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1.
Proc Natl Acad Sci U S A ; 120(41): e2221653120, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37788309

RESUMO

Fatty acid oxidation (FAO) fuels many cancers. However, knowledge of pathways that drive FAO in cancer remains unclear. Here, we revealed that valosin-containing protein (VCP) upregulates FAO to promote colorectal cancer growth. Mechanistically, nuclear VCP binds to histone deacetylase 1 (HDAC1) and facilitates its degradation, thus promoting the transcription of FAO genes, including the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). FAO is an alternative fuel for cancer cells in environments exhibiting limited glucose availability. We observed that a VCP inhibitor blocked the upregulation of FAO activity and CPT1A expression triggered by metformin in colorectal cancer (CRC) cells. Combined VCP inhibitor and metformin prove more effective than either agent alone in culture and in vivo. Our study illustrates the molecular mechanism underlying the regulation of FAO by nuclear VCP and demonstrates the potential therapeutic utility of VCP inhibitor and metformin combination treatment for colorectal cancer.


Assuntos
Neoplasias Colorretais , Metformina , Humanos , Proteína com Valosina/genética , Proteína com Valosina/metabolismo , Processos Neoplásicos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ácidos Graxos/metabolismo , Metformina/farmacologia , Carnitina O-Palmitoiltransferase/metabolismo , Oxirredução
2.
Plant Physiol ; 194(4): 2709-2723, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38206193

RESUMO

Plants and their associated microbes live in complicated, changeable, and unpredictable environments. They usually interact with each other in many ways through multidimensional, multiscale, and multilevel coupling manners, leading to challenges in the coexistence of randomness and determinism or continuity and discreteness. Gaining a deeper understanding of these diverse interaction mechanisms can facilitate the development of data-mining theories and methods for complex systems, coupled modeling for systems with different spatiotemporal scales and functional properties, or even a universal theory of information and information interactions. In this study, we use a "closed-loop" model to present a plant-microbe interaction system and describe the probable functions of microbial natural products. Specifically, we report a rhizosphere species, Streptomyces ginsengnesis G7, which produces polyketide lydicamycins and other active metabolites. Interestingly, these distinct molecules have the potential to function both as antibiotics and as herbicides for crop protection. Detailed laboratory experiments conducted in Arabidopsis (Arabidopsis thaliana), combined with a comprehensive bioinformatics analysis, allow us to rationalize a model for this specific plant-microbe interaction process. Our work reveals the benefits of exploring otherwise neglected resources for the identification of potential functional molecules and provides a reference to better understand the system biology of complex ecosystems.


Assuntos
Arabidopsis , Microbiota , Panax , Streptomyces , Rizosfera , Plantas/metabolismo , Microbiologia do Solo
3.
EMBO Rep ; 24(2): e55503, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36440617

RESUMO

Myeloid cell development in bone marrow is essential for the maintenance of peripheral immune homeostasis. However, the role of intracellular protein trafficking pathways during myeloid cell differentiation is currently unknown. By mining bioinformatics data, we identify trafficking protein particle complex subunit 1 (TRAPPC1) as continuously upregulated during myeloid cell development. Using inducible ER-TRAPPC1 knockout mice and bone marrow chimeric mouse models, we demonstrate that TRAPPC1 deficiency causes severe monocyte and neutrophil defects, accompanied by a selective decrease in common myeloid progenitors (CMPs) and subsequent cell subsets in bone marrow. TRAPPC1-deleted CMPs differentiate poorly into monocytes and neutrophils in vivo and in vitro, in addition to exhibiting enhanced endoplasmic reticulum stress and apoptosis via a Ca2+ -mitochondria-dependent pathway. Cell cycle arrest and senescence of TRAPPC1-deleted CMPs are mediated by the activation of pancreatic endoplasmic reticulum kinase and the upregulation of cyclin-dependent kinase inhibitor p21. This study reveals the essential role of TRAPPC1 in the maintenance and differentiation of CMPs and highlights the significance of protein processing and trafficking processes in myeloid cell development.


Assuntos
Medula Óssea , Células Progenitoras Mieloides , Proteínas de Transporte Vesicular , Animais , Camundongos , Medula Óssea/metabolismo , Diferenciação Celular , Camundongos Knockout , Monócitos , Células Progenitoras Mieloides/metabolismo , Neutrófilos , Proteínas de Transporte Vesicular/metabolismo
4.
Small ; : e2401308, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773889

RESUMO

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

5.
New Phytol ; 241(4): 1866-1876, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38124293

RESUMO

Image-based high-throughput phenotyping promises the rapid determination of functional traits in large plant populations. However, interpretation of some traits - such as those related to photosynthesis or transpiration rates - is only meaningful if the irradiance absorbed by the measured leaves is known, which can differ greatly between different parts of the same plant and within canopies. No feasible method currently exists to rapidly measure absorbed irradiance in three-dimensional plants and canopies. We developed a method and protocols to derive absorbed irradiance at any visible part of a canopy with a thermal camera, by fitting a leaf energy balance model to transient changes in leaf temperature. Leaves were exposed to short light pulses (30 s) that were not long enough to trigger stomatal opening but strong enough to induce transient changes in leaf temperature that was proportional to the absorbed irradiance. The method was successfully validated against point measurements of absorbed irradiance in plant species with relatively simple architecture (sweet pepper, cucumber, tomato, and lettuce). Once calibrated, the model was used to produce absorbed irradiance maps from thermograms. Our method opens new avenues for the interpretation of plant responses derived from imaging techniques and can be adapted to existing high-throughput phenotyping platforms.


Assuntos
Cucumis sativus , Folhas de Planta , Folhas de Planta/fisiologia , Fotossíntese/fisiologia , Plantas , Fenótipo
6.
Soft Matter ; 20(17): 3666-3675, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623704

RESUMO

Hydrogel-based flexible electronic devices serve as a next-generation bridge for human-machine interaction and find extensive applications in clinical therapy, military equipment, and wearable devices. However, the mechanical mismatch between hydrogels and human tissues, coupled with the failure of conformal interfaces, hinders the transmission of information between living organisms and flexible devices, which resulted in the instability and low fidelity of signals, especially in the acquisition of electromyographic (EMG) and electrocardiographic (ECG) signals. In this study, we designed an ion-conductive hydrogel (ICHgel) utilizing multiple physical interactions, successfully applied for human motion monitoring and the collection of epidermal physiological signals. By incorporating fumed silica (F-SiO2) nanoparticles and calcium chloride into an interpenetrating network (IPN) composed of polyvinyl alcohol (PVA) and polyacrylamide (AAm)/acrylic acid (AA) chains, the ICHgel exhibited exceptional tunable stretchability (>1450% strain) and conductivity (10.58 ± 0.85 S m-1). Additionally, the outstanding adhesion of the ICHgel proved to be a critical factor for effective communication between epidermal tissues and flexible devices. Demonstrating its capability to acquire stable electromechanical signals, the ICHgel was attached to different parts of the human body. More importantly, as a flexible electrode, the ICHgel outperformed commercial Ag/AgCl electrodes in the collection of ECG and EMG signals. In summary, the synthesized ICHgel with its outstanding conformal interface capabilities and mechanical adaptability paves the way for enhanced human-machine interaction, fostering the development of flexible electronic devices.


Assuntos
Acrilatos , Condutividade Elétrica , Hidrogéis , Humanos , Hidrogéis/química , Dispositivos Eletrônicos Vestíveis , Resinas Acrílicas/química , Álcool de Polivinil/química , Eletromiografia , Eletrocardiografia , Adesivos/química , Dióxido de Silício/química , Eletrodos
7.
Environ Sci Technol ; 58(6): 2902-2911, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38294202

RESUMO

Conventional biological nutrient removal processes rely on external aeration and produce significant carbon dioxide (CO2) emissions. This study constructed a phototrophic simultaneous nitrification-denitrification phosphorus removal (P-SNDPR) system to treat low carbon to nitrogen (C/N) ratios wastewater and investigated the impact of sludge retention time (SRT) on nutrient removal performance, nitrogen conversion pathway, and microbial structure. Results showed that the P-SNDPR system at SRT of 15 days had the highest nutrient removal capacity, achieving over 85% and 98% removal of nitrogen and phosphorus, respectively, meanwhile maintaining minimal CO2 emissions. Nitrogen removal was mainly through assimilation at SRTs of 5 and 10 days, and nitrification-denitrification at SRTs of 15 and 20 days. Stable partial nitrification was facilitated by photoinhibition and low DO levels. Flow cytometry sorting technique results revealed SRT drove community structural changes in translational activity (BONCAT+) microbes, where BONCAT+ microbes were mainly simultaneous nitrogen and phosphorus removal bacteria (Candidatus Accumulibacter), denitrifying bacteria (Candidatus Competibacter and Plasticicumulans), ammonia-oxidizing bacteria (Nitrosomonas), and microalgae (Chlorella and Dictyosphaerium). The P-SNDPR system represents a novel, carbon-neutral process for efficient nutrient removal from low C/N ratio wastewater without aeration and external carbon source additions.


Assuntos
Chlorella , Águas Residuárias , Nitrificação , Desnitrificação , Fósforo/metabolismo , Nitrogênio/química , Nitrogênio/metabolismo , Dióxido de Carbono , Chlorella/metabolismo , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos/microbiologia , Esgotos/microbiologia
8.
Mol Biol Rep ; 51(1): 650, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734811

RESUMO

BACKGROUND: Vitiligo is a common autoimmune skin disease. Capsaicin has been found to exert a positive effect on vitiligo treatment, and mesenchymal stem cells (MSCs) are also confirmed to be an ideal cell type. This study aimed to explore the influence of capsaicin combined with stem cells on the treatment of vitiligo and to confirm the molecular mechanism of capsaicin combined with stem cells in treating vitiligo. METHODS AND RESULTS: PIG3V cell proliferation and apoptosis were detected using CCK-8 and TUNEL assays, MitoSOX Red fluorescence staining was used to measure the mitochondrial ROS level, and JC-1 staining was used to detect the mitochondrial membrane potential. The expression of related genes and proteins was detected using RT‒qPCR and Western blotting. Coimmunoprecipitation was used to analyze the protein interactions between HSP70 and TLR4 or between TLR4 and mTOR. The results showed higher expression of HSP70 in PIG3V cells than in PIG1 cells. The overexpression of HSP70 reduced the proliferation of PIG3V cells, promoted apoptosis, and aggravated mitochondrial dysfunction and autophagy abnormalities. The expression of HSP70 could be inhibited by capsaicin combined with MSCs, which increased the levels of Tyr, Tyrp1 and DCT, promoted the proliferation of PIG3V cells, inhibited apoptosis, activated autophagy, and improved mitochondrial dysfunction. In addition, capsaicin combined with MSCs regulated the expression of TLR4 through HSP70 and subsequently affected the mTOR/FAK signaling pathway CONCLUSIONS: Capsaicin combined with MSCs inhibits TLR4 through HSP70, and the mTOR/FAK signaling pathway is inhibited to alleviate mitochondrial dysfunction and autophagy abnormalities in PIG3V cells.


Assuntos
Apoptose , Capsaicina , Proliferação de Células , Proteínas de Choque Térmico HSP70 , Melanócitos , Mitocôndrias , Transdução de Sinais , Serina-Treonina Quinases TOR , Receptor 4 Toll-Like , Vitiligo , Receptor 4 Toll-Like/metabolismo , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Serina-Treonina Quinases TOR/metabolismo , Vitiligo/metabolismo , Vitiligo/tratamento farmacológico , Capsaicina/farmacologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Melanócitos/metabolismo , Melanócitos/efeitos dos fármacos , Linhagem Celular , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Autofagia/efeitos dos fármacos
9.
BMC Endocr Disord ; 24(1): 77, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831300

RESUMO

OBJECTIVE: This study aimed to analyze the factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: Baseline data, encompassing basic information, lifestyle habits, and treatment of 305 T2DM patients from March 2021 to January 2023, were collected and analyzed using SPSS 26.0 software. RESULTS: Univariate and multivariate logistic regression analyses identified insulin therapy (OR = 2.233; 95%Cl = 1.013-4.520; P = 0.026) and regular clinic visits (OR = 0.567; 95%Cl = 0.330-0.973; P = 0.040) as independent factors influencing glycemic control. No observed interactions between the two variables were noted. CONCLUSION: History of insulin therapy and regular clinic visits were significantly and independently associated with glycated hemoglobin control in T2DM patients. Tailored interventions based on individual circumstances are recommended to optimize glycemic control.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Controle Glicêmico , Hipoglicemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Estudos Transversais , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , Glicemia/análise , Glicemia/metabolismo , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Idoso , Insulina/uso terapêutico , Insulina/administração & dosagem , Adulto , Prognóstico
10.
Photodermatol Photoimmunol Photomed ; 40(3): e12970, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685665

RESUMO

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.


Assuntos
Benzodioxóis , Movimento Celular , Proliferação de Células , Melaninas , Piperidinas , Humanos , Alcaloides/farmacologia , Benzodioxóis/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Melaninas/biossíntese , Melanócitos/metabolismo , Melanócitos/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lasers , Vitiligo/tratamento farmacológico , Vitiligo/terapia
11.
Oral Dis ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462960

RESUMO

OBJECTIVES: To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis. METHODS: Conditioned media derived from preosteoclasts pretreated with the CTSK inhibitor odanacatib (ODN), ODN supplemented small interfering RNA targeting PDGF-BB (si-PDGF-BB), or PBS were prepared, to assess their proangiogenic effects on endothelial cells (HUVECs). A series of angiogenic-related assays were conducted to evaluate HUVEC proliferation, migration, and tube formation abilities in vitro. In addition, qRT-PCR and Western blot assays were employed to examine the expression levels of genes/proteins related to PDGF-BB/PDGFR-ß axis components. A mouse periodontitis model was established to evaluate the effects of CTSK inhibition on type H vessel formation. RESULTS: CTSK inhibition promoted PDGF-BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs in vitro. However, the conditioned medium from preosteoclasts pretreated by si-PDGF-BB impaired the angiogenic activities of HUVECs. This promoted angiogenesis function by CTSK inhibition may be mediated by the PDGF-BB/PDGFR-ß axis. Functionally, in vivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis. CONCLUSION: CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF-BB/PDGFR-ß axis.

12.
Nephrology (Carlton) ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637907

RESUMO

AIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children. METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed. RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis. CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".

13.
Skin Res Technol ; 30(2): e13612, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348763

RESUMO

OBJECTIVE: In this study, the safety and efficacy of scalp repair serum microneedles combined with oral drug administration and topical medication were investigated for the treatment of moderate to severe androgenetic alopecia. METHODS: Twenty patients, consisting of 4 males and 16 females, who sought treatment for moderate to severe androgenetic alopecia at our hair medicine research center alopecia specialty clinic between August and December 2022 were randomly selected for the study. Male patients underwent oral administration of finasteride topical application of 5% minoxidil, and biweekly scalp repair serum microneedle therapy. Female patients were administered spironolactone or Diane-35 orally and applied 2% minoxidil topically, paired with biweekly scalp repair serum microneedle therapy sessions. After seven treatments, the scalp repair serum microneedle was discontinued, but oral administration and topical applications were continued, followed by a 1-month follow-up. Using a hair dermoscopy, hair follicles in a fixed region on the top of the head were manually counted per unit area to evaluate the hair restoration status of the patients quantitatively. RESULTS: All 20 patients completed 3 months of combined therapy and a 1-month follow-up. On average, the patients experienced an increase of 42.6 hairs, with an efficiency rate of 100%. Significant differences were observed in hair count between any two of the first seven treatments (p < 0.001). A significant negative correlation was discovered between the initial pre-treatment hair count and the total improvement of hair (p < 0.001), indicating that the greater the degree of hair loss before treatment, the more pronounced the improvement. CONCLUSION: Scalp repair serum microneedle combined therapy in moderate to severe androgenetic alopecia significantly reduces the number of microneedle treatments required, enhances treatment efficacy, and improves therapeutic outcomes.


Assuntos
Minoxidil , Couro Cabeludo , Humanos , Masculino , Feminino , Minoxidil/uso terapêutico , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Cabelo , Resultado do Tratamento
14.
Skin Res Technol ; 30(1): e13550, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38174801

RESUMO

OBJECTIVE: To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. METHODS: Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. RESULT: A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12 ± 14.70 (17 âˆ¼ 85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self-evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF- α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non-affordable price. CONCLUSIONS: In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto Jovem , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Estudos Retrospectivos , Ustekinumab/uso terapêutico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Acta Biochim Biophys Sin (Shanghai) ; 56(6): 866-878, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38606479

RESUMO

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Células-Tronco Neoplásicas , RNA Longo não Codificante , Animais , Feminino , Humanos , Masculino , Camundongos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética
16.
Proc Natl Acad Sci U S A ; 118(21)2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34001600

RESUMO

G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4-forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS-SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS-SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor-binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.


Assuntos
Proteínas de Ligação a DNA/ultraestrutura , Quadruplex G , Genoma Humano/genética , Conformação de Ácido Nucleico , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Sequências Reguladoras de Ácido Nucleico/genética , Sítio de Iniciação de Transcrição , Ativação Transcricional/genética
17.
Sensors (Basel) ; 24(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257705

RESUMO

Thin-walled aluminum alloy parts are widely used in the aerospace field because of their favorable characteristics that cater to various applications. However, they are easily deformed during milling, leading to a low pass rate of workpieces. On the basis of on-machine measurement (OMM) and surrogate stiffness models (SSMs), we developed an iterative optimization compensation method in this study to overcome the machining deformation of thin-walled parts. In the error compensation process, the time-varying factors of workpiece stiffness and the impact of prediction model errors were considered. First, we performed machining deformation simulation and information extraction on the key nodes of the machined surface, and an SSM containing the stiffness information of discrete nodes of each cutting layer was established. Subsequently, the machining errors were monitored through intermittent OMM to suppress the adverse impact of prediction model errors. Further, an interlayer correction coefficient was introduced in the compensation process to iteratively correct the prediction model error of each node in the SSM along the depth direction, and a correction coefficient between parts was introduced to realize the iterative correction of the prediction model for the same node position between different parts. Finally, the feasibility of the proposed method was verified through multiple sets of actual machining experiments on thin-walled parts with added pads.

18.
Asia Pac J Clin Nutr ; 33(1): 102-110, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494692

RESUMO

BACKGROUND AND OBJECTIVES: The effect of different coffee and tea consumption on postprandial glucose and lipid metabolism has never been reported previously. The aim of the present study was to investigate the effect of different coffee or tea consumption at breakfast on postprandial cardiometabolic risk factors in healthy individuals. METHODS AND STUDY DESIGN: Eighteen healthy young subjects completed the trial. After 8-hour overnight fast, volunteers either ingested water, freeze-dried coffee, spray-dried coffee, green tea, black tea or oolong tea together with a breakfast consisting of an egg and 180g deep-fried dough sticks. Blood was drawn at 0h, 0.5h, 1h, 2h, and 3h. RESULTS: The differences in triglyceride (TG) values relative to the baseline levels at 2h and 3h of green tea was significantly decreased compared with black tea and oolong tea (p<0.05). Compared with black tea, green tea and oolong tea significantly reduced postprandial total cholesterol (TC) levels (p<0.05, p<0.01), respectively. Furthermore, the serum concentrations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were substantially decreased after oolong tea consumption compared with black tea (p<0.05, p<0.01). CONCLUSIONS: Green tea ingestion can lower the elevation of serum TG and TC levels after high-fat or high-cholesterol diets. Our findings have far-reaching implications given the widespread use of coffee and tea and the current concern over cardiometabolic risk factors.


Assuntos
Fatores de Risco Cardiometabólico , Café , Humanos , Estudos Cross-Over , Chá , LDL-Colesterol
19.
Nano Lett ; 23(21): 9887-9893, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37870769

RESUMO

For the practical applications in solar cells and photodetectors, semiconductor colloidal nanocrystals (NCs) are assembled into a high-concentration film with carrier transport characteristics, the full understanding and effective control of which are critical for the achievement of high light-to-electricity conversion efficiencies. Here we have applied transient absorption microscopy to the solid film of giant CdSe/CdS NCs and discovered that at high pump fluences the carrier transport could reach a long distance of ∼2 µm within ∼30 ps after laser pulse excitation. This intriguing behavior is attributed to the metal-insulator transition and the associated bandlike transport, which are promoted by the enhanced electronic coupling among neighboring NCs with extended wave functions overlap of the excited-state charge carriers. Besides providing fundamental transport information in the regime of high laser pump fluences, the above findings shed light on the rational design of high-power light detecting schemes based on colloidal NCs.

20.
J Environ Manage ; 351: 119839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104464

RESUMO

Photo-enhanced Biological Phosphorus Removal (PEBPR) systems, promising wastewater treatment technology, offer efficient phosphorus removal without external oxygen. However, comprehending the impact of sludge retention time (SRT) on the system is crucial for successful implementation. This study investigated the SRT effect on nutrient fate, microbial community, and bacterial phototolerance in PEBPR systems. PEBPR systems exhibited good bacterial phototolerance at SRT of 10, 15, and 20 d, with optimal phosphorus-accumulation metabolism observed at SRT of 10 and 15d. However, at SRT of 5d, increased light sensitivity and glycogen-accumulating organisms (GAOs) growth resulted in poor P removal (71.9%). Accumulibacter-IIC were the dominant P accumulating organisms (PAOs) at SRT of 10, 15, and 20 d. Accumulibacter-I, IIC and IIF were the major PAOs at SRT of 5 d. The decrease in SRT promoted the microalgal population diversity, and Dictyosphaerium and Chlorella were the major microalgal species in this study. Flow cytometry results revealed high light intensity triggered intracellular Fe2+ efflux, limiting translation activity and metabolism. Moreover, PAOs had lower phototolerance than GAOs due to Poly-P bound intracellular Mg2+ affecting enzyme activity. This study provides an in-depth understanding of PEBPR systems operation strategy toward environmentally sustainable wastewater treatment.


Assuntos
Chlorella , Microbiota , Esgotos , Fósforo/metabolismo , Reatores Biológicos/microbiologia , Bactérias/metabolismo , Nutrientes
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