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1.
FASEB J ; 38(11): e23697, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38842874

RESUMO

Diabetic retinopathy (DR) is characterized by chronic, low-grade inflammation. This state may be related to the heightened production of neutrophil extracellular traps (NETs) induced by high glucose (HG). Human cathelicidin antimicrobial peptide (LL37) is an endogenous ligand of G protein-coupled chemoattractant receptor formyl peptide receptor 2 (FPR2), expressed on neutrophils and facilitating the formation and stabilization of the structure of NETs. In this study, we detected neutrophils cultured under different conditions, the retinal tissue of diabetic mice, and fibrovascular epiretinal membranes (FVM) samples of patients with proliferative diabetic retinopathy (PDR) to explore the regulating effect of LL37/FPR2 on neutrophil in the development of NETs during the process of DR. Specifically, HG or NG with LL37 upregulates the expression of FPR2 in neutrophils, induces the opening of mitochondrial permeability transition pore (mPTP), promotes the increase of reactive oxygen species and mitochondrial ROS, and then leads to the rise of NET production, which is mainly manifested by the release of DNA reticular structure and the increased expression of NETs-related markers. The PI3K/AKT signaling pathway was activated in neutrophils, and the phosphorylation level was enhanced by FPR2 agonists in vitro. In vivo, increased expression of NETs markers was detected in the retina of diabetic mice and in FVM, vitreous fluid, and serum of PDR patients. Transgenic FPR2 deletion led to decreased NETs in the retina of diabetic mice. Furthermore, in vitro, inhibition of the LL37/FPR2/mPTP axis and PI3K/AKT signaling pathway decreased NET production induced by high glucose. These results suggested that FPR2 plays an essential role in regulating the production of NETs induced by HG, thus may be considered as one of the potential therapeutic targets.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Catelicidinas , Retinopatia Diabética , Armadilhas Extracelulares , Camundongos Endogâmicos C57BL , Neutrófilos , Receptores de Formil Peptídeo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Armadilhas Extracelulares/metabolismo , Animais , Receptores de Formil Peptídeo/metabolismo , Receptores de Formil Peptídeo/genética , Humanos , Neutrófilos/metabolismo , Camundongos , Peptídeos Catiônicos Antimicrobianos/metabolismo , Masculino , Receptores de Lipoxinas/metabolismo , Receptores de Lipoxinas/genética , Diabetes Mellitus Experimental/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Feminino , Pessoa de Meia-Idade
2.
Kaohsiung J Med Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38820598

RESUMO

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/ß-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/ß-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed ß-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

3.
Quant Imaging Med Surg ; 14(5): 3655-3664, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38720833

RESUMO

Background: Although previous studies have shown that the injection of contrast agents can improve image quality, the specific impact of this on T2-weighted fat-suppressed (T2 FS) and diffusion-weighted imaging (DWI) sequences in the diagnosis of breast cancer remains incompletely understood. In particular, there is insufficient research on how contrast agents affect the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values within these sequences, and how these changes influence the diagnosis of benign and malignant breast tumors. Methods: Breast magnetic resonance images (MRI) were obtained from 178 consecutive patients on a 3T scanner. The SNR and CNR of lesions on T2 FS sequence were calculated before and after contrast agent injection and compared. Differences between pre- and post-contrast ADC in identifying different tumor types were compared using the Kruskal-Wallis H-test and the paired comparison test. The accuracy of ADC values between pre- and post-contrast in distinguishing benign and malignant breast masses was assessed using receiver operating characteristic (ROC) curves. Results: The SNR and CNR of T2 FS sequence increased after contrast injection, and especially for invasive cancer and benign tumor, the increase was significant. For DWI, there was a slight increase or decrease of ADC values after contrast injection, but the ADC values before and after contrast had a similar effect in identifying different types of tumors. In the ROC curve analysis for assessing benign and malignant breast tumors, the area under the curve (AUC) before and after contrast showed similar results. Conclusions: Contrast agent injection can improve the SNR and CNR of T2 FS sequence, thus providing higher quality images for the diagnosis of breast lesions. Furthermore, injection of contrast agent had little effect on the ability of ADC values to identify different types of lesions and both ADC values before and after the contrast agent were able to distinguish between benign and malignant tumors with almost the same accuracy.

4.
Nutrients ; 16(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732513

RESUMO

Modulating the gut microbiota is recognised as one strategy for preventing and fighting diseases. While the significant impact of diet on the gut microbiota's composition and function has been extensively researched, there is a notable lack of studies on the interactions between diet, microbiota, and helminth infections. Here, we used a combination of self-reported food intake and a 16S rDNA sequencing approach to analyse the composition of the gut microbiota in women of reproductive age from the two main islands of the Zanzibar archipelago, where helminth infections are endemic. We also applied a Spearman correlation analysis to food/nutrients and gut microbiota. Our results reveal that, despite close ethnic and cultural ties, the participants' gut microbiota differs depending on their location. A nutrient intake analysis revealed deficiencies in minerals and vitamins, indicating an imbalanced diet. A correlation analysis identified bacterial taxa consistently correlated with specific food or nutrients in healthy women from both locations, and in two types of helminth infections. Escherichia/Shigella abundances, usually associated with Trichuris trichiura infection, consistently correlated with insufficient levels of vitamins B2 and B12. In conclusion, our findings suggest that the increased consumption of specific food like cassava and fish, as well as essential nutrients such as calcium, B vitamins, and vitamin A, may modulate the gut microbiota of populations residing in regions where helminth infections are endemic.


Assuntos
Dieta , Microbioma Gastrointestinal , Helmintíase , Humanos , Tanzânia , Feminino , Adulto , Helmintíase/epidemiologia , Nutrientes , Adulto Jovem , Adolescente , Fezes/microbiologia , RNA Ribossômico 16S , Animais , Bactérias/classificação , Bactérias/genética
5.
Nat Commun ; 15(1): 3721, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698059

RESUMO

The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.

6.
Sci Rep ; 14(1): 9208, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649431

RESUMO

This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer. Female patients ≤ 80 years old with unilateral T1-T4 invasive ductal breast cancer treated with neoadjuvant chemotherapy (NAC) and radiation therapy (RT) between 2006 and 2015 were enrolled from SEER database. Baseline differences in clinical and pathological characteristics were evaluated using chi-square test. The survival outcomes were estimated by Kaplan-Meier analysis and compared using Cox hazards models. The effects of baseline differences on survival outcome in patients treated with neoadjuvant radiation therapy (NART) and post-operation radiation therapy (PORT) were circumvented by propensity score matching (PSM). Altogether 14,151 patients receiving NAC and RT were enrolled, among whom 386 underwent NART. Based on a 1:4 PSM cohort, NART was an independent unfavorable prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) for the whole cohort. However, among patients receiving breast conserving surgery (BCS) (HR 1.029, P = 0.915 for BCSS; HR 1.003, P = 0.990 for OS) or implant-based immediate breast reconstruction (IBR) (HR 1.039, P = 0.921 for BCSS; HR 1.153, P = 0.697 for OS), those treated with NART had similar survival outcomes compared with patients treated with PORT. In conclusion, NARCT was a safe and feasible approach for patients undergoing BCS and IBR.


Assuntos
Neoplasias da Mama , Mastectomia Segmentar , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Idoso , Adulto , Mamoplastia/métodos , Estimativa de Kaplan-Meier , Resultado do Tratamento , Quimiorradioterapia/métodos , Idoso de 80 Anos ou mais , Prognóstico , Estudos Retrospectivos
7.
Environ Res ; 252(Pt 3): 118941, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38649015

RESUMO

The Zn/Zr-MOFs were synthesized via microwave-assisted ball milling and subsequently characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The thermal stability of the Zn/Zr-MOFs was evaluated through thermogravimetry (TGA). The results demonstrated the exceptional adsorption properties of the Zn/Zr-MOFs towards Lomefloxacin hydrochloride and Levofloxacin hydrochloride. At a concentration of 30 ppm for Lomefloxacin hydrochloride, the addition of 30 mg of Zn/Zr-MOFs material resulted in an adsorption capacity of 179.2 mg•g-1. Similarly, at a concentration of 40 ppm for Levofloxacin hydrochloride, the addition of 30 mg Zn/Zr-MOFs material led to an adsorption capacity of 187.1 mg•g-1. Kinetic analysis revealed that the experimental data aligned well with a pseudo-second order kinetic model. Overall, these findings highlight the significant potential application of Zn/Zr-MOF materials in wastewater treatment.


Assuntos
Fluoroquinolonas , Levofloxacino , Micro-Ondas , Águas Residuárias , Poluentes Químicos da Água , Zinco , Levofloxacino/química , Adsorção , Fluoroquinolonas/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Zinco/química , Águas Residuárias/química , Zircônio/química , Antibacterianos/química , Cinética , Estruturas Metalorgânicas/química
8.
BMC Infect Dis ; 24(1): 405, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622501

RESUMO

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.


Assuntos
Infecções por Chlamydia , Infertilidade , Humanos , Feminino , Chlamydia trachomatis/genética , Estudos Soroepidemiológicos , Infertilidade/epidemiologia , Infertilidade/complicações , Infecções por Chlamydia/diagnóstico , DNA , Genitália
9.
Front Public Health ; 12: 1333559, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476494

RESUMO

Introduction: Among the different antigens used in the detection of anti-Chlamydia trachomatis antibodies, significant differences in sensitivity and specificity have been observed. Further evaluation of C. trachomatis antigens in antibody detection is urgently needed for the development and application of C. trachomatis serologic assays. Methods: Chlamydia trachomatis antigens Pgp3, TmeA, InaC, and HSP60 were selected and used in luciferase immunosorbent assay (LISA). The detection results obtained from well-defined C. trachomatis positive and negative samples were compared with the commercial C. trachomatis ELISA (Mikrogen) for performance evaluation. Results: Pgp3, TmeA, InaC, and HSP60-based LISA showed sensitivity of 92.8, 88.8, 90.4, and 94.4%, and specificity of 99.2, 99.2, 99.2, and 92%, respectively. ROC analysis indicated that Pgp3-based LISA showed similar performance to Mikrogen ELISA (AUC 0.986 vs. 0.993, p = 0.207). Furthermore, four C. trachomatis antigens achieved strong diagnostic efficiency, i.e., positive likelihood ratios [+LR] ≥ 10 in C. trachomatis-infected women and negative likelihood ratios [-LR] ≤ 0.1 in C. trachomatis negative low exposure risk children, but only Pgp3 and TmeA showed strong diagnostic value in general adults. In addition, Pgp3, TmeA, and InaC, but not HSP60, achieved high performance, i.e., both positive predictive value (PPV) and negative predictive value (NPV) ≥ 90.9%, and showed no significant cross-reactivity with anti-Chlamydiapneumoniae. Conclusion: Three C. trachomatis species-specific antigens Pgp3, TmeA, and InaC show superior performance in the detection of anti-C. trachomatis antibody, indicating the potential to be used in developing C. trachomatis serologic tests.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Adulto , Criança , Feminino , Humanos , Imunoadsorventes , Infecções por Chlamydia/diagnóstico , Antígenos de Bactérias , Ensaio de Imunoadsorção Enzimática/métodos
10.
Virulence ; 15(1): 2322961, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38443331

RESUMO

Gram-negative Bartonella species are facultative intracellular bacteria that can survive in the harsh intracellular milieu of host cells. They have evolved strategies to evade detection and degradation by the host immune system, which ensures their proliferation in the host. Following infection, Bartonella alters the initial immunogenic surface-exposed proteins to evade immune recognition via antigen or phase variation. The diverse lipopolysaccharide structures of certain Bartonella species allow them to escape recognition by the host pattern recognition receptors. Additionally, the survival of mature erythrocytes and their resistance to lysosomal fusion further complicate the immune clearance of this species. Certain Bartonella species also evade immune attacks by producing biofilms and anti-inflammatory cytokines and decreasing endothelial cell apoptosis. Overall, these factors create a challenging landscape for the host immune system to rapidly and effectively eradicate the Bartonella species, thereby facilitating the persistence of Bartonella infections and creating a substantial obstacle for therapeutic interventions. This review focuses on the effects of three human-specific Bartonella species, particularly their mechanisms of host invasion and immune escape, to gain new perspectives in the development of effective diagnostic tools, prophylactic measures, and treatment options for Bartonella infections.


Assuntos
Infecções por Bartonella , Bartonella , Humanos , Evasão da Resposta Imune , Apoptose , Biofilmes , Proteínas de Membrana
11.
Clin Epigenetics ; 16(1): 33, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414041

RESUMO

BACKGROUND: Whole-genome methylation sequencing of cfDNA is not cost-effective for tumor detection. Here, we introduce reduced representative methylome profiling (RRMP), which employs restriction enzyme for depletion of AT-rich sequence to achieve enrichment and deep sequencing of CG-rich sequences. METHODS: We first verified the ability of RRMP to enrich CG-rich sequences using tumor cell genomic DNA and analyzed differential methylation regions between tumor cells and normal whole blood cells. We then analyzed cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals to detect breast cancer by building machine learning models. RESULTS: RRMP captured 81.9% CpG islands and 75.2% gene promoters when sequenced to 10 billion base pairs, with an enrichment efficiency being comparable to RRBS. RRMP allowed us to assess DNA methylation changes between tumor cells and whole blood cells. Applying our approach to cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals, we developed machine learning models that could discriminate between breast cancer and non-breast cancer controls (AUC = 0.85), suggesting possibilities for truly non-invasive cancer detection. CONCLUSIONS: We developed a new method to achieve reduced representative methylome profiling of cell-free DNA for tumor detection.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Humanos , Feminino , Metilação de DNA , Epigenoma , Ácidos Nucleicos Livres/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ilhas de CpG
12.
Microbiol Spectr ; 12(3): e0364523, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38319081

RESUMO

CRISPR-Cas technology has widely been applied to detect single-nucleotide mutation and is considered as the next generation of molecular diagnostics. We previously reported the combination of nucleic acid amplification (NAA) and CRISPR-Cas12a system to distinguish major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the mixture of NAA and CRISPR-Cas12a reagents in one tube could interfere with the efficiency of NAA and CRISPR-Cas12a cleavage, which in turn affects the detection sensitivity. In the current study, we employed a novel photoactivated CRISPR-Cas12a strategy integrated with recombinase polymerase amplification (RPA) to develop one-pot RPA/CRISPR-Cas12a genotyping assay for detecting SARS-CoV-2 Omicron sub-lineages. The new system overcomes the potential inhibition of RPA due to early CRISPR-Cas12a activation and cleavage of the target template in traditional one-pot assay using photocleavable p-RNA, a complementary single-stranded RNA to specifically bind crRNA and precisely block Cas12a activation. The detection can be finished in one tube at 39℃ within 1 h and exhibits a low limit of detection of 30 copies per reaction. Our results demonstrated that the photocontrolled one-pot RPA/CRISPR-Cas12a assay could effectively identify three signature mutations in the spike gene of SARS-CoV-2 Omicron variant, namely, R346T, F486V, and 49X, and distinguish Omicron BA.1, BA.5.2, and BF.7 sub-lineages. Furthermore, the assay achieved a sensitivity of 97.3% and a specificity of 100.0% and showed a concordance of 98.3% with Sanger sequencing results.IMPORTANCEWe successfully developed one-pot recombinase polymerase amplification/CRISPR-Cas12a genotyping assay by adapting photocontrolled CRISPR-Cas technology to optimize the conditions of nucleic acid amplification and CRISPR-Cas12a-mediated detection. This innovative approach was able to quickly distinguish severe acute respiratory syndrome coronavirus 2 Omicron variants and can be readily modified for detecting any nucleic acid mutations. The assay system demonstrates excellent clinical performance, including rapid detection, user-friendly operations, and minimized risk of contamination, which highlights its promising potential as a point-of-care testing for wide applications in resource-limiting settings.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , COVID-19/diagnóstico , Sistemas CRISPR-Cas , SARS-CoV-2/genética , Recombinases , RNA
13.
Nano Lett ; 24(2): 733-740, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38166427

RESUMO

The Hall effect has played a vital role in unraveling the intricate properties of electron transport in solid materials. Here, we report on a crystal symmetry-dependent in-plane Hall effect (CIHE) observed in a CuPt/CoPt ferromagnetic heterostructure. Unlike the planar Hall effect (PHE), the CIHE in CuPt/CoPt strongly depends on the current flowing direction (ϕI) with respect to the crystal structure. It reaches its maximum when the current is applied along the low crystal-symmetry axes and vanishes when applied along the high crystal-symmetry axes, exhibiting an unconventional angular dependence of cos(3ϕI). Utilizing a symmetry analysis based on the Invariant Theory, we demonstrate that the CIHE can exist in magnetic crystals possessing C3v symmetry. Using a tight-binding model and realistic first-principles calculations on the metallic heterostructure, we find that the CIHE originates from the trigonal warping of the Fermi surface. Our observations highlight the critical role of crystal symmetry in generating new types of Hall effects.

14.
Sci Rep ; 14(1): 1210, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216630

RESUMO

This study aimed to evaluate the significance of chemotherapy (CT) among metaplastic breast cancer (MpBC), and to compare the survival outcomes between triple negative MpBC (MpBC-TNBC) and triple negative invasive ductal carcinoma (IDC-TNBC). SEER database was indexed to identify female unilateral primary MpBC diagnosed from 2010 to 2017. Patients were classified into neoadjuvant chemotherapy (NAC) with response (NAC-response), NAC-no response, adjuvant chemotherapy, and no CT. Breast cancer-specific survival (BCSS) and overall survival (OS) was estimated using the Kaplan-Meier method and compared by log-rank test. Cox regression was used to evaluate the independent prognostic factors. A 1:4 propensity score matching method was adopted to balance baseline differences. Altogether 1186 MpBC patients were enrolled, among them 181 received NAC, 647 received adjuvant CT and 358 did not receive any CT. Chemotherapy was an independent favorable prognostic factor. NAC-response and adjuvant CT had a significant or an obvious trend of survival improvement compared with NAC-no response or no CT. MpBC-TNBC was an independent unfavorable prognostic factor compared with IDC-TNBC. Among them, there was significant or trend of survival improvement among all TNBCs receiving NAC or adjuvant CT compared with no CT. Chemotherapy was of important significance to MpBC prognosis and should be integrated in comprehensive treatment for MpBC.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Prognóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Resultado do Tratamento , Estimativa de Kaplan-Meier , Estudos Retrospectivos , Quimioterapia Adjuvante/métodos
15.
Sci Rep ; 13(1): 21368, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049548

RESUMO

Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin's model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin's model was free with open access at http://jinmodel.com:3000/ . Jin's model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.


Assuntos
Colite Ulcerativa , Sistemas de Apoio a Decisões Clínicas , Adulto , Humanos , Colite Ulcerativa/diagnóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Colonoscopia
16.
J Am Chem Soc ; 145(49): 26756-26764, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38039269

RESUMO

The classical Au(I)/Au(III) redox couple chemistry has been limited to constructing C-C and C-X bonds, and thus, the exploration of the elementary reaction of gold redox coupling is very significant to enrich its organometallic features. Herein, we report the first visible-light-mediated, external oxidant-free Au(I)/Au(III) redox couple using commercially available Mn2(CO)10 to generate Mn-Au(III)-Mn intermediates for bimetallic redox coupling. A wide range of structurally diverse heterodinuclear and polynuclear L-Au(I)-Mn-L' complexes (19 examples, up to >99% yields) are readily constructed, providing a robust strategy for the concise construction of Au-Mn complexes under mild reaction conditions. The mechanistic studies together with DFT calculations support the radical oxidative addition of •Mn(CO)5 to gold and bimetallic reductive elimination mechanisms from highly active Mn-Au(III)-Mn species, representing an important step toward an elementary reaction in gold chemistry research. Furthermore, the resulting Au-Mn complexes exhibit unique catalytic activity, with which divergent reductive coupling of nitroarenes can readily afford azoxybenzenes, azobenzenes, and hydrazobenzenes in moderate to good yields.

17.
J Cancer ; 14(14): 2670-2685, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779877

RESUMO

Introduction: Fanconi anemia complementation group E (FANCE) is a subunit of fanconi anemia (FA) pathway and plays a key role in repairing DNA interstrand cross-links (ICLs) damage. We investigate detailed functions and mechanisms of FANCE in endometrial cancer (EC). Methods: FANCE protein and RNA expression in EC and non-cancerous tissues were detected by Western blotting (WB), immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) assays. Using lentiviral transfection and siRNA interference techniques, we constructed overexpressing FANCE (OE-FANCE) and FANCE-knockdown (FANCE-KD) EC cells. We then investigated DNA damage repair capacity of FANCE in EC cells including comet assay and γH2AX immunofluorescence assay. In vitro assays including CCK8, EDU and colony formation for chemoresistance and proliferation, transwell assay for metastasis were performed. Flow cytometer assay, cell cycle synchronization for cell cycle progression and EC cells RNA sequencing were determined. Finally, in vivo mouse models were used to detect tumor growth. Results: We found FANCE RNA and protein expression was significantly decreased in endometrioid adenocarcinoma (EAC) compared with normal and atypical hyperplasia endometrium. FANCE promoted the repair of ICL damage and double-strand break (DSB) in OE-FANCE EC cells. Furthermore, FANCE increased drug resistance in OE-FANCE EC cells by upregulating FA pathway and homologous recombination (HR) associated proteins. FANCE inhibited cell proliferation and metastasis through G2/M cell cycle arrest in vitro and vivo. FANCE participated in regulating several pathways. Conclusion: The study demonstrates the reduction of FANCE expression leads to genomic instability, thereby promoting the development of EC by regulating cell cycle.

18.
Environ Res ; 237(Pt 2): 116950, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37660876

RESUMO

Uranium pollution in groundwater environment has become an important issue of global concern. In this study, a strain of Desulfovibrio desulfuricans was isolated from the tailings of acid heap leaching, and was shown to be able to remove uranium from water via biosorption, bio-reduction, passive biomineralization under uranium stress, and active metabolically dependent bioaccumulation. This research explored the effects of nutrients, pH, initial uranium and sulfate concentration on the functional groups, uranium valence, and crystal size and morphology of uranium immobilization products. Results showed that tetravalent and hexavalent phosphorus-containing uranium minerals was both formed. In sulfate-containing water where Desulfovibrio desulfuricans A3-21ZLL can grow, the sequestration of uranium by bio-reduction was significantly enhanced compared to that with no sulfate loading or no growth. Ungrown Desulfovibrio desulfuricans A3-21ZLL or dead ones released inorganic phosphate group in response to the stress of uranium, which associated with soluble uranyl ion to form insoluble uranium-containing precipitates. This study revealed the influence of hydrochemical conditions on the mineralogy characteristics and spatial distribution of microbial uranium immobilization products. This study is conducive to the long-term and stable bioremediation of groundwater in decommissioned uranium mining area.

19.
BMC Musculoskelet Disord ; 24(1): 728, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700293

RESUMO

BACKGROUND: To investigate the risk factors for new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and to create a nomogram to predict the occurrence of new postoperative fractures. METHODS: This was a retrospective analysis of the clinical data of 529 OVCF patients who received PKP treatment in our hospital from June 2017 to June 2020. Based on whether there were new fractures within 2 years after surgery, the patients were divided into a new fracture group and a nonnew fracture group. Univariate and multivariate analyses were used to determine the risk factors for the occurrence of NVCFs after surgery. The data were randomly divided into a training set (75%) and a testing set (25%). Nomograms predicting the risk of NVCF occurrence were created based on the results of the multivariate analysis, and performance was evaluated using receiver operating characteristic curves (ROCs), calibration curves, and decision curve analyses (DCAs). A web calculator was created to give clinicians a more convenient interactive experience. RESULTS: A total of 56 patients (10.6%) had NVCFs after surgery. The univariate analysis showed significant differences in sex and the incidences of cerebrovascular disease, a positive fracture history, and bone cement intervertebral leakage between the two groups (P < 0.05). The multivariate analysis showed that sex [OR = 2.621, 95% CI (1.030-6.673), P = 0.043], cerebrovascular disease [OR = 28.522, 95% CI (8.749-92.989), P = 0.000], fracture history [OR = 12.298, 95% CI (6.250-24.199), P = 0.000], and bone cement intervertebral leakage [OR = 2.501, 95% CI (1.029-6.082), P = 0.043] were independent risk factors that were positively associated with the occurrence of NVCFs. The AUCs of the model were 0.795 (95% CI: 0.716-0.874) and 0.861 (95% CI: 0.749-0.974) in the training and testing sets, respectively, and the calibration curves showed high agreement between the predicted and actual states. The areas under the decision curve were 0.021 and 0.036, respectively. CONCLUSION: Female sex, cerebrovascular disease, fracture history and bone cement intervertebral leakage are risk factors for NVCF after PKP. Based on this, a highly accurate nomogram was developed, and a webpage calculator ( https://new-fracture.shinyapps.io/DynNomapp/ ) was created.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas da Coluna Vertebral , Idoso , Humanos , Feminino , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/epidemiologia , Fraturas por Compressão/etiologia , Nomogramas , Cimentos Ósseos/efeitos adversos , Cifoplastia/efeitos adversos , Estudos Retrospectivos
20.
Acc Chem Res ; 56(20): 2838-2850, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37751270

RESUMO

ConspectusCompared to traditionally used irreversible chemical reactions, dynamic covalent chemistry (DCC) including imine formation represents a more advanced technique in the preparation of molecules with complex structures and topologies, whose syntheses require the formation of many bonds. By allowing the occurrence of error checking and self-correcting, it is likely that the target molecules with high enough thermodynamic stability could be self-assembled in high or even quantitative yield. Two questions are raised herein. First, it becomes a central problem in self-assembly that how to endow a target product with high enough thermodynamic stability so that it can be produced as the major or the only product within the self-assembly library. Second, the reversible nature of dynamic bonds jeopardizes the intrinsic stability of the products. More specifically, the imine bond which represents the mostly used dynamic covalent bond, is apt to undergo hydrolysis in the presence of water. Developing new approaches to make imine more robust and compatible with water is thus of importance. In this account, we summarized the progress made in our group in the field of self-assembly based on C═N bond formation. In organic solvent where an imine bond is relatively robust, we focus on studying how to enhance the thermodynamic stability of a target molecule by introducing intramolecular forces. These noncovalent interactions either release enthalpy to favor the formation of the target molecule or preorganize the building blocks into specific conformations that mimic the product, so that the entropy loss of the formation of the latter is thus suppressed. In water, which often leads to imine hydrolysis, we developed two strategies to enhance the water-compatibility. By taking advantage of multivalency, namely, multiple bonds are often more robust than a single bond, self-assembly via condensation of imine was performed successfully in water, a solvent that is considered as forbidden zone of imine. Another approach is to replace typical imine with its more robust and water compatible derivatives, namely, either hydrazone or oxime, whose C═N bonds are generally less electrophilic compared to typical imine. With the water-compatible dynamic bonds in hand, a variety topological nontrivial molecules such as catenanes and knots was self-assembled successfully in aqueous media, driven by hydrophobic effect. When the self-assembled molecules in the form of rings and cages were designed for supramolecular purposes, water-compatibility endows a merit that allows the hosts to take advantage of hydrophobic effect to drive host-guest recognition, enabling various tasks to be accomplished, such as separation of guest isomers with similar physical properties, recognition of highly hydrated anions, as well as stabilization of guest dimers.

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