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1.
J Immunol ; 212(3): 397-409, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088801

RESUMO

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.


Assuntos
Coriomeningite Linfocítica , Vírus da Coriomeningite Linfocítica , Animais , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Morte Celular Programada 1/metabolismo , Exaustão das Células T
2.
Mol Cell ; 69(3): 493-504.e6, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29358080

RESUMO

Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/metabolismo , Citoplasma , Citosol , Regulação da Expressão Gênica de Plantas/genética , Homeostase , Fosforilação , Imunidade Vegetal/fisiologia , Proteínas de Plantas , Transdução de Sinais , Fatores de Transcrição
3.
Nucleic Acids Res ; 52(D1): D1508-D1518, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37897343

RESUMO

Knowledge of the collective activities of individual plants together with the derived clinical effects and targeted disease associations is useful for plant-based biomedical research. To provide the information in complement to the established databases, we introduced a major update of CMAUP database, previously featured in NAR. This update includes (i) human transcriptomic changes overlapping with 1152 targets of 5765 individual plants, covering 74 diseases from 20 027 patient samples; (ii) clinical information for 185 individual plants in 691 clinical trials; (iii) drug development information for 4694 drug-producing plants with metabolites developed into approved or clinical trial drugs; (iv) plant and human disease associations (428 737 associations by target, 220 935 reversion of transcriptomic changes, 764 and 154121 associations by clinical trials of individual plants and plant ingredients); (v) the location of individual plants in the phylogenetic tree for navigating taxonomic neighbors, (vi) DNA barcodes of 3949 plants, (vii) predicted human oral bioavailability of plant ingredients by the established SwissADME and HobPre algorithm, (viii) 21-107% increase of CMAUP data over the previous version to cover 60 222 chemical ingredients, 7865 plants, 758 targets, 1399 diseases, 238 KEGG human pathways, 3013 gene ontologies and 1203 disease ontologies. CMAUP update version is freely accessible at https://bidd.group/CMAUP/index.html.


Assuntos
Bases de Dados Factuais , Compostos Fitoquímicos , Plantas Medicinais , Humanos , Filogenia , Plantas Medicinais/química , Plantas Medicinais/classificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
4.
Nano Lett ; 24(15): 4625-4632, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38568748

RESUMO

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

5.
Nano Lett ; 24(33): 10322-10330, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39133825

RESUMO

Light-to-electricity conversion is crucial for energy harvesting and photodetection, requiring efficient electron-hole pair separation to prevent recombination. Traditional junction-based mechanisms using built-in electric fields fail in nonbarrier regions. Homogeneous material harvesting under a photovoltaic effect is appealing but is only realized in noncentrosymmetric systems via a bulk photovoltaic effect. Here we report the realization of a photovoltaic effect by employing surface acoustic waves (SAWs) to generate zero-bias photocurrent in the conventional layered semiconductor MoSe2. SAWs induce periodic modulation to electronic bands and drag the photoexcited pairs toward the traveling direction. The photocurrent is extracted from a local barrier. The separation of generation and extraction processes suppresses recombination and yields a large nonlocal photoresponse. We distinguish the acousto-electric drag and electron-hole pair separation effect by fabricating devices of different configurations. The acousto-drag photovoltaic effect, enabled by piezoelectric integration, offers an efficient light-to-electricity conversion method, independent of semiconductor crystal symmetry.

6.
Am J Physiol Cell Physiol ; 326(6): C1611-C1624, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38646789

RESUMO

The influence of SGLT-1 on perivascular preadipocytes (PVPACs) and vascular remodeling is not well understood. This study aimed to elucidate the role and mechanism of SGLT-1-mediated PVPACs bioactivity. PVPACs were cultured in vitro and applied ex vivo to the carotid arteries of mice using a lentivirus-based thermosensitive in situ gel (TISG). The groups were treated with Lv-SGLT1 (lentiviral vector, overexpression), Lv-siSGLT1 (RNA interference, knockdown), or specific signaling pathway inhibitors. Assays were conducted to assess changes in cell proliferation, apoptosis, glucose uptake, adipogenic differentiation, and vascular remodeling in the PVPACs. Protein expression was analyzed by Western blotting, immunocytochemistry, and/or immunohistochemistry. The methyl thiazolyl tetrazolium (MTT) assay and Hoechst 33342 staining indicated that SGLT-1 overexpression significantly promoted PVPACs proliferation and inhibited apoptosis in vitro. Conversely, SGLT-1 knockdown exerted the opposite effect. Oil Red O staining revealed that SGLT-1 overexpression facilitated adipogenic differentiation, while its inhibition mitigated these effects. 3H-labeled glucose uptake experiments demonstrated that SGLT-1 overexpression enhanced glucose uptake by PVPACs, whereas RNA interference-mediated SGLT-1 inhibition had no significant effect on glucose uptake. Moreover, RT-qPCR, Western blotting, and immunofluorescence analyses revealed that SGLT-1 overexpression upregulated FABP4 and VEGF-A levels and activated the Akt/mTOR/p70S6K signaling pathway, whereas SGLT-1 knockdown produced the opposite effects. In vivo studies corroborated these findings and indicated that SGLT-1 overexpression facilitated carotid artery remodeling. Our study demonstrates that SGLT-1 activation of the Akt/mTOR/p70S6K signaling pathway promotes PVPACs proliferation, adipogenesis, glucose uptake, glucolipid metabolism, and vascular remodeling.NEW & NOTEWORTHY SGLT-1 is expressed in PVPACs and can affect preadipocyte glucolipid metabolism and vascular remodeling. SGLT-1 promotes the biofunctions of PVPACs mediated by Akt/mTOR/p70S6K signaling pathway. Compared with caudal vein or intraperitoneal injection, the external application of lentivirus-based thermal gel around the carotid artery is an innovative attempt at vascular remodeling model, it may effectively avoid the transfection of lentiviral vector into the whole body of mice and the adverse effect on experimental results.


Assuntos
Adipócitos , Proliferação de Células , Proteínas Proto-Oncogênicas c-akt , Proteínas Quinases S6 Ribossômicas 70-kDa , Transdução de Sinais , Transportador 1 de Glucose-Sódio , Serina-Treonina Quinases TOR , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Camundongos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Adipócitos/metabolismo , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Masculino , Adipogenia/fisiologia , Camundongos Endogâmicos C57BL , Remodelação Vascular , Células Cultivadas , Apoptose , Diferenciação Celular , Glucose/metabolismo , Glucose/deficiência
7.
J Cell Mol Med ; 28(4): e18113, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38332530

RESUMO

The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC). Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta-like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin-2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC.


Assuntos
Anoikis , Proteínas de Ligação ao Cálcio , Neoplasias Gástricas , Humanos , Anoikis/genética , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas da Matriz Extracelular , Linhagem Celular Tumoral , Metástase Neoplásica , Integrina beta1/genética
8.
Metabolomics ; 20(3): 59, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773019

RESUMO

INTRODUCTION: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. OBJECTIVES: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). METHODS: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. RESULTS: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.


Assuntos
Biomarcadores Tumorais , Testes Respiratórios , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Microextração em Fase Sólida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Metabolômica/métodos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/metabolismo , Testes Respiratórios/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Adulto , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/metabolismo , Detecção Precoce de Câncer/métodos , Idoso
9.
Respir Res ; 25(1): 140, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528530

RESUMO

BACKGROUND: Smoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity. METHODS: We conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge. RESULTS: Among 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128). CONCLUSION: Early smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Abandono do Hábito de Fumar , Adolescente , Humanos , Adulto Jovem , Adulto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Pulmão , Prognóstico
10.
Chemistry ; 30(35): e202400566, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642049

RESUMO

The prosperity of the lithium-ion battery market is inevitably accompanied by the depletion of corresponding resources and the accumulation of spent batteries in a dialectical manner. Spent lithium-ion batteries are harboring the characteristics of hazardous waste and high-value resources, so efficient recycling is of great significance. The cathode material is considered as an interesting target for repurposing. Despite some important reviews give commendable emphasis to recycling technologies, there is still a dearth of exploration of recycling mechanisms. This deficiency of awareness highlights the need for further research and development in this area. This review aims to systematically review and thoroughly discuss the reduction reaction mechanism of each method regarding different cathode materials. And systematically digest the selection of reducing agent and the effect of reduction reaction on material regeneration are systematically digested, as well as the impact of the reduction reaction on the regeneration of materials. This review emphasizes the importance of balancing efficiency, economic and environmental benefits in reuse technologies. Finally, the review proposes an outlook on the opportunities and challenges facing the reuse of key materials for next-generation spent batteries aimed at promoting the green and sustainable development of lithium-ion batteries, circular economy and ecological balance.

11.
J Gen Intern Med ; 39(1): 69-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37620726

RESUMO

BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.


Assuntos
Adesão à Medicação , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estudos Transversais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Administração por Inalação , Fatores de Risco
12.
BMC Cancer ; 24(1): 877, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039516

RESUMO

BACKGROUND: Inetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated. METHODS: This prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. RESULTS: Forty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. CONCLUSION: Neoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment. TRIAL REGISTRATION: NCT05749016 (registration date: Nov 01, 2021).


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Carboplatina , Terapia Neoadjuvante , Pontuação de Propensão , Receptor ErbB-2 , Taxoides , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Prospectivos , Adulto , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Idoso , Trastuzumab/uso terapêutico , Trastuzumab/administração & dosagem , Resultado do Tratamento
13.
Ann Hematol ; 103(4): 1293-1303, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148345

RESUMO

Diallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria-dependent pathway and increases the levels of γ-H2AX, a DNA damage marker. Combination index (CI) measurements indicated that the combination of DADS with melphalan has a significant synergistic effect on MM cells. This was further confirmed by the increases in apoptotic cells and DNA damage in MM cells treated with the two drug combinations compared with those cells treated with a single drug alone. The synergy between DADS and melphalan was also observed in primary MM cells. Furthermore, mechanistic investigations showed that DADS decreases reduced glutathione (GSH) levels and increases reactive oxygen species (ROS) production in MM cells. The addition of GSH is effective in neutralizing DADS cytotoxicity and inhibiting the synergy between DADS and melphalan in MM cells. Taken together, our study highlights the effectiveness of DADS in treating MM cells and the promising therapeutic potential of combining DADS and melphalan for MM treatment.


Assuntos
Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Compostos Alílicos , Dissulfetos , Melfalan , Mieloma Múltiplo , Humanos , Espécies Reativas de Oxigênio , Melfalan/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Dano ao DNA , Apoptose , Combinação de Medicamentos
14.
Langmuir ; 40(21): 11039-11048, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38743262

RESUMO

The synergistic effect between bimetallic catalysts has been confirmed as an effective method for activating persulfate (PMS). Therefore, we immobilized copper-cobalt on chitosan to prepare bimetallic carbon catalysts for PMS activation and degradation of reactive dyes. Experimental results demonstrate that the CuCo-CTs/PMS catalytic degradation system exhibits excellent degradation performance toward various types of reactive dyes (e.g., Ethyl violet, Chlortalidone, and Di chlorotriazine), with degradation rates reaching 90% within 30 min. CuCo-CTs exhibit high catalytic activity over a wide pH range of 3-11 at room temperature and under static conditions, degrading over 92% of RV5 within 60 min. ultraviolet-visible (UV-vis) spectroscopy and color changes in the dye solution confirm the effective degradation of RV5, with a degradation rate of 97.2% within 10 min. Additionally, CuCo-CTs demonstrate good stability and reusability, maintaining a degradation rate of 92.8% after eight cycles. Kinetic studies indicate that the degradation follows pseudo-first-order kinetics. Furthermore, based on the results of radical scavenging experiments, the catalytic degradation mechanism of the dye involves both radical and nonradical pathways, with 1O2 identified as the primary active species. This study provides insights and experimental evidence for the application of persulfate oxidation in the treatment of dyeing wastewater.

15.
J Appl Microbiol ; 135(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39003242

RESUMO

AIMS: Developing energy-saving and ecofriendly strategies for treating harvested Microcystis biomass. METHODS AND RESULTS: Streptomyces amritsarensis HG-16 was first reported to effectively kill various morphotypes of natural Microcystis colonies at very high cell densities. Concurrently, HG-16 grown on lysed Microcystis maintained its antagonistic activity against plant pathogenic fungus Fusarium graminearum. It could completely inhibit spore germination and destroy mycelial structure of F. graminearum. Transcriptomic analysis revealed that HG-16 attacked F. graminearum in a comprehensive way: interfering with replication, transcription, and translation processes, inhibiting primary metabolisms, hindering energy production and simultaneously destroying stress-resistant systems of F. graminearum. CONCLUSIONS: The findings of this study provide a sustainable and economical option for resource reclamation from Microcystis biomass: utilizing Microcystis slurry to propagate HG-16, which can subsequently be employed as a biocontrol agent for managing F. graminearum.


Assuntos
Fusarium , Microcystis , Esporos Fúngicos , Streptomyces , Fusarium/crescimento & desenvolvimento , Fusarium/fisiologia , Streptomyces/genética , Streptomyces/fisiologia , Streptomyces/crescimento & desenvolvimento , Streptomyces/metabolismo , Microcystis/crescimento & desenvolvimento , Microcystis/genética , Microcystis/fisiologia , Esporos Fúngicos/crescimento & desenvolvimento , Antibiose
16.
J Chem Phys ; 161(8)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39171718

RESUMO

Phycocyanin 620 (PC620) is the outermost light-harvesting complex in phycobilisome of cyanobacteria, engaged in light collection and energy transfer to the core antenna, allophycocyanin. Recently, long-lived exciton-vibrational coherences have been observed in allophycocyanin, accounting for the coherent energy transfer [Zhu et al., Nat. Commun. 15, 3171 (2024)]. PC620 has a nearly identical spatial location of three α84-ß84 phycocyanobilin pigment pairs to those in allophycocyanin, inferring an existence of possible coherent energy transfer pathways. However, whether PC620 undergoes coherent or incoherent energy transfer remains debated. Furthermore, accurate determination of energy transfer rates in PC620 is still necessary owing to the spectral overlap and broadening in conventional time-resolved spectroscopic measurements. In this work, the energy transfer process within PC620 was directly resolved by polarization-controlled two dimensional electronic spectroscopy (2DES) and global analysis. The results show that the energy transfer from α84 to the adjacent ß84 has a lifetime constant of 400 fs, from ß155 to ß84 of 6-8 ps, and from ß155 to α84 of 66 ps, fully conforming to the Förster resonance energy transfer mechanism. The circular dichroism spectrum also reveals that the α84-ß84 pigment pair does not form excitonic dimer, and the observed oscillatory signals are confirmed to be vibrational coherence, excluding the exciton-vibrational coupling. Nodal line slope analysis of 2DES further reveals that all the vibrational modes participate in the energy dissipation of the excited states. Our results consolidate that the ultrafast energy transfer process in PC620 is incoherent, where the twisted conformation of α84 is suggested as the main cause for preventing the formation of α84-ß84 excitonic dimer in contrast to allophycocyanin.

17.
BMC Health Serv Res ; 24(1): 606, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38720312

RESUMO

BACKGROUND: Assisted index case testing (ICT), in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase status awareness in people living with HIV. While the available evidence from eastern and southern Africa suggests that assisted ICT can be an effective, efficient, cost-effective, acceptable, and low-risk strategy to implement in the region, it reveals that feasibility barriers to implementation exist. This study aims to inform the design of implementation strategies to mitigate these feasibility barriers by examining "assisting" health care workers' experiences of how barriers manifest throughout the assisted ICT process, as well as their perceptions of potential opportunities to facilitate feasibility. METHODS: In-depth interviews were conducted with 26 lay health care workers delivering assisted ICT in Malawian health facilities. Interviews explored health care workers' experiences counseling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted ICT. Analysis included multiple rounds of coding and iteration with the data collection team. RESULTS: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including sensitivities around discussing ICT with clients, privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, and logistical obstacles to tracing. Participants also reported several health care worker characteristics that facilitate feasibility (knowledge, interpersonal skills, non-stigmatizing attitudes and behaviors, and a sense of purpose), as well as identified process improvements with the potential to mitigate barriers. CONCLUSIONS: Maximizing assisted ICT's potential to increase status awareness in people living with HIV requires equipping health care workers with effective training and support to address and overcome the many feasibility barriers that they face in implementation. Findings demonstrate the need for, as well as inform the development of, implementation strategies to mitigate barriers and promote facilitators to feasibility of assisted ICT. TRIAL REGISTRATION: NCT05343390. Date of registration: April 25, 2022.


Assuntos
Estudos de Viabilidade , Infecções por HIV , Pesquisa Qualitativa , Humanos , Malaui , Infecções por HIV/diagnóstico , Feminino , Masculino , Adulto , Entrevistas como Assunto , Teste de HIV/métodos , Busca de Comunicante/métodos , Agentes Comunitários de Saúde
18.
BMC Musculoskelet Disord ; 25(1): 472, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880874

RESUMO

BACKGROUND: Scoliosis is a high incidence disease that endangers the physical and mental health of adolescents. Traction therapy, as a conservative treatment plan, is helpful to improve the recovery speed of patients by studying the influence of different traction factors on the therapeutic effect. METHODS: Based on the thin layer CT data of the lumbar spine of a 16-year-old patient with scoliosis, Mimics21.0 was used to extract the 3D digital model, and Geomagic Wrap2021 was used to perform the smooth surface. After that, SolidWorks was used to manually construct the structures, such as the intervertebral disc, and Ansys17.0 was used to add constraints, ligaments, and other features. Three-factor ANOVA was carried out after an orthogonal experiment that considered traction mode, traction angle, and traction force was finished. RESULTS: ① A three-dimensional biomechanical model of lumbar scoliosis was created. ② The model's correctness was confirmed by comparing it to the corpse and other finite element models, as well as by verifying it under a range of working settings. ③ Traction force (P = 0.000), traction angle (P = 0.000), the interaction between traction force and traction angle (P = 0.000), and the interaction between traction mode and traction angle (P = 0.045) were all significant. ④ The interaction between traction force and traction angle has the most significant effect on Cobb, and traction with a certain angle is better than traditional axial traction. ⑤ Traction mode is not significant, but the interaction between traction mode and traction angle is significant. CONCLUSIONS: A certain angle of traction can aid in improving outcomes and the traction force can be suitably decreased in the clinical formulation of the traction plan. The uniformity of correcting effect is more favorable when higher fixation techniques like positive suspension or traction bed traction are used, as opposed to overhanging traction.


Assuntos
Análise de Elementos Finitos , Vértebras Lombares , Escoliose , Tração , Humanos , Tração/métodos , Escoliose/terapia , Escoliose/diagnóstico por imagem , Escoliose/fisiopatologia , Vértebras Lombares/diagnóstico por imagem , Adolescente , Imageamento Tridimensional , Fenômenos Biomecânicos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Chem Soc Rev ; 52(13): 4132-4148, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37314457

RESUMO

As an economical solar energy conversion technology, organic photovoltaics (OPVs) are regarded as a promising solution to environmental problems and energy challenges. With the highest efficiency of OPVs exceeding 20%, the research focus will shift from efficiency-oriented aspects to commercialization-oriented aspects in the near future. Semi-transparent OPVs (STOPVs) are one of the most possible commercialized forms of OPVs, and have achieved power conversion efficiency over 14% with average visible light transmittance over 20% so far. In this tutorial review, we first systematically summarize the device structures, operating principles and evaluation parameters of STOPVs, and compare them with those of opaque OPVs. Then, strategies to construct high-performance STOPVs by cooperatively optimizing materials and devices are proposed. Methods to realize the scale-up of STOPVs in terms of minimization of electrode and interconnect resistance are summarized. The potential applications of STOPVs in multifunctional windows, agrivoltaics and floating photovoltaics are also discussed. Finally, this review highlights major challenges and research directions that need to be addressed prior to the future commercialization of STOPVs.

20.
Sensors (Basel) ; 24(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38544067

RESUMO

Perception plays a crucial role in ensuring the safety and reliability of autonomous driving systems. However, the recognition and localization of small objects in complex scenarios still pose challenges. In this paper, we propose a point cloud object detection method based on dynamic sparse voxelization to enhance the detection performance of small objects. This method employs a specialized point cloud encoding network to learn and generate pseudo-images from point cloud features. The feature extraction part uses sliding windows and transformer-based methods. Furthermore, multi-scale feature fusion is performed to enhance the granularity of small object information. In this experiment, the term "small object" refers to objects such as cyclists and pedestrians, which have fewer pixels compared to vehicles with more pixels, as well as objects of poorer quality in terms of detection. The experimental results demonstrate that, compared to the PointPillars algorithm and other related algorithms on the KITTI public dataset, the proposed algorithm exhibits improved detection accuracy for cyclist and pedestrian target objects. In particular, there is notable improvement in the detection accuracy of objects in the moderate and hard quality categories, with an overall average increase in accuracy of about 5%.

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