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1.
Cell Rep Med ; 5(2): 101399, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38307032

RESUMO

Colorectal cancer (CRC) is a common malignancy involving multiple cellular components. The CRC tumor microenvironment (TME) has been characterized well at single-cell resolution. However, a spatial interaction map of the CRC TME is still elusive. Here, we integrate multiomics analyses and establish a spatial interaction map to improve the prognosis, prediction, and therapeutic development for CRC. We construct a CRC immune module (CCIM) that comprises FOLR2+ macrophages, exhausted CD8+ T cells, tolerant CD8+ T cells, exhausted CD4+ T cells, and regulatory T cells. Multiplex immunohistochemistry is performed to depict the CCIM. Based on this, we utilize advanced deep learning technology to establish a spatial interaction map and predict chemotherapy response. CCIM-Net is constructed, which demonstrates good predictive performance for chemotherapy response in both the training and testing cohorts. Lastly, targeting FOLR2+ macrophage therapeutics is used to disrupt the immunosuppressive CCIM and enhance the chemotherapy response in vivo.


Assuntos
Neoplasias Colorretais , Aprendizado Profundo , Receptor 2 de Folato , Humanos , Linfócitos T CD8-Positivos , Multiômica , Macrófagos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Microambiente Tumoral/genética
2.
Neuron ; 111(14): 2201-2217.e4, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37172583

RESUMO

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.


Assuntos
Colecistocinina , Relógios Circadianos , Animais , Camundongos , Ritmo Circadiano/fisiologia , Mamíferos/metabolismo , Neurônios/fisiologia , Fotoperíodo , Núcleo Supraquiasmático/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
3.
Molecules ; 28(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36770890

RESUMO

As an essential trace element in the human body, selenium (Se) has various physiological activities, such as antioxidant and anticancer activity. Selenium-enriched proteins/peptides (SePs/SePPs) are the primary forms of Se in plants and animals, and they are the vital carriers of its physiological activities. On the basis of current research, this review systematically describes the extraction methods (aqueous, alkaline, enzymatic, auxiliary, etc.) and detection methods (HPLC-MS/MS, GC-ICP-MS, etc.) for SePs/SePPs in plants. Their bioavailability and bioactivity, and the effect of processing are also included. Our review provides a comprehensive understanding and theoretical guidance for the utilization of selenium-enriched proteins/peptides.


Assuntos
Selênio , Animais , Humanos , Proteínas de Plantas , Espectrometria de Massas em Tandem , Disponibilidade Biológica , Peptídeos , Plantas
4.
Foods ; 11(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35563923

RESUMO

Selenium (Se) biofortification during seed germination is important not only to meet nutritional demands but also to prevent Se-deficiency-related diseases by producing Se-enriched foods. In this study, we evaluated effects of Se biofortification of soybeans on the Se concentration, speciation, and species transformation as well as nutrients and bioactive compounds in sprouts during germination. Soybean (Glycine max L.) seedlings were cultivated in the dark in an incubator with controlled temperature and water conditions and harvested at different time points after soaking in Se solutions (0, 5, 10, 20, 40, and 60 mg/L). Five Se species and main nutrients in the sprouts were determined. The total Se content increased by 87.3 times, and a large portion of inorganic Se was transformed into organic Se during 24 h of germination, with 89.3% of the total Se was bound to soybean protein. Methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were the dominant Se species, MeSeCys decreased during the germination, but SeMet had opposite trend. Se biofortification increased contents of total polyphenol and isoflavonoid compounds and amino acids (both total and essential), especially in low-concentration Se treatment. In conclusion, Se-enriched soybean sprouts have promising potential for Se supplementation and as functional foods.

5.
Materials (Basel) ; 15(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408035

RESUMO

The composite-material laminate structure will inevitably encounter connection problems in use. Among them, mechanical connections are widely used in aerospace, automotive and other fields because of their high connection efficiency and reliable connection performance. Milling parameters are important for the opening quality. In this paper, continuous-glass-fiber-reinforced-polypropylene (GFRPP) laminates were chosen to investigate the effects of different cutters and process parameters on the hole quality. The delamination factor and burr area were taken as the index to characterize the opening quality. After determining the optimal milling tool, the process window was obtained according to the appearance of the milling hole. In the selected process parameter, the maximum temperature did not reach the PP melting temperature. The best hole quality was achieved when the spindle speed was 18,000 r/min and the feed speed was 1500 mm/min with the corn milling cutter.

6.
Inorg Chem ; 60(12): 8456-8460, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34085808

RESUMO

A flexible and robust microporous copper(II) metal-organic framework (MOF) based on a methyl-functionalized ligand, namely, [Cu3(µ3-OH)2(L)2(DMF)] (LIFM-ZZ-1; L = 2,2'-dimethyl-4,4'-biphenyldicarboxylic acid and DMF = N,N-dimethylformamide), was constructed. Its sorption performance for the separation of CH4, C2H6, and C3H8 was investigated. LIFM-ZZ-1 showed a breathing behavior that led to a transition between large- and narrow-pore states. The sample also showed outstanding water stability. Gas adsorption experiments revealed that desolvated LIFM-ZZ-1 exhibited higher adsorption capacities for C2H6 and C3H8 (2.80 and 4.06 mmol·g-1) than for CH4 (0.39 mmol·g-1) at 298 K and 1 bar. Breakthrough experiments showed that a CH4/C2H6/C3H8 mixture was completely separated at 298 K, demonstrating the promising potential applications of this material for separating low contents of C2/C3 hydrocarbons from natural gas.

7.
Ann Transl Med ; 9(8): 639, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987337

RESUMO

BACKGROUND: What features should alert clinicians to suspect underlying tumors in patients with acute pancreatitis (AP) was largely unknown. This study aimed to assess the clinical characteristics and outcome in patients with tumor-associated AP. METHODS: Patients who presented with AP and were diagnosed with tumor after admission were included according to the inclusion and exclusion criteria and followed up by hospital notes, telephone, WeChat and/or e-mail. The clinical characteristics and outcome were analyzed with multivariable logistic regression and were compared with AP patients without tumor. RESULTS: Out of a cohort of 1,792 AP patients we identified 103 who had a neoplastic etiology. The 103 patients had a median age of 57 (range, 13-81) and 65 were males. AP was mild in 92 patients, moderately severe in 7 and severe in 4. The three most common tumors included pancreatic cancer (PC) (40), periampullary carcinoma (PAC) (25), and neoplastic pancreatic cysts (NPC) (22). The following ranked features were predictive of a tumor etiology: dilation of main pancreatic duct (MPD) (OR 417.83, 95% CI: 80.40-2,171.42), vascular invasion (OR 82.04, 95% CI: 6.05-1,113.14), mild AP (8.29, 95% CI: 1.98-34.73), and anemia (OR 5.73, 95% CI: 2.02-16.26). The median survival period of AP patients with PC, PAC, and NPC was 10.0 (7.0-23.5), 21.0 (5.0-37.0), and 35.0 (30.0-96.0) months, respectively. CONCLUSIONS: Mild AP patients with dilation of MPD, vascular invasion, and anemia were more frequently suggested a tumor etiology. Thus, clinical vigilance is needed for timely detection of tumor-associated pancreatitis with these characteristics.

8.
Clin Rheumatol ; 35(5): 1145-51, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26809798

RESUMO

We evaluated clinical characteristics and prognosis for adult-onset Still's disease (AOSD) complicated by hemophagocytic lymphohistiocytosis (HLH). We retrospectively identified cases of AOSD with (n = 10) and without (n = 305) HLH complications. We reviewed their medical records, completed follow-up through outpatient clinic and telephone interviews, and analyzed their clinical symptoms, signs, laboratory test results, treatments, and prognosis. More AOSD patients with HLH developed hepatomegaly, bleeding, serositis, and neurologic symptoms than those without HLH, and they more commonly presented with leukopenia, thrombocytopenia, severe anemia, severe liver function abnormalities, decreased fibrinogen, elevated immunoglobulin, and bone marrow hemophagocytosis. The ten patients with AOSD complicated by HLH were treated with high-dose steroids or pulse steroid therapy, and eight of them also received cytotoxic drugs, while biological agents showed poor response. Follow-up results indicated that AOSD patients overall had good prognosis, while those with HLH showed worse prognosis, including higher relapse and readmission rates and increased mortality. In patients with AOSD, unexplained decreased blood cells, severe liver dysfunction, and/or hemophagocytosis in the bone marrow should be considered as signs of HLH complication. Patients with AOSD complicated by HLH have worse prognosis and higher relapse rates compared to AOSD patients without HLH complications. Thus, these patients should undergo frequent and careful follow-up.


Assuntos
Linfo-Histiocitose Hemofagocítica/complicações , Doença de Still de Início Tardio/diagnóstico , Adolescente , Adulto , Idoso , Anemia/complicações , Feminino , Glucocorticoides/uso terapêutico , Humanos , Leucopenia/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/tratamento farmacológico , Avaliação de Sintomas , Trombocitopenia/complicações , Adulto Jovem
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