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1.
Nanomicro Lett ; 16(1): 227, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918252

RESUMO

Ferroelectrics have great potential in the field of nonvolatile memory due to programmable polarization states by external electric field in nonvolatile manner. However, complementary metal oxide semiconductor compatibility and uniformity of ferroelectric performance after size scaling have always been two thorny issues hindering practical application of ferroelectric memory devices. The emerging ferroelectricity of wurtzite structure nitride offers opportunities to circumvent the dilemma. This review covers the mechanism of ferroelectricity and domain dynamics in ferroelectric AlScN films. The performance optimization of AlScN films grown by different techniques is summarized and their applications for memories and emerging in-memory computing are illustrated. Finally, the challenges and perspectives regarding the commercial avenue of ferroelectric AlScN are discussed.

2.
Opt Express ; 32(9): 15741-15759, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859217

RESUMO

Remotely sensed inherent optical properties (IOPs) are key proxies for synoptic mapping of primary production and carbon export in the global ocean. However, the IOPs inversion algorithms are scarcely evaluated in the Southern Ocean (SO) because of limited field observations. In this study, the performance of two widely used semi-analytical algorithms (SAAs), i.e., the quasi-analytical algorithm (QAA) and the generalized IOP model (GIOP), were evaluated using a compiled in situ bio-optical dataset in SO, as well as measurements from the Visible Infrared Imaging Radiometer Suite (VIIRS). Evaluations with in situ data show that QAA and GIOP have comparable performance in retrieving the total absorption coefficient (a(λ)), absorption coefficients of phytoplankton (aph(λ)), and that of detritus and colored dissolved organic matter (adg(λ)). Overall, it was found that remotely sensed a(λ) and aph(λ) by both SAAs agreed well with field measurements, with the mean absolute percentage difference (MAPD) of derived a(λ) and aph(λ) in the blue-green bands being ∼20% and ∼40%, respectively. However, derived adg(λ) by both SAAs were higher than the measured values at the lower end (adg(443) < ∼0.01 m-1), but lower at the higher end (adg(443) > ∼0.02 m-1), with MAPD of ∼60%. Results of this effort suggest confident products of a(λ) and aph(λ) from VIIRS in SO, but more dedicated efforts on the measurements and evaluation of adg(λ) in SO would be desired.

3.
Nat Prod Res ; : 1-7, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752778

RESUMO

The fungus Penicillium egyptacum has been reported as a producer of the 16-membered macrolide antibiotic A26771B. In this study, two new berkeleylactone analogues, berkeleylactones S-T (1-2), were isolated from P. egyptiacum. Their structures were determined by the analyses of 1D- and 2D-NMR data, HRESIMS, and chemical derivatization. 1 is the first example of berkeleylactone analogue possessing a glucose moiety, whose absolute configuration was elucidated by acid hydrolysis followed by derivatization and LC-MS analysis. No antibacterial activity against Bacillus subtilis and Streptococcus salivarius was found within the range of 0-100 µM for compounds 1-2.

4.
Biophys J ; 123(7): 839-846, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38419331

RESUMO

Ras proteins are important intracellular signaling hubs that can interact with numerous downstream effectors and upstream regulators through their GTPase domains (G-domains) anchored to plasma membranes by the C-terminal hypervariable regions (HVRs). The biological functions of Ras were proposed to be regulated at multiple levels including the intramolecular G-domain-HVR interactions, of which the exact mechanism and specificity are still controversial. Here, we demonstrate that the HVRs, instead of having direct contacts, can weakly perturb the G-domains via an allosteric interaction that is restricted to a ∼20 Å range and highly conserved in the tested Ras isoforms (HRas and KRas4B) and nucleotide-bound states. The origin of this allosteric perturbation has been localized to a short segment (residues 167-171) coinciding with region 1 of HVRs, which exhibits moderate to weak α-helical propensities. A charge-reversal mutation (E168K) of KRas4B in region 1, previously described in the Catalog of Somatic Mutations in Cancer database, was found to induce similar chemical shift perturbations as truncation of the HVR does. Further membrane paramagnetic relaxation enhancement (mPRE) data show that this region 1 mutation alters the membrane orientations of KRas4B and moderately increases the relative population of the signaling-compatible state.


Assuntos
Transdução de Sinais , Proteínas ras , Isoformas de Proteínas/química , Membrana Celular/metabolismo , Mutação , Proteínas ras/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
5.
Sci Rep ; 14(1): 3670, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351185

RESUMO

Clamping bushing structure is an internode connection mechanism designed for the standard section of tubular truss tower. In this paper, the clamping bushing structure of the connecting mechanism of super-large tower crane is taken as the research object, a three-dimensional model of clamping bushing structure is established and imported into ABAQUS, and its multi-body contact model is further constructed to study the contact and bearing relationship of the structure under multiple working conditions, and the accuracy of the calculation results of the model is verified by the experimental stress test under tensile working conditions. In addition, this study is based on the control variable method, and through the design of orthogonal test table, the influence degree of five variable parameters of clamping bushing on the bearing capacity of the structure is investigated. Finally, through the range analysis, the optimal horizontal combination of variables and parameters of clamping bushing structure is obtained, and the optimal matching relationship between the shape of the tower connecting mechanism and the bearing capacity is obtained. The results show that, compared with the original model, the stress concentration at the most dangerous section of the optimized joint and the bushing is obviously alleviated, in which the stress peaks of the upper and lower joints are kept below 500 MPa, and the stress peaks of the bushing groove are also reduced to between 573 and 722 MPa. Moreover, the designed and optimized lower joint can reduce the maximum equivalent plastic strain of the joint root circumference by 56.05% under the original maximum tensile condition, and the overall distribution trend of equivalent plastic strain is more uniform, and a more reliable structural design is obtained, which plays an important guiding role in the design, optimization and analysis of the connecting mechanism of the tower body of large tower crane.

6.
Dig Endosc ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173187

RESUMO

OBJECTIVES: Modified endoscopic retrograde appendicitis therapy (mERAT) has been proposed as an alternative to laparoscopic appendectomy for the treatment of appendicitis. However, data from children in large samples are lacking. The aim of this article is to evaluate the efficacy between mERAT and laparoscopic appendectomy (LA) in children with uncomplicated appendicitis. METHOD: We retrospectively analyzed 594 patients with suspected uncomplicated appendicitis from October 2018 to May 2021. A pool of 294 consecutive patients who met the inclusion criteria were ultimately enrolled in this study (228 and 66 patients in mERAT and LA, respectively). Given the differences in baseline clinical data (gender, age), the regression equation including differences in clinical baseline, grouping factor, and white blood cell count was established to address the influence of potential confounding factors. RESULT: The initial success rate of mERAT management was 96.9%, and the recurrence rate was 6.9% in the mERAT group and 1.7% in the LA group within 1 year, which was no significant difference. But the mERAT group had a lower rate of adverse events. Finally, those results indicated that the treatment modalities, LA or mERAT, had no significant effect on initial success rate (P = 0.99) or recurrence rate (P = 0.17) within 1 year, but a significant effect on the adverse events rate during hospitalization (P = 0.01) in the multivariate regression analysis. CONCLUSION: Among children with uncomplicated appendicitis, an initial mERAT management strategy had a success rate of 96.9%, which was similar to the LA group at 1 year. This follow-up supports the feasibility of mERAT alone as an alternative to surgery for uncomplicated appendicitis.

7.
Transpl Immunol ; 82: 101961, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184216

RESUMO

BACKGROUND: The kidney donor profile index (KDPI) evaluates kidney donor's age, height, weight, ethnicity, cause of death, high blood pressure, diabetes, exposure to hepatitis C and estimated glomerular filtration (eGFR). Kidneys with lower KDPI scores are expected to function longer that those with higher KPDI values. The applicability of KDPI score in Chinese kidney transplant donation has not yet been validated. This study evaluated the prognostic value of KDPI score in Chinese kidney transplant patients. METHODS: A retrospective analysis was conducted on 184 deceased donors and 353 corresponding kidney transplant patients at the Organ Transplantation Department of Renmin Hospital of Wuhan University between 2018 and 2021. The donors and recipients were stratified into four groups based on their KDPI score: KDPI 85-100, KDPI 60-84, KDPI 21-59, and KDPI 0-20. RESULTS: As expected, the KDPI 85-100 group was associated with a poor short-term renal function (both postoperative creatinine and eGFR with P > 0.05), a higher incidence of delayed graft function (DGF; 25.5% for KDPI 85-100 group vs. 10.2% for KDPI 60-84 group vs. 5.4% for KDPI 21-59 group vs. 0 for KDPI 0-20 group, all P > 0.05). Furthermore, the same groups showed worse 3-year patient survival rate: 86.3% for KDPI 85-100 group vs. 97.01% for KDPI 60-84 group vs. 97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05); and renal survival rate: 82.6% for KDPI 85-100 group vs. 92.99% KDPI 60-84 group vs.97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05). Our analysis showed that the KDPI score had a good predictive value for the survival of kidney transplants and patients in our center (area under the curve: 0.728 and 0.76, P > 0.05). CONCLUSION: We recommend that the KDPI scoring system can be employed as an effective tool to predict kidney transplantation outcomes in deceased donation in China.


Assuntos
Transplante de Rim , Humanos , Estudos Retrospectivos , Sobrevivência de Enxerto , Doadores de Tecidos , Rim , Fatores de Risco
8.
J Asian Nat Prod Res ; 26(1): 139-145, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38050667

RESUMO

Four new 2-pyrone derivatives, two pairs of enantiomers, (±)-egypyrone A [(±)-1] and (±)-egypyrone B [(±)-2], together with a new benzophenone analogue, orbiophenone B (3), were isolated from the endophytic fungus Penicillium egyptiacum. The enantiomeric mixtures (±)-1 and (±)-2 were separated through chiral HPLC, respectively. Their structures were elucidated by extensive analysis of spectroscopic data and the absolute configuration was determined by comparing the optical rotation of structurally similar molecule. Subsequently, the cytotoxic activities of (±)-1, (±)-2, and 3 against the U87 cell line were tested and no activity was observed at a concentration of 10 µM.


Assuntos
Penicillium , Penicillium/química , Fungos , Pironas/química , Estrutura Molecular
9.
J Am Chem Soc ; 145(46): 25080-25085, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37948671

RESUMO

Comparison of biosynthetic gene clusters (BGCs) found in devastating plant pathogens and biocontrol fungi revealed an uncharacterized and conserved polyketide BGC. Genome mining identified the associated metabolite to be treconorin, which has a terpene-like, trans-fused 5,7-bicyclic core that is proposed to derive from a (4 + 3) cycloaddition. The core is esterified with d-glucose, which derives from the glycosidic cleavage of a trehalose ester precursor. This glycomodification strategy is different from the commonly observed glycosylation of natural products.


Assuntos
Policetídeos , Terpenos , Família Multigênica , Fungos/genética
10.
Aging (Albany NY) ; 15(17): 8930-8947, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37688769

RESUMO

Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells, thus forming a special immune microenvironment, which plays a key role in the occurrence and development of hepatocellular carcinoma. Nowadays, tumor immunotherapy has become one of the most promising cancer treatment methods. Immune checkpoint inhibitors (ICIs) combined with VEGF inhibitors are listed as first-line treatment options for advanced HCC. Therefore, the search for a potential biomarker to predict the response to immunotherapy in HCC patients is urgently needed. The G protein-coupled receptor 55 (GPR55), a lysophosphatidylinositol (LPI) receptor, has recently emerged as a potential new target for anti-tumor therapy. Previous studies have found that GPR55 is highly expressed in breast cancer, pancreatic cancer, skin cancer and cholangiocarcinoma, and is involved in tumor proliferation and migration. However, the role and mechanism of GPR55 in HCC has not been elucidated. Therefore, this article discusses the clinical significance of GPR55 in HCC and its correlation with the immune response of HCC patients, so as to provide theoretical basis for improving the prognosis of HCC.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Prognóstico , Ductos Biliares Intra-Hepáticos , Microambiente Tumoral , Receptores de Canabinoides
11.
Diagnostics (Basel) ; 13(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685276

RESUMO

BACKGROUND: The objective of this study was to formulate and validate a prognostic model for postoperative severe Pneumocystis carinii pneumonia (SPCP) in kidney transplant recipients utilizing machine learning algorithms, and to compare the performance of various models. METHODS: Clinical manifestations and laboratory test results upon admission were gathered as variables for 88 patients who experienced PCP following kidney transplantation. The most discriminative variables were identified, and subsequently, Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbor (KNN), Light Gradient Boosting Machine (LGBM), and eXtreme Gradient Boosting (XGB) models were constructed. Finally, the models' predictive capabilities were assessed through ROC curves, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1-scores. The Shapley additive explanations (SHAP) algorithm was employed to elucidate the contributions of the most effective model's variables. RESULTS: Through lasso regression, five features-hemoglobin (Hb), Procalcitonin (PCT), C-reactive protein (CRP), progressive dyspnea, and Albumin (ALB)-were identified, and six machine learning models were developed using these variables after evaluating their correlation and multicollinearity. In the validation cohort, the RF model demonstrated the highest AUC (0.920 (0.810-1.000), F1-Score (0.8), accuracy (0.885), sensitivity (0.818), PPV (0.667), and NPV (0.913) among the six models, while the XGB and KNN models exhibited the highest specificity (0.909) among the six models. Notably, CRP exerted a significant influence on the models, as revealed by SHAP and feature importance rankings. CONCLUSIONS: Machine learning algorithms offer a viable approach for constructing prognostic models to predict the development of severe disease following PCP in kidney transplant recipients, with potential practical applications.

12.
ACS Omega ; 8(31): 28821-28833, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37576696

RESUMO

The high adsorption capacity of coal reservoirs poses a challenge to the evaluation of productivity and output profiles for each segment of fractured horizontal wells using tracers. In this study, the microstructure of a coal sample from block B and its absorption character to a micromaterial tracer are analyzed first. Then, an anti-adsorption micromaterial tracer system which is suitable for block B is proposed by evaluating different types of complexing agents and extractant agents. The system comprises micromaterial tracers (200 ppb) + ethylenediaminetetraacetic acid tetrasodium (EDTA-4Na in short) (0.01%) + di(2-ethylhexyl) phosphate (HDEHP in short) (0.001%), and its anti-adsorption character of the system is analyzed. The concentration dynamics of micromaterial tracers are analyzed by the flowback fluid testing of one fracturing well and two adjacent wells. Then, a judging method for productivity and connectivity of each segment of horizontal wells is established. Moreover, the anti-adsorption micromaterial tracer system judgment method is employed to analyze the staged fracturing performance of horizontal well B1 in the coal reservoir of block B. Eight types of micromaterial tracers are utilized to label the fluid in each fracturing segment for assessing the connectivity between well B1 and adjacent wells B1-1 and B1-2. The results show that the anti-adsorption micromaterial tracer system exhibits minimal adsorption loss and can be well applied in segment monitoring in the horizontal fracturing well of coal reservoirs. The main productive segments of well B1 are #1, #4, and #8. Well B1 exhibits good connectivity with adjacent well B1-1 in segments #1, #4, #6, and #8. Conversely, all segments of well B1 exhibit poor connectivity with adjacent well B1-2. The results can provide a dependable reference for optimizing fracturing parameters, well spacing, and productivity evaluation in coal reservoirs. The results obtained in this study are consistent with the results obtained by using the four-dimensional (4D in short) image monitoring technology, which proves the good accuracy and reliability of the micromaterial tracer monitoring method.

13.
Front Med (Lausanne) ; 10: 1181743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37502357

RESUMO

Background: BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention. Methods: Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia. Results: During a median follow-up time of 1,072 days (range 739-1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5-10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia. Conclusion: The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.

14.
Front Immunol ; 14: 1167667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304282

RESUMO

Background and aims: In the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury. Methods and results: We systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1. Conclusion: Our findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.


Assuntos
MAP Quinase Quinase Quinases , Traumatismo por Reperfusão , Animais , Camundongos , Fígado , MAP Quinase Quinase Quinases/genética , Camundongos Knockout , Camundongos Transgênicos , Traumatismo por Reperfusão/genética , Proteases Específicas de Ubiquitina/genética
15.
J Inflamm Res ; 16: 1405-1418, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37012971

RESUMO

The mitogen-activated protein kinase signaling pathway can be activated by a variety of growth factors, cytokines, and hormones, and mediates numerous intracellular signals related to cellular activities, including cell proliferation, motility, and differentiation. It has been widely studied in the occurrence and development of inflammation and tumor. Hepatic ischemia-reperfusion injury (HIRI) is a common pathophysiological phenomenon that occurs in surgical procedures such as lobectomy and liver transplantation, which is characterized by severe inflammatory reaction after ischemia and reperfusion. In this review, we mainly discuss the role of p38, ERK1/2, JNK in MAPK family and TAK1 and ASK1 in MAPKKK family in HIRI, and try to find an effective treatment for HIRI.

16.
Transpl Immunol ; 78: 101828, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36948406

RESUMO

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and the most common hereditary disease leading to end-stage renal disease in children and adolescents. The NPHP1 gene was the first NPHP gene to be discovered. Pathogenic variation of the NPHP1 gene can cause juvenile renal wasting disease type 1. CASE PRESENTATION: Here, we report the first case of living related kidney transplantation of monozygotic twins with NPHP1 nephronophthisis in China; one of these cases involved cross-blood type kidney transplantation. Our experience shows that patients with NPHP1 nephronophthisis have almost no risk recurrent kidney disease following living related kidney transplantation and genetic testing. The two twins recovered well without any complications. CONCLUSIONS: This is the first report of living related kidney transplantation of monozygotic twins with heterozygous deletion of the NPHP1 gene in a Chinese family with NPHP. In addition, genetic testing provides an efficient means of evaluating the safety of living related kidney transplantation in patients with NPHP1 nephronophthisis.


Assuntos
Transplante de Rim , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , População do Leste Asiático , Homozigoto , Doadores Vivos , Proteínas de Membrana/genética , Deleção de Sequência , Gêmeos Monozigóticos
17.
Heliyon ; 9(3): e13855, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36895342

RESUMO

Fe-Al-Cr coatings with different content of Cr additive were prepared on 1045 carbon steel substrates by a laser cladding process. The incorporation of Cr atoms can effectively enhance the corrosion resistance of the coatings. In particular, the Fe-28Al-5Cr laser cladding coating exhibits the best film quality without phase segregation. In addition, the interfacial adhesion between the Fe-28Al-5Cr coating and the 1045 carbon steel substrate is improved. As a result, the Fe-28Al-5Cr laser cladding coating exhibits the best corrosion resistance in a 3.5 wt% NaCl solution under both immersion and electrochemical conditions. However, excessive Cr additive lead to the formation of Al8Cr5 in the grain boundaries, resulting in inferior corrosion resistance. Therefore, the new findings demonstrated in this work may inspire the design of high-quality coatings with excellent corrosion resistance.

18.
J Am Chem Soc ; 145(12): 6643-6647, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36920241

RESUMO

The complete biosynthetic pathways of the potent antifungals AS2077715 (1) and funiculosin (2) are reconstituted and characterized. A five-enzyme cascade, including a multifunctional flavin-dependent monooxygenease and a repurposed O-methyltransferase, is involved to perform the dearomatization, stereoselective ring contraction, and redox transformations to morph a hydroxyphenyl-containing precursor into the unusual all-cis cyclopentanetetraol moiety.


Assuntos
Antifúngicos , Oxirredução
19.
J Chemother ; 35(3): 181-187, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35815561

RESUMO

Echinocandins form a new drug class for the treatment of Pneumocystis pneumonia (PCP), but their efficacies have not been confirmed. The objective of this study was to review the all-cause mortality and efficacy of echinocandins combined with trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of PCP. A meta-analysis of retrospective case-control studies of echinocandins combined with TMP/SMZ or TMP/SMZ alone for treating adult PCP was performed. Pubmed, Web of Sciences, Cochrane Register of Controlled Trials, and Embase databases were searched from inception to October 20, 2021. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a fixed effects model in the meta-analysis to derive pooled estimates of effect size. Five-hundred forty articles were identified and screened, and five studies were included meta-analysis. Echinocandins combined with TMP/SMZ led to a reduction in all-cause mortality of pneumocystis pneumonia (OR = 0.47; 95%CI 0.32-0.71; P = 0.0003), and the total positive response rate of echinocandins combined with TMP/SMZ was higher than that of TMP/SMZ (OR = 2.16; 95%CI 1.46-3.19; P = 0.0001). This meta-analysis based on retrospective case-control studies was first to show that echinocandins combined with TMP/SMZ for the treatment of pneumocystis pneumonia can lead to a reduction in mortality and improvement in treatment response rates. It is suggested that echinocandins may be a good drug for treating PCP.


Assuntos
Equinocandinas , Pneumonia por Pneumocystis , Adulto , Humanos , Equinocandinas/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
20.
Environ Toxicol ; 37(10): 2375-2387, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35785413

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with slow onset and high mortality. Epithelial-mesenchymal transition (EMT) is a significant condition for tissue fibrosis, and lncRNA-Snhg6 (small nucleolar RNA host gene 6) is related to EMT in some cancer cells, but its role in pulmonary fibrosis remains obscure. Here, we found that TGF-ß1 and Snhg6 were up-regulated in lung tissues of BLM-induced lung fibrosis mouse, and Snhg6 expression was significantly increased in primary lung fibroblasts after BLM treatment. Snhg6 knockdown notably alleviated the pulmonary dysfunction, and the increase of fibrosis area and collagen deposition induced by BLM. MiR-26a-5p was downregulated in BLM-induced fibrotic lung tissues, and it was negatively regulated by Snhg6. Silencing Snhg6 markedly alleviated the TGF-ß1-induced increase in fibrotic marker expression, cell proliferation, migration and differentiation, as well as the nuclear transport of p-Smad2/3 by modulating miR-26a-5p expression in mouse lung fibroblasts. Moreover, overexpressing Snhg6-induced collagen accumulation and fibroblast activation in fibroblasts, which was reversed by treatment with miR-26a-5p mimic or oxymatrine (an inhibitor of TGF-ß1-Smads pathway). Interestingly, silencing Snhg6 in vivo mitigated BLM-driven pulmonary fibrosis by regulating the miR-26a-5p/TGF-ß1-Smads axis. Our data revealed that Snhg6 contributed to the process of BLM-driven lung fibrosis in mouse by modulating the miR-26a-5p/TGF-ß1-Smads axis, suggesting that Snhg6 might be a therapeutic target for lung fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , MicroRNAs , RNA Longo não Codificante , Animais , Bleomicina/toxicidade , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
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