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1.
Front Immunol ; 15: 1360219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745667

RESUMO

Background: Regulatory B cells (Bregs) play a pivotal role in suppressing immune responses, yet there is still a lack of cell surface markers that can rigorously identify them. In mouse models for multiple sclerosis (MS), TIM-1 or TIGIT expression on B cells is required for maintaining self-tolerance and regulating autoimmunity to the central nervous system. Here we investigated the activities of human memory B cells that differentially express TIM-1 and TIGIT to determine their potential regulatory function in healthy donors and patients with relapsing-remitting (RR) MS. Methods: FACS-sorted TIM-1+/-TIGIT+/- memory B (memB) cells co-cultured with allogenic CD4+ T cells were analyzed for proliferation and induction of inflammatory markers using flow cytometry and cytokine quantification, to determine Th1/Th17 cell differentiation. Transcriptional differences were assessed by SMARTSeq2 RNA sequencing analysis. Results: TIM-1-TIGIT- double negative (DN) memB cells strongly induce T cell proliferation and pro-inflammatory cytokine expression. The TIM-1+ memB cells enabled low levels of CD4+ T cell activation and gave rise to T cells that co-express IL-10 with IFNγ and IL-17A or FoxP3. T cells cultured with the TIM-1+TIGIT+ double positive (DP) memB cells exhibited reduced proliferation and IFNγ, IL-17A, TNFα, and GM-CSF expression, and exhibited strong regulation in Breg suppression assays. The functional activity suggests the DP memB cells are a bonafide Breg population. However, MS DP memB cells were less inhibitory than HC DP memB cells. A retrospective longitudinal study of anti-CD20 treated patients found that post-treatment DP memB cell frequency and absolute number were associated with response to therapy. Transcriptomic analyses indicated that the dysfunctional MS-derived DP memB/Breg population exhibited increased expression of genes associated with T cell activation and survival (CD80, ZNF10, PIK3CA), and had distinct gene expression compared to the TIGIT+ or TIM-1+ memB cells. Conclusion: These findings demonstrate that TIM-1/TIGIT expressing memory B cell subsets have distinct functionalities. Co-expression of TIM-1 and TIGIT defines a regulatory memory B cell subset that is functionally impaired in MS.


Assuntos
Linfócitos B Reguladores , Receptor Celular 1 do Vírus da Hepatite A , Receptores Imunológicos , Humanos , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/genética , Feminino , Masculino , Adulto , Células B de Memória/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/metabolismo , Citocinas/metabolismo , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Ativação Linfocitária/imunologia , Pessoa de Meia-Idade , Células Cultivadas , Diferenciação Celular/imunologia , Memória Imunológica
2.
Chem Commun (Camb) ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700119

RESUMO

A highly efficient and stable green phosphor with a narrow emission-band in a hexagonal aluminate was synthesized based on the energy transfer between Eu2+ and Mn2+ luminescence centers. The related mechanism was elucidated from the viewpoints of the crystal structure and energy level, providing insights for designing novel phosphors with high performance.

3.
Food Funct ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739010

RESUMO

Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.

4.
Langmuir ; 40(18): 9579-9591, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38657205

RESUMO

Herein, a fiber-supported iron-based ionic liquid as a type of fibrous catalyst has been developed for the synthesis of bioactive 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) via three-component Biginelli reactions in a cleaner manner. The described fibrous catalyst was obtained from the commercially available polyetheretherketone (PEEK) fiber by postfunctionalization processes and was characterized and analyzed in detail by means of diversified technologies. Furthermore, the fiber-supported iron-based ionic liquids could mediate the classical three-component Biginelli reactions to proceed smoothly to gain a variety of substituted DHPMs with yields of up to 99%. The superior catalytic activities of the fibrous catalyst were ascribed to the quasi-homogeneous medium by ionic liquids generated in the surface layer of the PEEK fiber, which could afford an appropriate reaction zone and could further be available for the aggregation of substrates to facilitate the three-component reaction. Notably, the fibrous catalyst is available for recycling over 10 runs just by a pair of tweezers, and the operational procedure was capable of enlarging the catalytic system to the gram-scale without any performance degradation, which provided a cleaner manner to take advantage of the iron-based catalyst in organic synthesis with potential industrialization prospects.

5.
Urolithiasis ; 52(1): 72, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683224

RESUMO

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process.


Assuntos
Hidronefrose , Pelve Renal , Litotripsia , Cálculos Ureterais , Humanos , Litotripsia/efeitos adversos , Masculino , Estudos Prospectivos , Feminino , Hidronefrose/etiologia , Pessoa de Meia-Idade , Adulto , Cálculos Ureterais/complicações , Cálculos Ureterais/terapia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Tomografia Computadorizada por Raios X , Urina/microbiologia , Medição de Risco , Sepse/etiologia , Sepse/complicações , Fatores de Risco , Valor Preditivo dos Testes , Índice de Gravidade de Doença
6.
Environ Health ; 23(1): 38, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609943

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.


Assuntos
Artrite Reumatoide , Fluorocarbonos , Adulto , Feminino , Masculino , Humanos , Inquéritos Nutricionais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/epidemiologia , Razão de Chances , Autorrelato
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 403-410, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38645849

RESUMO

Objective: To explore the efficacy and safety of medical thoracoscopic bulla volume reduction for the treatment of chronic obstructive pulmonary disease (COPD) combined with giant emphysematous bullae (GEB). Methods: A total of 66 patients with COPD combined with GEB were enrolled in the study. All the subjects received treatment at Zhengzhou Central Hospital affiliated with Zhengzhou University between March 2021 and December 2022. The subjects were divided into two groups, a medical thoracoscope group consisting of 30 cases treated with medical thoracoscopic bulla volume reduction and a surgical thoracoscope group consisting of 36 cases treated by video-assisted thoracoscopic surgery. All patients were followed up before discharge and 3 months and 6 months after discharge. The preoperative and postoperative levels of the pulmonary function, 6-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores and differences in postoperative complications were compared between the two groups. The operative duration, postoperative length-of-stay, and surgical costs and hospitalization bills, and the maximum visual analog scale (VAS) pain scores at 24 h after the procedure were assessed. Results: The baseline data of the two groups were comparable, showing no statistically significant difference. The forced expiratory volume in 1 second (FEV1) 6 months after the procedures improved in both the medical thoracoscopy group ([0.78±0.29] L vs. [1.02±0.31] L, P<0.001) and the surgical thoracoscopy group ([0.80±0.21] L vs. [1.03±0.23] L, P<0.001) compared to that before the procedures. Improvements to a certain degree in 6MWT and SGRQ scores were also observed in the two groups at 3 months and 6 months after the procedures (P<0.05). In addition, no statistically significant difference in these indexes was observed during the follow-up period of the patients in the two groups. There was no significant difference in operating time between the two groups. The medical thoracoscopy group had shorter postoperative length-of-stay ([7.3±2.6] d) and 24-hour postoperative VAS pain scores (3.0 [2.0, 3.3]) than the surgical thoracoscopic group did ([10.4±4.3] d and 4.5 [3.0, 5.0], respectively), with the differences being statistically significant (P<0.05). Surgical cost and total hospitalization bills were lower in the medical thoracoscopy group than those in the surgical thoracoscopy group (P<0.05). The complication rate in the medical thoracoscopy group was lower than that in the surgical thoracoscopy group (46.7% vs. 52.8%), but the difference was not statistically significant. Conclusion: Medical thoracoscopic reduction of bulla volume can significantly improve the pulmonary function, quality of life, and exercise tolerance of patients with COPD combined with GEB, and it can reduce postoperative short-term pain and shorten postoperative length-of-stay. The procedure has the advantages of minimal invasiveness, quick recovery, and low costs. Hence extensive clinical application is warranted.


Assuntos
Vesícula , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Cirurgia Torácica Vídeoassistida , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/cirurgia , Vesícula/cirurgia , Masculino , Feminino , Tempo de Internação , Toracoscopia/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Pessoa de Meia-Idade , Idoso
8.
J Phys Chem Lett ; 15(16): 4375-4383, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38620049

RESUMO

Metal-free perovskites (MFPs) have recently become a newcomer in X-ray detection due to their flexibility and low toxicity characteristics. However, their photoelectronic properties and stability should be further improved mainly through materials design. Here, the aminoazanium of DABCO2+ was developed for the preparation of NDABCO-NH4Br3 (NDABCO = N-amino-N'-diazabicyclo[2.2.2]octonium) single crystals (SCs), and its physical properties, intermolecular interactions, and device performance were systematically explored. Notably, NDABCO-NH4Br3 can achieve improved stability by enlarging defect formation energy and inducing abundant intermolecular forces. Moreover, the slight lattice distortion could ensure the weakening electron-phonon coupling for improving carrier transport. In particular, the slight lattice distortion after the long-chain NDABCO2+ introduction could retard thermal expansion for the preparation of high-quality crystals. Finally, the corresponding X-ray detector delivered a moderate sensitivity of 623.3 µC Gyair-1 cm-2. This work provides a novel strategy through rationally designed organic cations to balance the material stability and device performance.

9.
Bioconjug Chem ; 35(4): 540-550, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38557019

RESUMO

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.


Assuntos
Ouro , Nanopartículas Metálicas , Ouro/toxicidade , Ouro/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química
10.
ChemMedChem ; : e202400189, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632104

RESUMO

In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salts "4-(2-hydroxyethyl)benzenediazonium salt" is presented. Cyclic voltammetry procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i.e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical properties, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characterization techniques, such as cyclic voltammetry (CV), atomic force microscopy (AFM), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS), etc., thereby confirming the successful grafting of hydroxyl groups onto the TiN surface. The experiments on DNA synthesis aimed to explore the potential of modified TiN electrode as a novel platform for DNA data storage applications and the corresponding proof-of-principle was accomplished by the process of coupling Cy3-phosphoramidite. Finally, the experiments were successfully reproduced on the randomly selected sites of the modified TiN microarray chips demonstrating the potential of technical protocol to extend applications in future bioelectronic devices, such as bio-sensing, high-throughput DNA synthesis, and molecular manipulation.

11.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629931

RESUMO

The long-term monitoring stability of electronic current transformers is crucial for accurately obtaining the current signal of the power grid. However, it is difficult to accurately distinguish between the fluctuation of non-stationary random signals on the primary side of the power grid and the gradual error of the transformers themselves. A current transformer error prediction model, CNN-MHA-BiLSTM, based on the golden jackal optimization (GJO) algorithm, which is used to obtain the optimal parameter values, bidirectional long short-term memory (BiLSTM) network, convolutional neural networks (CNNs), and multi-head attention (MHA), is proposed to address the difficulty of measuring error evaluation. This model can be used to determine the operation of transformers and can be widely applied to assist in determining the stability of transformer operation and early faults. First, CNN is used to mine the vertical detail features of error data at a certain moment, improving the speed of error prediction. Furthermore, a cascaded network with BiLSTM as the core is constructed to extract the horizontal historical features of the error data. The GJO algorithm is used to adjust the parameters of the BiLSTM model; optimize the hidden layer nodes, training frequency, and learning rate; and integrate MHA mechanism to promote the model to pay attention to the characteristic changes of the data in order to improve the accuracy of error prediction. Finally, this method is applied to the operation data of transformer in substations, and four time periods of data are selected to verify the model effectiveness of the current transformer dataset. The analysis results of single step and multi-step examples indicate that the proposed model has significant advantages in terms of accuracy and stability in error prediction.

12.
Front Bioeng Biotechnol ; 12: 1352098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585708

RESUMO

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

14.
Asian J Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604851

RESUMO

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

15.
Tissue Eng Regen Med ; 21(4): 595-608, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38466361

RESUMO

BACKGROUND: The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis. METHODS: NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments. RESULTS: Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 in vitro and in vivo. CONCLUSION: Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.


Assuntos
Fator 4 Ativador da Transcrição , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Fator de Transcrição STAT4 , Regulação para Cima , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Animais , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT4/genética , Invasividade Neoplásica , Linhagem Celular Tumoral , Células A549 , Camundongos Nus , Camundongos , Apoptose , Feminino , Masculino , Movimento Celular , Camundongos Endogâmicos BALB C
16.
Blood ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446568

RESUMO

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

17.
Sci Rep ; 14(1): 7099, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531885

RESUMO

Rare earth doped up-conversion luminescent nano-materials exhibit abundant emission colors under suitable excitation condition. In this work, NaYF4:Er/Ho@NaYF4 and NaYbF4:Tm@NaYF4 nanoparticles were synthesized by co-precipitation method. The pure red emission can be realized by the designed NaYF4:Er/Ho@NaYF4 nanocrystals and the R/Gs reach 23.3 and 25 under excitations of 980 and 1550 nm lasers, respectively. The R/G declines as the power increasing with the emission color changing from red to yellow, which is due to the quick saturation of the energy levels, radiating red emissions. Meanwhile, the emission intensity of NaYbF4:Tm@NaYF4 nanocrystals increases by 58.3 folds after encasing the inert shell NaYF4 and the CIE color coordinate reaches (0.1646, 0.0602) under 980 nm laser excitation. Furthermore, broad range multicolor from blue to red and yellow up-conversion emissions is achieved by mixing NaYF4:Er/Ho@NaYF4 and NaYbF4:Tm@NaYF4 nanocrystals, which could be applied to colorful displaying, security anti-counterfeiting and information coding.

18.
J Evid Based Med ; 17(1): 187-206, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38502879

RESUMO

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Humanos , Medicina Tradicional Chinesa/métodos , Deslocamento do Disco Intervertebral/tratamento farmacológico
19.
Sci Total Environ ; 926: 171791, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508249

RESUMO

Fine particulate matter (PM2.5) from vehicle exhaust is typically emitted at breathing height and thus imposes severe adverse effects on human health and air quality. However, there is currently limited knowledge on the characteristics of PM2.5 in exhaust, specifically its chemical components, at different ambient temperatures. Particulate emissions from typical light-duty gasoline vehicles (LDGVs) were investigated on a chassis dynamometer according to the Worldwide Harmonized Light-Duty Test Cycle at ambient temperatures of 38 °C, 28 °C, 15 °C, 5 °C and - 7 °C. The results showed a significant increase in particulate mass (PM) and particle number (PN) emissions with decreasing ambient temperature, particularly during cold starts below 5 °C. The particle size distributions exhibited distinct bimodal patterns, with accumulation-mode (AM) particles (60-125 nm) dominating the gasoline direct injection (GDI) distribution and nucleation-mode (NM) particles (8-12 nm) dominating the port fuel injection (PFI) distribution. AM particles were more temperature-sensitive than NM particles. Lower temperatures produced higher emissions of elements, carbonaceous components, and large-ring polycyclic aromatic hydrocarbons, while water-soluble ions showed an opposite trend. The total toxic equivalent, primarily influenced by benzo[a]pyrene, was significantly higher at -7 °C. The penalty distribution of LDGV PM and PN, defined by comparing the emissions at the various temperatures to those at regulated temperatures (23-30 °C), exhibited notable temporal heterogeneity (winter > autumn > spring > summer) and spatial heterogeneity (northern China > southern China). These findings are essential for establishing more stringent vehicle emission standards and improving emission models in cold environments.

20.
Bioact Mater ; 36: 48-61, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38434148

RESUMO

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

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