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BACKGROUND: To elucidate the role of Mucin1 (MUC1) in the trophoblast function (glucose uptake and apoptosis) of gestational diabetes mellitus (GDM) women through the Wnt/ß-catenin pathway. METHODS: Glucose uptake was analyzed by plasma GLUT1 and GLUT4 levels with ELISA and measured by the expression of GLUT4 and INSR with immunofluorescence and Western blotting. Apoptosis was measured by the expression of Bcl-2 and Caspase3 by Western blotting and flow cytometry. Wnt/ß-catenin signaling measured by Western blotting. In vitro studies were performed using HTR-8/SVneo cells that were cultured and treated with high glucose (HG), sh-MUC1 and FH535 (inhibitor of Wnt/ß-catenin signaling). RESULTS: MUC1 was highly expressed in the placental trophoblasts of GDM, and the Wnt/ß-catenin pathway was activated, along with dysfunction of glucose uptake and apoptosis. MUC1 knockdown resulted in increased invasiveness and decreased apoptosis in trophoblast cells. The initial linkage between MUC1, the Wnt/ß-catenin pathway, and glucose uptake was confirmed by using an HG-exposed HTR-8/SVneo cell model with MUC1 knockdown. MUC1 knockdown inhibited the Wnt/ß-catenin signaling pathway and reversed glucose uptake dysfunction and apoptosis in HG-induced HTR-8/SVneo cells. Meanwhile, inhibition of Wnt/ß-catenin signaling could also reverse the dysfunction of glucose uptake and apoptosis. CONCLUSIONS: In summary, the increased level of MUC1 in GDM could abnormally activate the Wnt/ß-catenin signaling pathway, leading to trophoblast dysfunction, which may impair glucose uptake and induce apoptosis in placental tissues of GDM women.

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Influenza is an infectious acute respiratory disease with complications and a high mortality rate; the effective medicines for influenza therapy are limited. "Huanglian" or Coptidis Rhizoma, Coptis chinensis Franch., Ranunculaceae, and "ganjiang" or Zingiberis Rhizoma, Zingiber officinale Roscoe, Zingiberaceae, combination is clinically used for treating respiratory diseases. HPLC was applied for the quantification of berberine hydrochloride (1.101 mg/ml) and 6-gingerol (38.41 µg/ml) in the H2O-soluble extract of the herbal formulation. In this study, the effect of "huanglian"- "ganjiang" extract on influenza virus H1N1-induced acute pulmonary inflammation was evaluated, in addition to the investigation of its anti-influenza mechanism in a mouse model. The analyzed herbal combination inhibited the expression of cytokine IL-6 and stimulated the expression of IL-2 in the serum of influenza virus-infected mice. Meanwhile, the herbal combination downregulated the gene and protein expression levels of TLR3, TLR7, MyD88, RIG-I, MAVS, TRAF3, and NF-κB p65, which are key targets of toll-like and RIG-I-like receptor signaling pathways in mice. In addition, the herbal combination could also promote the combination of intracellular autophagosomes and lysosomes in autophagosome-lysosome formation and improve impaired fusion of autophagosomes and lysosomes by influenza virus. This study suggested that the "huanglian"- "ganjiang" extract may be a candidate therapeutic strategy for the treatment of H1N1 influenza. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00372-z.

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High heterogeneity of lung adenocarcinoma (LUAD) is a major clinical challenge. This study aims to characterize the molecular features of LUAD through classification based on metabolism-related genes. A total of 500 LUAD samples from The Cancer Genome Atlas (TCGA) and 612 from Gene Expression Omnibus (GEO) were integrated with 2,753 metabolism-related genes to determine the molecular classification. Systematic bioinformatics analysis was used to conduct correlation analysis between metabolism-related classification and molecular characteristics of LUAD. LUAD patients were divided into three molecular clusters (C1-C3). Survival analysis revealed that C1 and C2 showed good and poor prognoses, respectively. Associational analysis of classification and molecular characteristics revealed that C1 was associated with low pathological stage, metabolic pathways, high metabolic process, active immune process and checkpoint, sensitive drug response, as well as a low genetic mutation. Nevertheless, C2 was associated with high pathological stage, carcinogenic pathways, low metabolic process, inactive immune signatures, resistant drug response, and frequent genetic mutation. Eventually, a classifier with 60 metabolic genes was constructed, confirming the robustness of molecular classification on LUAD. Our findings promote the understanding of LUAD molecular characteristics, and the research data may be used for providing information be helpful for clinical diagnosis and treatment.

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Vascular cognitive impairment and dementia (VCID) is an age-related, mild to severe mental disability due to a broad panel of cerebrovascular disorders. Its pathobiology involves neurovascular dysfunction, blood-brain barrier disruption, white matter damage, microRNAs, oxidative stress, neuroinflammation, and gut microbiota alterations, etc. Nrf2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of redox status and controls the transcription of a panel of antioxidative and anti-inflammatory genes. By interacting with NF-κB (nuclear factor-κB), Nrf2 also fine-tunes the cellular oxidative and inflammatory balance. Aging is associated with Nrf2 dysfunction, and increasing evidence has proved the role of Nrf2 in mitigating the VCID process. Based on VCID pathobiologies and Nrf2 studies from VCID and other brain diseases, we point out several hypothetical Nrf2 targets for VCID management, including restoration of endothelial function and neurovascular coupling, preservation of blood-brain barrier integrity, reduction of amyloidopathy, promoting white matter integrity, and mitigating oxidative stress and neuroinflammation. Collectively, the Nrf2 pathway could be a promising direction for future VCID research. Targeting Nrf2 would shed light on VCID managing strategies.

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ABSTRACT Objective To explore the effects of intraoral pressure on colostrum intake. Methods Healthy women with full-term infants were admitted in the study after birth. Intraoral pressure was detected before and after the mothers' onset of lactation by a pressure sensor during a breastfeeding session. Colostrum intake was measured by weighting the infant before and after breastfeeding. The onset of lactation was confirmed by the mothers' perceptions of sudden breast fullness. Results The newborns' peak sucking pressure was 19.89±7.67kPa before the onset of lactation, dropping to 11.54±4.49kPa after mothers' onset of lactation (p<0.01). The colostrum intake was 4.02±4.26g before the onset of lactation, and 11.09±9.43g after the onset of lactation. Sucking pressure was correlated with the amount of colostrum intake before and after the onset of lactation after adjusting the confounding factors. Conclusions The newborns' intraoral pressure at early stage played a predominant role in colostrum intake. It is recommended to initiate breastfeeding immediately after the birth to take advantages of the active and robust sucking response. It is valuable to understand the importance that the sucking pressure plays in the colostrum intake and active immunity achievement during the first several days after birth.

RESUMO Objetivo Explorar o efeito das pressões intraorais na ingestão de colostro. Métodos Mulheres saudáveis com bebês a termo foram matriculadas após o nascimento. As pressões intraorais foram detectadas antes e após o início da lactação pelas mães através de um sensor de pressão durante uma sessão de amamentação. A ingestão de colostro foi mensurada pelo peso da criança antes e após a amamentação. O início da lactação foi confirmado pela percepção das mães de plenitude súbita da mama. Resultados O pico de pressão de sucção dos recém-nascidos foi de 19,89±7,67kPa antes do início da lactação e caiu para 11,54±4,49kPa após o início da lactação (p<0,01). A ingestão de colostro foi de 4,02±4,26g antes do início da lactação e 11,09±9,43g após o início da lactação. A pressão de sucção foi correlacionada com a quantidade de ingestão de colostro antes e após o início da lactação depois de terem sido feitos ajustes dos fatores de confusão. Conclusão A pressão intraoral dos recém-nascidos no estágio inicial teve um papel predominante na ingestão de colostro. Recomenda-se iniciar a amamentação imediatamente após o nascimento para aproveitar as vantagens da resposta ativa e robusta à sucção. É importante entender a importância que a pressão de sucção desempenha na ingestão de colostro e na conquista da imunidade ativa durante os primeiros dias após o nascimento.

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Professional athletes conduct high-intensitive hypoxic training often accompanied by the increase of many inflammatory-related cytokines and immunosuppression. Cucurbitacin E (CucE), as a triterpenoid isolated from Cucurbitaceae plants, exert potential anti-cancer and anti-inflammatory. However, it is unknown whether that the CucE could be used as dietary supplement for athletes to improve inflammatory response and immunosuppression. In this study, we established the simulative hypoxic training rat and monkey models and evaluated the effects of CucE on immune- and inflammation-related factors. Obvious improvement on pro-inflammatory factors and pro-lymphocyte proliferation activities were showed in CucE treated rats compared with the control. Further supplement of CucE in professional meals for cynomolgus monkeys with 4-weeks high-intensitive hypoxic training also exert effects on altitude-induced oxidative stress, inflammation and immunologic function. Furtherly, we explored the underlying mechanism of CucE in human Jurkat T cells and results showed that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-κB signaling pathway. In conclusion, CucE is expected to be a potential dietary supplement for athletes to ameliorate the inflammation and immunosuppression caused by high-intensitive exercise.

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The clean activation of methane at low temperatures remains an eminent challenge and a field of competitive research. In particular, on late transition metal surfaces such as Pt(111) or Ni(111), higher temperatures are necessary to activate the hydrocarbon molecule, but a massive deposition of carbon makes the metal surface useless for catalytic activity. However, on very low-loaded M/CeO2 (M = Pt, Ni, or Co) surfaces, the dissociation of methane occurs at room temperature, which is unexpected considering simple linear scaling relationships. This intriguing phenomenon has been studied using a combination of experimental techniques (ambient-pressure X-ray photoelectron spectroscopy, time-resolved X-ray diffraction, and X-ray absorption spectroscopy) and density functional theory-based calculations. The experimental and theoretical studies show that the size and morphology of the supported nanoparticles together with strong metal-support interactions are behind the deviations from the scaling relations. These findings point toward a possible strategy for circumventing scaling relations, producing active and stable catalysts that can be employed for methane activation and conversion.

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Research on the carbon cycle of coastal marine systems has been of wide concern recently. Accurate knowledge of the temporal and spatial distributions of sea-surface partial pressure (pCO2) can reflect the seasonal and spatial heterogeneity of CO2 flux and is, therefore, essential for quantifying the ocean's role in carbon cycling. However, it is difficult to use one model to estimate pCO2 and determine its controlling variables for an entire region due to the prominent spatiotemporal heterogeneity of pCO2 in coastal areas. Cubist is a commonly-used model for zoning; thus, it can be applied to the estimation and regional analysis of pCO2 in the Gulf of Mexico (GOM). A cubist model integrated with satellite images was used here to estimate pCO2 in the GOM, a river-dominated coastal area, using satellite products, including chlorophyll-a concentration (Chl-a), sea-surface temperature (SST) and salinity (SSS), and the diffuse attenuation coefficient at 490 nm (Kd-490). The model was based on a semi-mechanistic model and integrated the high-accuracy advantages of machine learning methods. The overall performance showed a root mean square error (RMSE) of 8.42 µatm with a coefficient of determination (R2) of 0.87. Based on the heterogeneity of environmental factors, the GOM area was divided into 6 sub-regions, consisting estuaries, near-shores, and open seas, reflecting a gradient distribution of pCO2. Factor importance and correlation analyses showed that salinity, chlorophyll-a, and temperature are the main controlling environmental variables of pCO2, corresponding to both biological and physical effects. Seasonal changes in the GOM region were also analyzed and explained by changes in the environmental variables. Therefore, considering both high accuracy and interpretability, the cubist-based model was an ideal method for pCO2 estimation and spatiotemporal heterogeneity analysis.

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For the disadvantages of both the slow reaction kinetics and the poor conductivity for Nb2O5 electrode materials as sodium-ion capacitors (SICs), Nb2O5 NRs/NMMCNF film electrode with good flexibility and high electrochemical property has been fabricated by electrospinning PAN/PMMA/H2Nb2O6·H2O homogeneous viscous suspension and followed by an annealing treatment, in which the precursor H2Nb2O6·H2O nanorods are obtained by grinding H2Nb2O6·H2O nanowires, and Nb2O5 nanorods are uniformly embedded in nitrogen doped microporous multichannel carbon nanofiber. Benefiting from the multichannel network structure, Nb2O5 NRs/NMMCNF film electrode delivers the fast kinetics of Na+-storage and the superior Na-ion storage performance, it delivers outstanding rate capability (101 mAh g-1 at 4 A g-1) and ultralong lifespan (91% capacity retention after 10,000 cycles at 2 A g-1). A Nb2O5 NRs/NMMCNF//AC SIC based on the Nb2O5 NRs@NMMCNF fiber film anode and the AC cathode is assembled. The energy density of the as-assembled device is as high as 91 Wh kg-1 and its maximum power density is 7499 W kg-1. This work offers a new structure design strategy toward intercalation-type metal oxide electrodes for application in SICs.

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In our continuing search for novel natural products with antiplasmodial activity, an extract of Aniba citrifolia was found to have good activity, with an IC50 value less than 1.25 µg/mL. After bioassay-directed fractionation, the known indolizinium alkaloid anibamine (1) and the new indolizinium alkaloid anibamine B (2) were isolated as the major bioactive constituents, with antiplasmodial IC50 values of 0.170 and 0.244 µM against the drug-resistant Dd2 strain of Plasmodium falciparum. The new coumarin anibomarin A (3), the new norneolignan anibignan A (5), and six known neolignans (7-12) were also obtained. The structures of all the isolated compounds were determined based on analyses of 1D and 2D NMR spectroscopic and mass spectrometric data, and the absolute configuration of anibignan A (5) was assigned from its ECD spectrum. Evaluation of a library of 28 anibamine analogues (13-40) indicated that quaternary charged analogues had IC50 values as low as 58 nM, while uncharged analogues were inactive or significantly less active. Assessment of the potential effects of anibamine and its analogues on the intraerythrocytic stages and morphological development of P. falciparum revealed substantial activity against ring stages for compounds with two C-10 side chains, while those with only one C-10 side chain exhibited substantial activity against trophozoite stages, suggesting different mechanisms of action.

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