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1.
PLoS One ; 19(7): e0306694, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980844

RESUMO

Serial correlations within temperature time series serve as indicators of the temporal consistency of climate events. This study delves into the serial correlations embedded in global surface air temperature (SAT) data. Initially, we preprocess the SAT time series to eradicate seasonal patterns and linear trends, resulting in the SAT anomaly time series, which encapsulates the inherent variability of Earth's climate system. Employing diverse statistical techniques, we identify three distinct types of serial correlations: short-term, long-term, and nonlinear. To identify short-term correlations, we utilize the first-order autoregressive model, AR(1), revealing a global pattern that can be partially attributed to atmospheric Rossby waves in extratropical regions and the Eastern Pacific warm pool. For long-term correlations, we adopt the standard detrended fluctuation analysis, finding that the global pattern aligns with long-term climate variability, such as the El Niño-Southern Oscillation (ENSO) over the Eastern Pacific. Furthermore, we apply the horizontal visibility graph (HVG) algorithm to transform the SAT anomaly time series into complex networks. The topological parameters of these networks aptly capture the long-term correlations present in the data. Additionally, we introduce a novel topological parameter, Δσ, to detect nonlinear correlations. The statistical significance of this parameter is rigorously tested using the Monte Carlo method, simulating fractional Brownian motion and fractional Gaussian noise processes with a predefined DFA exponent to estimate confidence intervals. In conclusion, serial correlations are universal in global SAT time series and the presence of these serial correlations should be considered carefully in climate sciences.


Assuntos
Temperatura , Algoritmos , Clima , Fatores de Tempo , Estações do Ano , El Niño Oscilação Sul
2.
Cardiovasc Toxicol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008240

RESUMO

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

3.
Eur J Pharmacol ; 978: 176749, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38897444

RESUMO

A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.


Assuntos
Antraquinonas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Metabolismo Energético , Hiperalgesia , Camundongos Endogâmicos C57BL , Mitocôndrias , Neuralgia , Neurônios , Oxirredução , Animais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico
4.
Front Neurol ; 14: 1277366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020615

RESUMO

Background: As there is still no consensus on the treatment of carotid stent thrombosis (CST), we would like to describe our experience with the revascularization of CST by mechanical thrombectomy. Methods: We retrospectively studied patients who underwent mechanical thrombectomy after CST at Xuzhou Municipal First People's Hospital and Xuzhou Central Hospital between January 2020 and November 2022. The results of the procedures, complications, and clinical and imaging follow-up were recorded. Results: A total of six patients were included in this study. The stenosis grade before stent implantation was ≥85% in all patients, and the stenosis length ranged from 7 to 20 mm. Patients experienced CST within 6 days to 45 months after carotid artery stenting (CAS); the median admission on the National Institutes of Health Stroke Scale (NIHSS) at CST was 12 (range 8-25). Mechanical thrombectomy was successfully performed in all patients. There was no periprocedural death, and the modified Rankin Scale (mRS) at the 3-month follow-up was 0-2. All patients showed recovery from their neurological deficits. Conclusion: The treatment of symptomatic CST with mechanical thrombectomy resulted in satisfactory clinical outcomes. This regimen could be effective and safe, and future prospective and randomized studies are warranted.

5.
Clin Endocrinol (Oxf) ; 99(1): 92-102, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029081

RESUMO

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.


Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
6.
Small ; 19(23): e2207093, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36890773

RESUMO

Lithium metal batteries (LMBs) are promising for next-generation high-energy-density batteries owing to the highest specific capacity and the lowest potential of Li metal anode. However, the LMBs are normally confronted with drastic capacity fading under extremely cold conditions mainly due to the freezing issue and sluggish Li+ desolvation process in commercial ethylene carbonate (EC)-based electrolyte at ultra-low temperature (e.g., below -30 °C). To overcome the above challenges, an anti-freezing carboxylic ester of methyl propionate (MP)-based electrolyte with weak Li+ coordination and low-freezing temperature (below -60 °C) is designed, and the corresponding LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode exhibits a higher discharge capacity of 84.2 mAh g-1 and energy density of 195.0 Wh kg-1 cathode than that of the cathode (1.6 mAh g-1 and 3.9 Wh kg-1 cathode ) working in commercial EC-based electrolytes for NCM811‖ Li cell at -60 °C. Molecular dynamics simulation, Raman spectra, and nuclear magnetic resonance characterizations reveal that rich mobile Li+ and the unique solvation structure with weak Li+ coordination are achieved in MP-based electrolyte, which collectively facilitate the Li+ transference process at low temperature. This work provides fundamental insights into low-temperature electrolytes by regulating solvation structure, and offers the basic guidelines for the design of low-temperature electrolytes for LMBs.

7.
Signal Transduct Target Ther ; 8(1): 14, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617552

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Identification of the underlying mechanism of HCC progression and exploration of new therapeutic drugs are urgently needed. Here, a compound library consisting of 419 FDA-approved drugs was taken to screen potential anticancer drugs. A series of functional assays showed that desloratadine, an antiallergic drug, can repress proliferation in HCC cell lines, cell-derived xenograft (CDX), patient-derived organoid (PDO) and patient-derived xenograft (PDX) models. N-myristoyl transferase 1 (NMT1) was identified as a target protein of desloratadine by drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) assays. Upregulation of NMT1 expression enhanced but NMT1 knockdown suppressed tumor growth in vitro and in vivo. Metabolic labeling and mass spectrometry analyses revealed that Visinin-like protein 3 (VILIP3) was a new substrate of NMT1 in protein N-myristoylation modification, and high NMT1 or VILIP3 expression was associated with advanced stages and poor survival in HCC. Mechanistically, desloratadine binds to Asn-246 in NMT1 and inhibits its enzymatic activity, disrupting the NMT1-mediated myristoylation of the VILIP3 protein and subsequent NFκB/Bcl-2 signaling. Conclusively, this study demonstrates that desloratadine may be a novel anticancer drug and that NMT1-mediated myristoylation contributes to HCC progression and is a potential biomarker and therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Ácido Mirístico/metabolismo , Processamento de Proteína Pós-Traducional
8.
ACS Appl Mater Interfaces ; 15(2): 3633-3643, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598181

RESUMO

In this study, a tungstated zirconia (WOx/ZrO2) catalyst was developed for the continuous synthesis of adiponitrile (ADN) by gas-phase nitrilation of dimethyl adipate (DMA) with NH3. The highest TOFADN could be reached on WOx/ZrO2 bearing ∼1D WOx species (highly dispersed and discontinuous status) at the surface, which, however, delivered the poorest selectivity toward nitrilation (SADN+MCP). In comparison, both efficient and selective transformation of DMA to ADN was achieved by fabricating WOx/ZrO2 with continuously distributed oligomeric WOx species (∼2D) at the surface, either by varying the dosage of the W-reagent in the preparation of WOx(m)/ZrO2 or by doping a proper amount of the Mn element into WOx(5.0)/ZrO2, bearing WO3 NPs. Furthermore, the in situ diffuse reflectance infrared Fourier transform spectroscopy investigations of both independent and competitive adsorptions of ester functionality and NH3 over W-O-Zr, W-O-W, and Zr-O-Zr boundaries at the surface clarified the synergistic effect of these species in the activation of DMA/NH3 and thereby nitrilation.

9.
J Plast Surg Hand Surg ; 57(1-6): 129-136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34978504

RESUMO

To investigate the role of a disintegrin and metalloprotease protein 17 (ADAM17) in regulating the proliferation and extracellular matrix (ECM) expression of keloid fibroblasts (KFs) via the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway. ADAM17 expression in keloid tissues was detected by western blotting. KFs were isolated, cultured and divided into the control, shNC (negative control), shADAM17, transforming growth factor-ß1 (TGF-ß1), TGF-ß1 + shNC and TGF-ß1 + shADAM17 groups. The expression of ECM was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Western blotting was performed to detect the expression of proteins. Cell proliferation was detected by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, while cell invasion and migration were examined by Transwell and wound healing assays. The expression of ADAM17 was increased in keloid tissues and KFs. Compared with the control group, the expression of p-EGFR and p-ERK/1/2/ERK1/2, as well as the expression of collagen I, collagen III, connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), were decreased in KFs from the shADAM17 group, with decreased cell proliferation, invasion and migration. In contrast, the TGF-ß1 group presented the opposite trend in these aspects. In addition, compared with the TGF-ß1 group, KFs from the TGF-ß1 + shADAM17 group had decreased ECM expression, proliferation, invasion and migration. ADAM17 expression was upregulated in keloid tissues. Silencing ADAM17 may inhibit the activity of the EGFR/ERK pathway to limit the deposition of ECM in KFs with reduced proliferation, invasion and migration.


Assuntos
Queloide , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Queloide/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Transdução de Sinais , Colágeno/metabolismo , Proliferação de Células , Receptores ErbB/metabolismo , Fibroblastos/patologia , Células Cultivadas , Proteína ADAM17/genética , Proteína ADAM17/metabolismo
10.
Heliyon ; 8(12): e12162, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36536911

RESUMO

Objective: To evaluate the clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL). Methods: We retrospectively reviewed the clinical data of 8 patients who were considered suspected cases of PCNSL by multimodal imaging techniques. The final pathologic diagnosis were determined by the frameless robotic stereotactic biopsy. The postoperative related complications and pathological results were analyzed. Results: All patients underwent biopsies under general anesthesia with an average surgery time of 29.5 ± 4.5 min. The final pathological diagnostic accordant rate with the preoperative ones was 100%, and the pathologic examination of our patients showed features of diffuse large B-cell lymphoma. During the surgery, one patient suffered intratumoral hemorrhage without leading to serious cerebral edema, and conservative treatment was given. There was no death occurring during the study, and there were no significant differences in the Karnofsky Performance Scale Scores of all patients before and after surgery. Finally, they were transferred to the hematology department for standardized chemoradiotherapy according to the pathological results of PCNSL. Conclusion: This study shows that it may play a vital role in the early diagnosis of PCNSL with the technique of multimodal imaging. The technique of frameless robotic stereotactic biopsy for obtaining the pathology outcomes in suspected PCNSL patients has the advantages of safety, efficiency, and minimally invasiveness.

11.
BMC Surg ; 22(1): 398, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401240

RESUMO

BACKGROUND: Thrombotic popliteal artery aneurysm (PAA) with acute lower limb ischemia (ALI) is a serious disease leading to amputation. The choice of emergency procedures is not clearly defined, and the difference in therapeutic efficiency between open surgery and endovascular intervention is still unclear. METHOD: We conducted a comprehensive search through PubMed, Wiley Online Library and ScienceDirect. According to the predefined inclusion and exclusion criteria, eligible articles were screened out, and all relevant data were extracted for further analysis. Our study was designed and developed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guideline. We critically assessed all included articles by Joanna Briggs Institute (JBI) Critical Appraisal Checklists and the Methodological Index for Non-Randomized Studies (MINORS). RESULT: A total of 29 articles (1338 patients/1387 limbs) were included in the study. After a 1-year follow-up, the primary patency rate of the open surgery group was significantly lower than that of the endovascular intervention group (72.65 vs. 81.46%, P = 0.004), but without significant difference in the secondary patency rate (86.19 vs. 86.86%, P = 0.825). The limb salvage rate of the open surgery group was also significantly lower (83.07 vs. 98.25%, P < 0.001). After the 2-year follow-up, the primary patency rate of the open surgery group was still significantly lower (48.57 vs. 59.90%, P = 0.021). CONCLUSION: The outcome of endovascular intervention was better than that of open surgery especially in the 1-year limb salvage rate and primary patency rate at the 1-year and 2-year follow-ups.


Assuntos
Aneurisma , Procedimentos Endovasculares , Trombose , Humanos , Artéria Poplítea/cirurgia , Isquemia/etiologia , Isquemia/cirurgia , Aneurisma/complicações , Aneurisma/cirurgia , Salvamento de Membro , Trombose/complicações , Trombose/cirurgia
12.
ChemSusChem ; 15(24): e202201464, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36254787

RESUMO

Lithium-ion batteries (LIBs) are momentous energy storage devices, which have been rapidly developed due to their high energy density, long lifetime, and low self-discharge rate. However, the frequent occurrence of fire accidents in laptops, electric vehicles, and mobile phones caused by thermal runaway of the inside batteries constantly reminds us of the urgency in pursuing high-safety LIBs with high performance. To this end, this Review surveyed the state-of-the-art developments of high-temperature-resistant separators for highly safe LIBs with excellent electrochemical performance. Firstly, the basic properties of separators (e. g., thickness, porosity, pore size, wettability, mechanical strength, and thermal stability) in constructing commercialized LIBs were introduced. Secondly, the working mechanisms of advanced separators with different melting points acting in the thermal runaway stage were discussed in terms of improving battery safety. Thirdly, rational design strategies for constructing high-temperature-resistant separators for LIBs with high safety were summarized and discussed, including graft modification, blend modification, and multilayer composite modification strategies. Finally, the current obstacles and future research directions in the field of high-temperature-resistant separators were highlighted. These design ideas are expected to be applied to other types of high-temperature-resistant energy storage systems working under extreme conditions.

13.
Plant Dis ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971260

RESUMO

Tobacco is one of the most significant non-food cash crops (Lu et al. 2020). In March 2022, cigar tobacco plants showing characteristic symptoms of vascular discoloration, stem rotting, leaf wilting and rotting were observed in Tengchong city (N 25°3'26″, E 98°25'6″) of Yunnan province, China (Fig. S1). The disease incidence was about 5% on cultivar Yunxue 6 in a 33-ha field. Infected stems were collected from Tengchong for pathogen isolation and 16S rDNA sequence analysis was performed as previously described (Lu et al. 2021). Sequence analysis showed that tobacco isolates (GenBank accession numbers: ON795108, ON795107 and ON795106) had an identical sequence with that of the species type strain of Pectobacterium versatile CFBP 6051T and shared the sequence identities of 99.55% and 99.47% with P. carotovorum DSM 30168T and P. parvum s0421T, respectively. Furthermore, phylogenetic analysis showed that tobacco strains were clustered with Pectobacterium versatile CFBP 6051T (Fig. S2a). In API assays, strain 22TC1 was positive for ß-galactosidase activity, reduction of nitrates to nitrites, fermentation of glucose, hydrolysis of esculin and gelatin, assimilation of D-glucose, L-arabinose, D-mannose, D-mannitol, N-acetylglucosamine, malic acid and trisodium citrate; positive for the enzymatic substrates of alkaline phosphatase, leucine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, α-galactosidase, ß-galactosidase and α-glucosidase. Furthermore, the average nucleotide identity (ANI) analysis (Richter et al. 2015) showed that strain 22TC1 (GenBank accession number: JAMWYQ000000000) had the highest ANIb score of 96.76% and ANIm value of 97.19% with P. versatile CFBP 6051T. Similarly, in silico DNA-DNA hybridization (isDDH) value was 74.5% compared to P. versatile CFBP 6051T, isDDH values were 35.5-63.7% with the other Pectobacterium species, which below the 70% threshold value for species delineation (Meier-Kolthoff et al. 2021). The phylogenomic analysis also showed that strain 22TC1 was clustered with the species type strain of P. versatile CFBP 6051T. For pathogenicity tests, cell suspension with ten-fold dilution (approx. 1 x 108 CFU/ml) was injected into the leaf axils of two 2-month-old tobacco stems (cv. Yunyan 87). As a control, tobacco seedlings were inoculated with sterile distilled water. The plants were sealed in plastic bags and maintained in a growth chamber at 28°C for 2 d. The symptoms of water-soaked decay were observed within 24 h of inoculation. Whole-plant decay was at 2 days after injection. No symptoms were developed in the controls. Reisolation was performed on diseased stems and the identity of isolated bacteria was confirmed by PCR and sequencing of 16S rRNA. Similar results were obtained in two independent experiments. Based on the above-described data, the causal pathogen of stem rot on cigar tobacco in Tengchong was identified as P. versatile. To our knowledge, this is the first time that P. versatile is found to cause stem rot on tobacco. Pectobacterium species have been reported to cause seed-borne diseases on tobacco seedlings in the floating tray system and soil-borne diseases in tobacco fields (Wang et al. 2017; Xia and Mo 2007). Therefore, studying the possible transmission of the P. versatile to tobacco plants is necessary.

14.
BMC Bioinformatics ; 23(Suppl 4): 242, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725381

RESUMO

BACKGROUND: While it has been known that human protein kinases mediate most signal transductions in cells and their dysfunction can result in inflammatory diseases and cancers, it remains a challenge to find effective kinase inhibitor as drugs for these diseases. One major challenge is the compensatory upregulation of related kinases following some critical kinase inhibition. To circumvent the compensatory effect, it is desirable to have inhibitors that inhibit all the kinases belonging to the same family, instead of targeting only a few kinases. However, finding inhibitors that target a whole kinase family is laborious and time consuming in wet lab. RESULTS: In this paper, we present a computational approach taking advantage of interpretable deep learning models to address this challenge. Specifically, we firstly collected 9,037 inhibitor bioassay results (with 3991 active and 5046 inactive pairs) for eight kinase families (including EGFR, Jak, GSK, CLK, PIM, PKD, Akt and PKG) from the ChEMBL25 Database and the Metz Kinase Profiling Data. We generated 238 binary moiety features for each inhibitor, and used the features as input to train eight deep neural networks (DNN) models to predict whether an inhibitor is active for each kinase family. We then employed the SHapley Additive exPlanations (SHAP) to analyze the importance of each moiety feature in each classification model, identifying moieties that are in the common kinase hinge sites across the eight kinase families, as well as moieties that are specific to some kinase families. We finally validated these identified moieties using experimental crystal structures to reveal their functional importance in kinase inhibition. CONCLUSION: With the SHAP methodology, we identified two common moieties for eight kinase families, 9 EGFR-specific moieties, and 6 Akt-specific moieties, that bear functional importance in kinase inhibition. Our result suggests that SHAP has the potential to help finding effective pan-kinase family inhibitors.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Receptores ErbB , Humanos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt
15.
BMC Bioinformatics ; 23(Suppl 4): 247, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35733108

RESUMO

BACKGROUND: Human protein kinases, the key players in phosphoryl signal transduction, have been actively investigated as drug targets for complex diseases such as cancer, immune disorders, and Alzheimer's disease, with more than 60 successful drugs developed in the past 30 years. However, many of these single-kinase inhibitors show low efficacy and drug resistance has become an issue. Owing to the occurrence of highly conserved catalytic sites and shared signaling pathways within a kinase family, multi-target kinase inhibitors have attracted attention. RESULTS: To design and identify such pan-kinase family inhibitors (PKFIs), we proposed PKFI sets for eight families using 200,000 experimental bioactivity data points and applied a graph convolutional network (GCN) to build classification models. Furthermore, we identified and extracted family-sensitive (only present in a family) pre-moieties (parts of complete moieties) by utilizing a visualized explanation (i.e., where the model focuses on each input) method for deep learning, gradient-weighted class activation mapping (Grad-CAM). CONCLUSIONS: This study is the first to propose the PKFI sets, and our results point out and validate the power of GCN models in understanding the pre-moieties of PKFIs within and across different kinase families. Moreover, we highlight the discoverability of family-sensitive pre-moieties in PKFI identification and drug design.


Assuntos
Doença de Alzheimer , Neoplasias , Humanos , Proteínas Quinases/metabolismo , Transdução de Sinais
16.
World Neurosurg ; 164: e300-e306, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35500872

RESUMO

OBJECTIVE: We aim to investigate the clinical efficacy and safety of a modified hematoma puncture drainage treatment through the burr hole lateral to Kocher's point from the frontal lobe in patients with hypertensive basal ganglia hemorrhage. METHODS: Twenty-six patients were enrolled in the retrospective study. The volume of hematoma in those patients was between 25 and 35 mL, and the Glasgow Coma Scale scores were between 9 and 11; they were divided into a hematoma puncture drainage treatment group and a traditional conservative treatment group. The volume of remaining hematoma, neurological function defect scores, and life quality after treatment, duration of hospitalization, and cost of hospitalization were analyzed in these 2 groups. RESULTS: The volume of remaining hematoma was significantly less in the drainage group than that in the traditional group on the first day and the third day after treatment (P < 0.05). Posttreatment neurological function defect scores in the drainage group were statistically lower than those in the traditional group (P < 0.05). The duration of hospitalization was significantly shorter and the cost of hospitalization was also significantly less in the drainage group than that in the traditional group (P < 0.05). The Extended Glasgow Outcome Scale and Barthel Index scores were significantly higher in the drainage group than those in the traditional group (P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). CONCLUSIONS: The modified hematoma puncture drainage treatment represents an effective and safe way to treat hypertensive basal ganglia hemorrhage.


Assuntos
Hemorragia dos Gânglios da Base , Hipertensão , Hemorragia dos Gânglios da Base/complicações , Hemorragia dos Gânglios da Base/cirurgia , Drenagem , Hematoma/complicações , Hematoma/cirurgia , Humanos , Hipertensão/complicações , Punções , Estudos Retrospectivos , Resultado do Tratamento
17.
BMC Bioinformatics ; 23(Suppl 4): 130, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428180

RESUMO

BACKGROUND: Human protein kinases play important roles in cancers, are highly co-regulated by kinase families rather than a single kinase, and complementarily regulate signaling pathways. Even though there are > 100,000 protein kinase inhibitors, only 67 kinase drugs are currently approved by the Food and Drug Administration (FDA). RESULTS: In this study, we used "merged moiety-based interpretable features (MMIFs)," which merged four moiety-based compound features, including Checkmol fingerprint, PubChem fingerprint, rings in drugs, and in-house moieties as the input features for building random forest (RF) models. By using > 200,000 bioactivity test data, we classified inhibitors as kinase family inhibitors or non-inhibitors in the machine learning. The results showed that our RF models achieved good accuracy (> 0.8) for the 10 kinase families. In addition, we found kinase common and specific moieties across families using the Shapley Additive exPlanations (SHAP) approach. We also verified our results using protein kinase complex structures containing important interactions of the hinges, DFGs, or P-loops in the ATP pocket of active sites. CONCLUSIONS: In summary, we not only constructed highly accurate prediction models for predicting inhibitors of kinase families but also discovered common and specific inhibitor moieties between different kinase families, providing new opportunities for designing protein kinase inhibitors.


Assuntos
Aprendizado de Máquina , Proteínas Quinases , Humanos , Preparações Farmacêuticas , Inibidores de Proteínas Quinases/farmacologia , Estados Unidos , United States Food and Drug Administration
18.
J Clin Endocrinol Metab ; 107(6): 1589-1598, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35213704

RESUMO

CONTEXT: A few papillary thyroid microcarcinomas (PTMCs) may have skip metastasis (SLNM), but the risk factors remain controversial and the prognosis is unclear. OBJECTIVES: To investigate the incidence, lymph node metastasis (LNM) patterns, risk factors, and prognosis of SLNM in PTMCs. METHODS: We reviewed the medical records of PTMC patients who underwent thyroid surgery in our institution. Analyses of risk factors were performed for SLNM. Recurrence-free survival (RFS) of SLNM, central lymph node metastasis (CLNM), and continuous metastasis (CLNM and lateral lymph node metastasis [CLNM + LLNM]) were compared after propensity score matching (PSM). RESULTS: SLNM was detected in 1.7% (50/3923) and frequently involved level III (66.7%). Compared with CLNM + LLNM, SLNM had more LNM at a single level (P < 0.01) and less LNM at 2 levels (P < 0.05). A tumor size of 0.5 to 1 cm (odds ratio [OR], 2.26; 95% CI, 1.27-4.00) and location in the upper pole (OR, 3.30; 95% CI, 2.02-5.40) were independent risk factors for SLNM. A total of 910 (23.2%) PTMCs with LNM were included in the prognostic analysis. At a median follow-up of 60 months, the RFS of SLNM did not differ from that of CLNM (P = 0.10) but was significantly higher than that of CLNM + LLNM (P < 0.01) after using PSM. CONCLUSIONS: When the tumor size is 0.5 to 1 cm or its location is in the upper pole, we must remain vigilant to SLNM in PTMC. Because its prognosis is comparable to that of only CLNM and better than that of CLNM + LLNM, less intensive treatment should be considered.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/patologia
19.
Macromol Rapid Commun ; 43(7): e2100906, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35019170

RESUMO

Polymeric materials implanted in the human body are usually invisible under X-ray, and the mixing of heavy metal salts into polymeric materials by physical compounding often poses compatibility problems. A new iodine-containing cyclic carbonate monomer, 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide (IBTMC), is synthesized, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the side chain in the form of covalent bonds. The ring-opening polymerization of IBTMC is achieved at room temperature under the catalysis of the solid superbase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). The structure and X-ray developing ability of the synthesized polycarbonate are characterized by 1 H-NMR, X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), Gel Permeation Chromatography (GPC), and micro-computed tomography (Micro-CT). The iodine atoms remain bound to the polymer as covalent bonds after a series of reactions and exhibit a high level of X-ray opacity. In vitro degradation experiments of the polymer prove that the polymer is degradable.


Assuntos
Carbonatos , Cimento de Policarboxilato , Humanos , Cimento de Policarboxilato/química , Polimerização , Microtomografia por Raio-X
20.
ACS Nano ; 16(1): 746-754, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34985244

RESUMO

The development of flexible electronic skins with high performance and multifunctional sensing capabilities is of great significance for applications ranging from healthcare monitoring to artificial intelligence. To mimic and surpass the high-gauge-factor sensing properties of human skin, structure design and appropriate material selection of sensors are both essentially required. Here, we present an efficient, low-cost fabrication strategy to construct an ultra-highly sensitive, flexible pressure sensor by embedding the aligned nickel-coated carbon fibers (NICFs) in a polydimethylsiloxane (PDMS) substrate. Our design substantially contributes to ultrahigh sensitivity through the parallel circuit formed by aligned NICFs as well as surface spinosum microstructure molded by sandpaper. As a result, the sensor exhibits excellent sensitivity (15 525 kPa-1), a fast response time (30 ms), and good stability over 3000 loading-unloading cycles. Furthermore, these superior sensing properties trigger applications in water quality and wave monitoring in conjunction with mechanical flexibility and robustness. As a precedent for adjusting the sensitivities of the sensor, the NICFs/PDMS sensor provides a promising method for multiscenario healthcare monitoring, multiscale pressure spatial distribution, and human-machine interfacing.


Assuntos
Inteligência Artificial , Dispositivos Eletrônicos Vestíveis , Humanos , Condutividade Elétrica , Dimetilpolisiloxanos/química
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