Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 108
Filtrar
2.
Adv Mater ; : e2310480, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669281

RESUMO

Conjugated polymers are promising materials for thermoelectric applications, however, at present few effective and well-understood strategies exist to further advance their thermoelectric performance. Here a new model system is reported for a better understanding of the key factors governing their thermoelectric properties: aligned, ribbon-phase poly[2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT) doped by ion-exchange doping. Using a range of microstructural and spectroscopic methods, the effect of controlled incorporation of tie-chains between the crystalline domains is studied through blending of high and low molecular weight chains. The tie chains provide efficient transport pathways between crystalline domains and lead to significantly enhanced electrical conductivity of 4810 S cm-1, which is not accompanied by a reduction in Seebeck coefficient or a large increase in thermal conductivity. Respectable power factors of 173 µW m-1 K-2 are demonstrated in this model system. The approach is generally applicable to a wide range of semicrystalline conjugated polymers and could provide an effective pathway for further enhancing their thermoelectric properties and overcome traditional trade-offs in optimization of thermoelectric performance.

3.
Discov Ment Health ; 4(1): 11, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573526

RESUMO

The clinical burden of mental illness, in particular schizophrenia and bipolar disorder, are driven by frequent chronic courses and increased mortality, as well as the risk for comorbid conditions such as cardiovascular disease and type 2 diabetes. Evidence suggests an overlap of molecular pathways between psychotic disorders and somatic comorbidities. In this study, we developed a computational framework to perform comorbidity modeling via an improved integrative unsupervised machine learning approach based on multi-rank non-negative matrix factorization (mrNMF). Using this procedure, we extracted molecular signatures potentially explaining shared comorbidity mechanisms. For this, 27 case-control microarray transcriptomic datasets across multiple tissues were collected, covering three main categories of conditions including psychotic disorders, cardiovascular diseases and type II diabetes. We addressed the limitation of normal NMF for parameter selection by introducing multi-rank ensembled NMF to identify signatures under various hierarchical levels simultaneously. Analysis of comorbidity signature pairs was performed to identify several potential mechanisms involving activation of inflammatory response auxiliarily interconnecting angiogenesis, oxidative response and GABAergic neuro-action. Overall, we proposed a general cross-cohorts computing workflow for investigating the comorbid pattern across multiple symptoms, applied it to the real-data comorbidity study on schizophrenia, and further discussed the potential for future application of the approach.

4.
Nature ; 628(8009): 765-770, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658685

RESUMO

Solar fuels offer a promising approach to provide sustainable fuels by harnessing sunlight1,2. Following a decade of advancement, Cu2O photocathodes are capable of delivering a performance comparable to that of photoelectrodes with established photovoltaic materials3-5. However, considerable bulk charge carrier recombination that is poorly understood still limits further advances in performance6. Here we demonstrate performance of Cu2O photocathodes beyond the state-of-the-art by exploiting a new conceptual understanding of carrier recombination and transport in single-crystal Cu2O thin films. Using ambient liquid-phase epitaxy, we present a new method to grow single-crystal Cu2O samples with three crystal orientations. Broadband femtosecond transient reflection spectroscopy measurements were used to quantify anisotropic optoelectronic properties, through which the carrier mobility along the [111] direction was found to be an order of magnitude higher than those along other orientations. Driven by these findings, we developed a polycrystalline Cu2O photocathode with an extraordinarily pure (111) orientation and (111) terminating facets using a simple and low-cost method, which delivers 7 mA cm-2 current density (more than 70% improvement compared to that of state-of-the-art electrodeposited devices) at 0.5 V versus a reversible hydrogen electrode under air mass 1.5 G illumination, and stable operation over at least 120 h.

5.
Biochim Biophys Acta Gen Subj ; 1868(5): 130592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395204

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression. METHODS: The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1. RESULTS: The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter. CONCLUSION: AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis. GENERAL: Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , alfa-Fetoproteínas/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Fatores de Transcrição de Domínio TEA
6.
Small ; : e2310199, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38063859

RESUMO

Solution-processable near-infrared (NIR) photodetectors are urgently needed for a wide range of next-generation electronics, including sensors, optical communications and bioimaging. However, it is rare to find photodetectors with >300 kHz cut-off frequencies, especially in the NIR region, and many of the emerging inorganic materials explored are comprised of toxic elements, such as lead. Herein, solution-processed AgBiS2 photodetectors with high cut-off frequencies under both white light (>1 MHz) and NIR (approaching 500 kHz) illumination are developed. These high cut-off frequencies are due to the short transit distances of charge-carriers in the ultrathin photoactive layer of AgBiS2 photodetectors, which arise from the strong light absorption of this material, such that film thicknesses well below 120 nm are sufficient to absorb >65% of NIR to visible light. It is also revealed that ion migration plays a critical role in the photo-response speed of these devices, and its detrimental effects can be mitigated by finely tuning the thickness of the photoactive layer, which is important for achieving low dark current densities as well. These outstanding characteristics enable the realization of air-stable, real-time heartbeat sensors based on NIR AgBiS2 photodetectors, which strongly motivates their future integration in high-throughput systems.

7.
Adv Sci (Weinh) ; 10(36): e2302494, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37985839

RESUMO

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.


Assuntos
Neoplasias , Reparo de DNA por Recombinação , Humanos , Reparo de DNA por Recombinação/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Reparo do DNA/genética , Neoplasias/tratamento farmacológico , Coesinas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
8.
Small Methods ; 7(11): e2300476, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37661594

RESUMO

Organic semiconductors are a family of pi-conjugated compounds used in many applications, such as displays, bioelectronics, and thermoelectrics. However, their susceptibility to processing-induced contamination is not well understood. Here, it is shown that many organic electronic devices reported so far may have been unintentionally contaminated, thus affecting their performance, water uptake, and thin film properties. Nuclear magnetic resonance spectroscopy is used to detect and quantify contaminants originating from the glovebox atmosphere and common laboratory consumables used during device fabrication. Importantly, this in-depth understanding of the sources of contamination allows the establishment of clean fabrication protocols, and the fabrication of organic field effect transistors (OFETs) with improved performance and stability. This study highlights the role of unintentional contaminants in organic electronic devices, and demonstrates that certain stringent processing conditions need to be met to avoid scientific misinterpretation, ensure device reproducibility, and facilitate performance stability. The experimental procedures and conditions used herein are typical of those used by many groups in the field of solution-processed organic semiconductors. Therefore, the insights gained into the effects of contamination are likely to be broadly applicable to studies, not just of OFETs, but also of other devices based on these materials.

9.
J Am Chem Soc ; 145(39): 21330-21343, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37738152

RESUMO

The family of hybrid organic-inorganic lead-halide perovskites are the subject of intense interest for optoelectronic applications, from light-emitting diodes to photovoltaics to X-ray detectors. Due to the inert nature of most organic molecules, the inorganic sublattice generally dominates the electronic structure and therefore the optoelectronic properties of perovskites. Here, we use optically and electronically active carbazole-based Cz-Ci molecules, where Ci indicates an alkylammonium chain and i indicates the number of CH2 units in the chain, varying from 3 to 5, as cations in the two-dimensional (2D) perovskite structure. By investigating the photophysics and charge transport characteristics of (Cz-Ci)2PbI4, we demonstrate a tunable electronic coupling between the inorganic lead-halide and organic layers. The strongest interlayer electronic coupling was found for (Cz-C3)2PbI4, where photothermal deflection spectroscopy results remarkably reveal an organic-inorganic charge transfer state. Ultrafast transient absorption spectroscopy measurements demonstrate ultrafast hole transfer from the photoexcited lead-halide layer to the Cz-Ci molecules, the efficiency of which increases by varying the chain length from i = 5 to i = 3. The charge transfer results in long-lived carriers (10-100 ns) and quenched emission, in stark contrast to the fast (sub-ns) and efficient radiative decay of bound excitons in the more conventional 2D perovskite (PEA)2PbI4, in which phenylethylammonium (PEA) acts as an inert spacer. Electrical charge transport measurements further support enhanced interlayer coupling, showing increased out-of-plane carrier mobility from i = 5 to i = 3. This study paves the way for the rational design of 2D perovskites with combined inorganic-organic electronic properties through the wide range of functionalities available in the world of organics.

10.
Adv Sci (Weinh) ; 10(29): e2303837, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37551064

RESUMO

n-Type organic electrochemical transistors (OECTs) and organic field-effect transistors (OFETs) are less developed than their p-type counterparts. Herein, polynaphthalenediimide (PNDI)-based copolymers bearing novel fluorinated selenophene-vinylene-selenophene (FSVS) units as efficient materials for both n-type OECTs and n-type OFETs are reported. The PNDI polymers with oligo(ethylene glycol) (EG7) side chains P(NDIEG7-FSVS), affords a high µC* of > 0.2 F cm-1  V-1  s-1 , outperforming the benchmark n-type Pg4NDI-T2 and Pg4NDI-gT2 by two orders of magnitude. The deep-lying LUMO of -4.63 eV endows P(NDIEG7-FSVS) with an ultra-low threshold voltage of 0.16 V. Moreover, the conjugated polymer with octyldodecyl (OD) side chains P(NDIOD-FSVS) exhibits a surprisingly low energetic disorder with an Urbach energy of 36 meV and an ultra-low activation energy of 39 meV, resulting in high electron mobility of up to 0.32 cm2  V-1  s-1 in n-type OFETs. These results demonstrate the great potential for simultaneously achieving a lower LUMO and a tighter intermolecular packing for the next-generation efficient n-type organic electronics.

11.
Environ Sci Pollut Res Int ; 30(37): 87669-87684, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37430080

RESUMO

Food waste (FW) treatment has attracted increasing attention since waste classification occurred in China. Analyzing the environmental and economic impacts of different FW treatment technologies is required. In this study, four FW treatments, i.e., anaerobic digestion, black soldier fly (BSF) bioconversion, composting, and landfill, were evaluated using life cycle assessment (LCA) and life cycle cost (LCC). LCA results show that anaerobic digestion outperforms the other technologies, while LCC results indicate anaerobic digestion has the lowest economic benefits ($5.16) and landfill has the highest ($14.22). Bioconversion has the highest product revenue ($37.98). FW anaerobic digestion followed by treating digestate and waste crude oil was employed to investigate the environmental differences between waste classification and mixed incineration. Digestate gasification and conversion of waste crude oil to biodiesel are found to be environmentally friendly, and waste classification outperforms mixed incineration. Furthermore, we explored national-level environmental emission reduction with anaerobic digestion as the dominant technology via increasing resource utilization rate and applying household FW disposers. Results display that a 60% resource utilization rate decreases the overall environmental impact by 36.68% compared with current situation, and treating household FW separately at the source can further lead to emission reduction. This study provides a reference for selecting FW technologies for countries worldwide from environmental and economic perspectives, as well as a direction of resource utilization for how to reduce environmental emissions from treating the total FW produced by all humanity.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Animais , Alimentos , China , Estágios do Ciclo de Vida
12.
Small ; 19(41): e2302494, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37300316

RESUMO

The migration of ionic defects and electrochemical reactions with metal electrodes remains one of the most important research challenges for organometal halide perovskite optoelectronic devices. There is still a lack of understanding of how the formation of mobile ionic defects impact charge carrier transport and operational device stability, particularly in perovskite field-effect transistors (FETs), which tend to exhibit anomalous device characteristics. Here, the evolution of the n-type FET characteristics of one of the most widely studied materials, Cs0.05 FA0.17 MA0.78 PbI3, is investigated during repeated measurement cycles as a function of different metal source-drain contacts and precursor stoichiometry. The channel current increases for high work function metals and decreases for low work function metals when multiple cycles of transfer characteristics are measured. The cycling behavior is also sensitive to the precursor stoichiometry. These metal/stoichiometry-dependent device non-idealities are correlated with the quenching of photoluminescence near the positively biased electrode. Based on elemental analysis using electron microscopy the observations can be understood by an n-type doping effect of metallic ions that are created by an electrochemical interaction at the metal-semiconductor interface and migrate into the channel. The findings improve the understanding of ion migration, contact reactions, and the origin of non-idealities in lead triiodide perovskite FETs.

13.
Front Immunol ; 14: 1136343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275867

RESUMO

Objective: Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377. Results: Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data. Conclusion: A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/terapia , Transplante de Microbiota Fecal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fezes , Microbioma Gastrointestinal/fisiologia
14.
Sci Adv ; 9(22): eadg8659, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37267357

RESUMO

Organic thin-film transistors (OTFTs) with ideal behavior are highly desired, because nonideal devices may overestimate the intrinsic property and yield inferior performance in applications. In reality, most polymer OTFTs reported in the literature do not exhibit ideal characteristics. Supported by a structure-property relationship study of several low-disorder conjugated polymers, here, we present an empirical selection rule for polymer candidates for textbook-like OTFTs with high reliability factors (100% for ideal transistors). The successful candidates should have low energetic disorder along their backbones and form thin films with spatially uniform energetic landscapes. We demonstrate that these requirements are satisfied in the semicrystalline polymer PffBT4T-2DT, which exhibits a reliability factor (~100%) that is exceptionally high for polymer devices, rendering it an ideal candidate for OTFT applications. Our findings broaden the selection of polymer semiconductors with textbook-like OTFT characteristics and would shed light upon the molecular design criteria for next-generation polymer semiconductors.

16.
Acta Biochim Biophys Sin (Shanghai) ; 55(4): 633-648, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36916297

RESUMO

Ginsenoside Rh2, which is extracted from ginseng, exerts antitumor activity. Recent studies suggest that Rh2 may suppress the growth of colon cancer (CC) in vitro. However, the underlying mechanism remains unclear. In this study, we identified the relative levels of miR-150-3p in CC tissues and cells by a comprehensive strategy of data mining, computational biology, and real-time reverse transcription PCR (qRT-PCR) experiments. The regulatory effects of miR-150-3p/SRCIN1 on the proliferative and invasive abilities of CC cells are evaluated by CCK-8, EdU, wound healing, and transwell assays. Cell cycle- and apoptosis-related protein levels are assessed by western blot analysis. An in vivo tumor formation assay was conducted to explore the effects of miR-150-3p on tumor growth. Furthermore, bioinformatics and dual luciferase reporter assays are applied to determine the functional binding of miRNA to mRNA of the target gene. Finally, the relationship between Rh2 and miR-150-3p was further verified in SW620 and HCT-116 cells. miR-150-3p is downregulated in CC tissues and cell lines. Functional assays indicate that the upregulation of miR-150-3p inhibits tumor growth both in vivo and in vitro. In addition, SRCIN1 is upregulated in CC and predicts a poor prognosis, and it is the direct target for miR-150-3p. Moreover, the miR-150-3p mimic decreases Topflash/Fopflash-dependent luciferase activity, resulting in the inhibition of Wnt pathway activity. Rh2 can suppress the growth of CC by increasing miR-150-3p expression. Rh2 alleviates the accelerating effect on Wnt pathway activity, cell proliferation/migration, and colony formation caused by miR-150-3p inhibition. Rh2 inhibits the miR-150-3p/SRCIN1/Wnt axis to suppress colon cancer growth.


Assuntos
Neoplasias do Colo , Ginsenosídeos , MicroRNAs , Humanos , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Ginsenosídeos/farmacologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular
17.
Nature ; 615(7954): 830-835, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922588

RESUMO

Perovskite light-emitting diodes (LEDs) have attracted broad attention due to their rapidly increasing external quantum efficiencies (EQEs)1-15. However, most high EQEs of perovskite LEDs are reported at low current densities (<1 mA cm-2) and low brightness. Decrease in efficiency and rapid degradation at high brightness inhibit their practical applications. Here, we demonstrate perovskite LEDs with exceptional performance at high brightness, achieved by the introduction of a multifunctional molecule that simultaneously removes non-radiative regions in the perovskite films and suppresses luminescence quenching of perovskites at the interface with charge-transport layers. The resulting LEDs emit near-infrared light at 800 nm, show a peak EQE of 23.8% at 33 mA cm-2 and retain EQEs more than 10% at high current densities of up to 1,000 mA cm-2. In pulsed operation, they retain EQE of 16% at an ultrahigh current density of 4,000 mA cm-2, along with a high radiance of more than 3,200 W s-1 m-2. Notably, an operational half-lifetime of 32 h at an initial radiance of 107 W s-1 m-2 has been achieved, representing the best stability for perovskite LEDs having EQEs exceeding 20% at high brightness levels. The demonstration of efficient and stable perovskite LEDs at high brightness is an important step towards commercialization and opens up new opportunities beyond conventional LED technologies, such as perovskite electrically pumped lasers.

18.
Immunol Invest ; 52(3): 343-363, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36762677

RESUMO

BACKGROUND: Programmed death ligand 1 (PD-L1) is expressed in hepatocellular carcinoma (HCC) cells. PD-L1 function and structure are regulated through glycosylation and various signaling pathways. However, the relationship between Pseudomonas aeruginosa mannose sensitive hemagglutinin (PA-MSHA), glycosylation and PD-L1 warrants further study. In this study, we investigated the effects of PA-MSHA on the regulation of mannosyl and N-glycosylation to identify the mechanisms underlying its function. METHODS: PD-L1, ß-catenin, c-Myc, mannosyl, MGAT1 and mannosidase II in HCC were identified by postoperative specimens from the HCC cohort with immunohistochemistry and immunofluorescence. PA-MSHA was used to suppress tumor progression. Alterations to the expression of PD-L1, ß-catenin, c-Myc, MGAT1, and mannosidase II at the gene and protein levels were detected by qRT-PCR and Western blot analysis. Soluble PD-L1 (sPD-L1) were detected using enzyme-linked immunosorbent assay. RESULTS: Mannosyl and mannosidase II expression levels increased, whereas those of MGAT1 decreased in the HCC cells. The glycosylation-related pathway proteins, namely, ß-catenin, c-Myc and PD-L1, had increased expression levels. Moreover, proliferation in the HCC cells was inhibited after PA-MSHA treatment, PD-L1 function was significantly inhibited. Transmission electron microscopy showed that PA-MSHA penetrated into the HCC cytoplasm through the cytomembrane, resulting in apoptosis. Here, PA-MSHA significantly reduced sPD-L1 expression levels in the tumor cells. CONCLUSIONS: PA-MSHA plays the role of a lectin, affecting receptors on the cytomembrane. This strain inhibits mannosyl by suppressing ß-catenin signaling. We hypothesized that PA-MSHA suppresses PD-L1 by: 1. Inhibiting the glycosylation process; and 2. Suppressing ß-catenin and c-Myc, thereby reducing the transcription of this protein.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Pseudomonas aeruginosa , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Animais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Xenoenxertos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/fisiologia , Transplante de Neoplasias , Glicosilação , Transdução de Sinais , Imunoterapia , Lectinas/metabolismo
19.
J Clin Med ; 12(3)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36769385

RESUMO

BACKGROUND: Immune-related adverse events (irAEs) are side effects that reflect the activation of patients' immune systems after treatment with immune checkpoint inhibitors (ICIs). However, there is no meta-analysis on the effect of early irAEs on patient survival. Thus, we assessed the association between early irAEs and the survival of patients treated with ICIs. METHODS: PubMed, Embase, and Web of Science were searched from May 2010 to May 2020 for all the retrospective and prospective comparative studies to evaluate the hazard ratios (HRs) for death. A random-effects model was used to calculate the pooled HR for death, and heterogeneity was assessed using I² statistics. The main outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 11 reports with 2077 patients were included. A significant association was observed between early irAEs and a favorable clinical outcome. Patients with early irAEs had prolonged OS (HR: 0.62, 95% confidence interval (CI): 0.53-0.74, p < 0.001) and PFS (HR: 0.53, 95% CI: 0.41-0.66, p < 0.001) compared to those without; these results were confirmed using a sensitivity analysis. The irAE types, malignancy types, and sample size were correlated with patients' clinical outcomes. CONCLUSIONS: Early irAEs, especially cutaneous irAEs, correlated with a better clinical outcome in patients treated with ICIs.

20.
Pathol Oncol Res ; 29: 1610893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741965

RESUMO

Background: Gastric cancer (GC) is one of the global malignant tumors with high incidence and poor prognosis. Exploring new GC molecular markers is important to improve GC prognosis. Transmembrane protein 200A (TMEM200A) is a member of the family of transmembrane proteins (TMEM). This study is the first to investigate the potential function of TMEM200A and its relationship with immune infiltration in GC. Methods: The differential expression of TMEM200A was determined through the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC) curve was drawn to assess the diagnostic value of TMEM200A for GC. The relationship between TMEM200A and the clinical characteristics of patients with GC was investigated using the Wilcoxon test and the Kruskal-Wallis test. The effect of TMEM200A on overall survival (OS) was identified using the Kaplan-Meier method, the Log-rank test, the univariate/multivariate Cox regression analysis, and the nomogram prediction model. The co-expressed genes and gene set enrichment analysis (GSEA) were used to explore the potential biological functions of TMEM200A. We used the Tumor Immune Estimation Resource (TIMER) database and the ssGSEA algorithm to estimate the relationship between TMEM200A and immune cell infiltration. Furthermore, we investigated the correlation of TMEM200A with immune checkpoint/immune cell surface markers using the TCGA-STAD data set. Finally, we identified prognosis-related methylation sites in TMEM200A using MethSurv. Results: TMEM200A was highly expressed in GC tissues. TMEM200A had a good diagnostic value for GC. High expression of TMEM200A may shorten the OS of GC patients and may be an independent risk factor for OS in GC patients. TMEM200A participates in the construction of a predictive model with a good predictive effect on the survival rate of GC patients at 1, 3, and 5 years. Co-expressed genes and GSEA indicated that TMEM200A may be an adhesion molecule closely associated with tumor invasion and metastasis. In addition, TMEM200A may be significantly associated with immune cell infiltration and immune checkpoint expression. We also found that TMEM200A contains three methylation sites associated with a poor prognosis. Conclusion: Upregulated TMEM200A may be a promising prognostic marker for GC and is closely associated with the tumor microenvironment (TME).


Assuntos
Proteínas de Membrana , Neoplasias Gástricas , Humanos , Algoritmos , Bases de Dados Factuais , Proteínas de Membrana/genética , Análise Multivariada , Prognóstico , Neoplasias Gástricas/genética , Microambiente Tumoral/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...