration of other metal ions was 100-fold higher than that of uranium, showing a very promising method for uranium contamination control and monitoring.

13.
Front Pediatr ; 9: 665377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631608

RESUMO

Objective: Aimed to investigate the epidemiological characteristics, clinical features, treatment, and short-term prognosis of COVID-19 in children. Methods: Retrospective analysis was conducted in 48 children with COVID-19 admitted to 12 hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020. Results: Of the 48 cases, Familial clusters were confirmed for 46 children (96%). 16 (33%) were imported from other provinces. There were 11 (23%) asymptomatic cases. only 2 cases (4%) were severe. The most common symptom was fever (n = 20, 42%). Other symptoms included cough (n = 19, 40%), fatigue (n = 8, 17%), and diarrhea (n = 5, 10%). In the early stage, the total peripheral blood leukocytes count increased in 3(6%) cases and the lymphocytes count decreased in 5 (10%) cases. C-reactive protein and procalcitonin were elevated respectively in 3 (6%) cases and 2 (4%) cases. There were abnormal chest CT changes in 22 (46%) children, including 15 (68%) with patchy ground glass opacity, 5 (22%) with consolidation, and 2 (10%) with mixed shadowing. In addition to supportive treatment, antiviral therapy was received by 41 (85%) children, 11 (23%) patients were treated with antibiotics, and 2 (4%) were treated with methylprednisolone and intravenous immunoglobulin. Compared to 2 weeks follow-up, one child developed low fever and headache during the 4 weeks follow-up, 3 (6%) children had runny noses, one of them got mild cough, and 4 (12%) children had elevated white blood cells and lymphocytes. However, LDH and CK increased at 2 weeks and 4 weeks follow-up. 2 weeks follow-up identified normal chest radiographs in 33 (69%) pediatric patients. RT-PCR detection of SARS-CoV-2 was negative in all follow-up patients at 2 and 4 weeks follow-up. All 48 pediatric patients were visited by calling after 1 year of discharge. Conclusions: Most cases of COVID-19 in children in Hunan province were asymptomatic, mild, or moderate. Close family contact was the main route of infection. It appeared that the younger the patient, the less obvious their symptoms. Epidemiological history, nucleic acid test, and chest imaging were important tools for diagnosis in children.

14.
Food Res Int ; 149: 110660, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600662

RESUMO

A cross-modal interaction may exist between the perception of saltiness and the pungency elicited by Sichuan pepper oleoresin (Spo). Thirty-one hypersensitive panelists were selected to participate in this study. Spo solutions dissolved in different NaCl concentrations, ranging from 1.25 g/L to 167.9 g/L, were used as the test samples. The rated difference from control, the generalized labeled magnitude scale (gLMS), and the time-intensity (TI) method were used to determine the detection threshold (DT), the recognition threshold (RT), the intensity, and the dynamic perception of pungent sensation. The results revealed that the pungency thresholds increased significantly (p < 0.01) in the solution with a high NaCl (167.9 g/L) concentration. Furthermore, high NaCl solutions suppressed the pungency intensity at all Spo concentrations except for 0.02 g Spo/L in water (p < 0.05). The TI and principal component analysis (PCA) results showed that an increase in the Spo concentration prolonged the duration of the pungency sensation. However, the maximum intensity, the time to reach maximum intensity, the decay time of perception, and the end time of perception of the Spo solutions ranging from 2.13 g/L to 4.69 g/L were significantly reduced at medium (42.95 g/L) and high NaCl concentrations. Since the salty and pungency sensations exhibited by NaCl and Spo are common flavor combinations in food products and dishes, studying the influence of saltiness on the dynamic perception of pungent sensation not only aids the development of oral cleaners during pungency evaluation but also presents significant theoretical and practical value in creating pungent food and cuisine based on consumer preferences.


Assuntos
Sensação , Cloreto de Sódio , Percepção , Extratos Vegetais , Verduras
15.
J Am Chem Soc ; 143(43): 17958-17963, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34665638

RESUMO

The development of helicene molecules with significant chiroptical responses covering a broad range of the visible spectrum is highly desirable for chiral optoelectronic applications; however, their absorption dissymmetry factors (gabs) have been mostly lower than 0.01. In this work, we report unprecedented B,N-embedded double hetero[7]helicenes with nonbonded B and N atoms, which exhibit excellent chiroptical properties, such as strong chiroptical activities from 300 to 700 nm, record high gabs up to 0.033 in the visible spectral range, and tunable circularly polarized luminescence (CPL) from red to near-infrared regions (600-800 nm) with high photoluminescence quantum yields (PLQYs) up to 100%. As revealed by theoretical analyses, the high gabs values are related to the separate molecular orbital distributions owing to the incorporation of nonbonded B and N atoms. The new type of B,N-embedded double heterohelicenes opens up an appealing avenue to the future exploitation of high-performance chiroptical materials.

16.
Front Pharmacol ; 12: 722122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675804

RESUMO

Objective: To compare the efficacy of various listed Chinese patent medicines combined with letrozole in the treatment of ovulation disorders using network meta-analysis (NMA). Methods: We conducted a systematic literature search in PubMed, Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, Wanfang, and VIP Information databases up to June 2020. Randomized controlled trials reporting Chinese patent medicine combined with letrozole for ovulation disorders were included. The Stata 13 and WinBUGS1.43 software were used for data analysis. Results: A total of 24 randomized controlled trials were included, involving 2,318 patients. The results showed that when compared with patients using only letrozole, the ovulation rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, or Dingkun Dan, and Fufan Xuanju capsules showed the greatest improvement; the pregnancy rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, or Dingkun Dan; and the endometrial thickness on the day of follicular maturity was greater in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, Bailing capsules, or Dingkun Dan. In terms of the sequencing of NMA results, Fufang Xuanju capsules combined with letrozole gave the best results in improving the ovulation rate and increasing the endometrial thickness, while Dingkun Dan combined with letrozole achieved the best results for improving the pregnancy rate. Conclusion: Letrozole combined with Chinese patent medicine is more effective than letrozole alone in the treatment of ovulation disorders. Fufang Xuanju capsules is good at improving the ovulation rate and increasing the endometrial thickness. Dingkun Dan is good at improving the pregnancy rate. The appropriate choice of treatment should be made according to the actual clinical situation. This study is registered with the International Prospective Register of Systematic Reviews (CRD42020200603).

17.
Gastroenterol Rep (Oxf) ; 9(4): 329-338, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34567565

RESUMO

Background: Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%-40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. Methods: A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n = 240) and a validation cohort (n = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. Results: The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. Conclusions: We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making.

18.
Cell Death Discov ; 7(1): 260, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552057

RESUMO

To maintain genomic stability, the mammalian cells has evolved a coordinated response to DNA damage, including activation of DNA repair and cell cycle checkpoint processes. Exonuclease 1 (EXO1)-dependent excision of DNA ends is important for the initiation of homologous recombination (HR) repair of DNA breaks, which is thought to play a key role in activating the ATR-CHK1 pathway to induce G2/M cell cycle arrest. But the mechanism is still not fully understood. Here, we report that ZGRF1 forms complexes with EXO1 as well as other repair proteins and promotes DNA repair through HR. ZGRF1 is recruited to DNA damage sites in a MDC1-RNF8-BRCA1 dependent manner. Furthermore, ZGRF1 is important for the recruitment of RPA2 to DNA damage sites and the following ATR-CHK1 mediated G2/M checkpoint in response to irradiation. ZGRF1 null cells show increased sensitivity to many DNA-damaging agents, especially PARPi and irradiation. Collectively,our findings identify ZGRF1 as a novel regulator of DNA end resection and G2/M checkpoint. ZGRF1 is a potential target of radiation and PARPi cancer therapy.

19.
Brain Res ; 1772: 147663, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555415

RESUMO

Neuropathic pain is a common complication of diabetes mellitus with poorly relieved by conventional analgesics. Metformin, a first-line drug for type 2 diabetes, reduces blood glucose by activating adenosine monophosphate protein kinase (AMPK) signalling system. However, the effect of Metformin on diabetic neuropathic pain is still unknown. In the present study, we showed that Metformin was capable of attenuating diabetes induced mechanical allodynia, and the analgesia effect could be blocked by Compound C (an AMPK inhibitor). Importantly, Metformin enhanced the phosphorylation level of AMPK in L4-6 DRGs of diabetic rats but not affect the expression of total AMPK. Intrathecal injection of AICAR (an AMPK agonist) could activate AMPK and alleviate the mechanical allodynia of diabetic rats. Additionally, phosphorylated AMPK and NF-κB was co-localized in small and medium neurons of L4-6 DRGs. Interestingly, the regulation of NF-κB in diabetic rats was obviously reduced when AMPK was activated by AICAR. Notably, Metformin could decrease NF-κB expression in L4-6 DRGs of diabetic rats, but the decrease was blocked by Compound C. In conclusion, Metformin alleviates diabetic mechanical allodynia via activation of AMPK signaling pathway in L4-6 DRGs of diabetic rats, which might be mediated by the downregulation of NF-κB, and this providing certain basis for Metformin to become a potential drug in the clinical treatment of diabetic neuropathic pain.

20.
J Cancer ; 12(20): 6209-6215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539894

RESUMO

Background: Weekly and triweekly cisplatin-based concurrent chemoradiotherapy (CCRT) have been used in the treatment of nasopharyngeal carcinoma (NPC). Objective: This study aimed to compare the benefits and risks between the two treatments. Methods: We systematically searched electronic databases for prospective and retrospective clinical studies of NPC patients who received weekly compared with triweekly cisplatin-based CCRT. The primary endpoints comprised overall, failure-free, distant metastasis-free, and locoregional recurrence-free survivals (OS, FFS, DMFS, and LRFS). Secondary endpoints were toxicities. Results: Six studies were included in the systematic review, of which four with 1515 NPC patients were eligible for further pooled analysis. There were no significant differences between weekly and triweekly groups in terms of 5-year OS (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.51-1.79), FFS (OR 1.09, 95% CI 0.67-1.76), DMFS (OR 1.25, 95% CI 0.54-2.92), and LRFS (OR 0.83, 95% CI 0.55-1.25). For grade ≥ 3 toxicities, the weekly group had higher risks of anemia (risk ratio [RR] 2.96, 95% CI 1.12-7.81) and thrombocytopenia (RR 2.75, 95% CI 1.54-4.90), but a lower incidence of vomiting (RR 0.34, 95% CI 0.18-0.63) versus the triweekly group. Conclusion and Relevance: Both weekly and triweekly schedules could be recommended to NPC patients during CCRT. Additionally, hematologic adverse events in weekly strategy and non-hematologic adverse events in triweekly strategy are of higher concern.

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