Tumor metastasis is the major cause of mortality from cancer. Metabolic rewiring and the metastatic cascade are highly intertwined, co-operating to promote multiple steps of cancer metastasis. ...Metabolites generated by cancer cells influence the metastatic cascade, encompassing epithelial-mesenchymal transition (EMT), survival of cancer cells in circulation, and metastatic colonization at distant sites. A variety of molecular mechanisms underlie the prometastatic effect of tumor-derived metabolites, such as epigenetic deregulation, induction of matrix metalloproteinases (MMPs), promotion of cancer stemness, and alleviation of oxidative stress. Conversely, metastatic signaling regulates expression and activity of rate-limiting metabolic enzymes to generate prometastatic metabolites thereby reinforcing the metastasis cascade. Understanding the complex interplay between metabolism and metastasis could unravel novel molecular targets, whose intervention could lead to improvements in the treatment of cancer. In this review, we summarized the recent discoveries involving metabolism and tumor metastasis, and emphasized the promising molecular targets, with an update on the development of small molecule or biologic inhibitors against these aberrant situations in cancer.
Black carbon (BC) has emerged as an important short-lived climate forcer. Due to its light absorption properties, BC can darken the snow/ice surface, affect the energy balance, and further lead to ...acceleration of the melting of the cryosphere (e.g., glaciers, snow cover, and sea ice). By reviewing the recent published literatures, we present an overview of the historical changes, spatial distribution of BC in snow/ice, and how these changes are related to the cryospheric melting. Ice core records show a rapid increase of BC concentrations that began in the 1850s and continued throughout the 20th century, which is consistent with an increase of BC emissions owing to industrialization. A decrease of BC amount since 1970s in Arctic and European ice cores has been partially attributed to the Clean Air Act. However, in the Himalayas, BC records show a continuous increase during this period. Generally, BC concentrations in snow and ice in the mid-latitude regions are one to two orders of magnitude higher than those in the polar regions. In particular, BC concentrations in aged snow and granular ice in the ablation areas of mountain glaciers are one to three orders of magnitude higher than those in fresh snow or snowpits in the glacier accumulation areas due to BC accumulation during melting season. BC in the surface snow/ice is responsible for about 20% of the albedo reduction in the Tibetan Plateau during glacier melt season. Globally, observations and modeling results indicate that radiative forcing (RF) induced by BC in snow and ice is highest in the mid-latitudes, ranging from several W m−2 in fresh snow to hundreds of W m−2 in aged snow and granular ice in the glacier ablation areas. The large BC-in-snow RF and associated snow albedo feedback lead to an acceleration in the total glacier melt (approximately 20%) and/or a reduction in the duration of the snow cover by several days, resulting in an increase of glacier discharge. Given our limited understanding of quantifying the role of BC in cryospheric melting, it is important to synthesize the existing research on the multi-scale processes related to BC in snow and ice to identify the gaps in our understanding of these processes and to propose a path forward to improve the quality of our observations of the aforementioned phenomena to fill these gaps.
Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, ...deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in
C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs ...derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.
In this study, we examined the responses of East Asian summer monsoon (EASM) to natural (solar variability and volcanic aerosols) and anthropogenic (greenhouse gasses and aerosols) forcings simulated ...in the 17 latest Coupled Model Intercomparison Program phase 5 models with 105 realizations. The observed weakening trend of low‐level EASM circulation during 1958–2001 is partly reproduced under all‐forcing runs. A comparison of separate forcing experiments reveals that the aerosol forcing plays a primary role in driving the weakened low‐level monsoon circulation. The preferential cooling over continental East Asia caused by aerosol affects the monsoon circulation through reducing the land‐sea thermal contrast and results in higher sea level pressure over northern China. In the upper level, both natural forcing and aerosol forcing contribute to the observed southward shift of East Asian subtropical jet through changing the meridional temperature gradient.
Key Points
The observed weakening of EASM is reproduced in CMIP5 models
The aerosol weakens the monsoon by reducing the land‐sea thermal contrast
The aerosol plays a primary role in driving models' monsoon weakening
The theory of Yi-Xia and Yin-Yang is a discourse that employs the concept of Yin-Yang as metaphor for politics and interprets the relationship between Yi and Xia. Ever since the Han Dynasty, Yi-Xia ...and Yin-Yang theory emphasized the hierarchy between China and the barbarians. In the Song Dynasty, with the transformation of ideology and politics, three different new interpretations came into existence. Among them, the formation of the world structure in the Southern Song Dynasty began to affirm the coexistence relationship between China and the barbarians, which realized the reconstruction of the Yi-Xia concept.
The theory of Yi-Xia and Yin-Yang is a discourse that employs the concept of Yin-Yang as metaphor for politics and interprets the relationship between Yi and Xia. Ever since the Han Dynasty, Yi-Xia ...and Yin-Yang theory emphasized the hierarchy between China and the barbarians. In the Song Dynasty, with the transformation of ideology and politics, three different new interpretations came into existence. Among them, the formation of the world structure in the Southern Song Dynasty began to affirm the coexistence relationship between China and the barbarians, which realized the reconstruction of the Yi-Xia concept.
During cesarean section, hypotension is a frequent side effect of spinal anesthesia. As a sitting or lateral position is required for spinal anesthesia performance, which of these two positions is ...more likely to cause intraoperative nausea, vomiting, and hypotension is still unknown. This meta-analysis compared the effects of these two positions on maternal hemodynamics and intraoperative nausea and vomiting.
Systematic review and meta-analysis.
Operating room.
This study included 803 patients from 12 randomized controlled trials (RCTs).
Neuraxial anesthesia in sitting position vs. lateral position.
We chose RCTs comparing the effects of spinal anesthesia in the sitting and lateral positions on maternal hemodynamics by thoroughly searching PubMed, Embase, the Cochrane Library, and the Web of Science for articles published from database inception until October 31, 2022. The Cochrane Handbook was used to assess the methodological quality of each RCT; the results were analyzed using RevMan 5.4 software; and the Egger test was used to assess publication bias.
12 randomised controlled trials with 803 participants were ultimately included in the final analysis. No significant differences were observed between the two positions in terms of the incidence of hypotension(RR, 0.82; 95% CI, 0.58-1.16; P = 0.26; I2 = 66%), lowest systolic blood pressure(MD, -0.81; 95% CI, -7.38-5.75; P = 0.81; I2 = 86%), the dose of ephedrine(MD, -1.19; 95% CI, -4.91-2.52; P = 0.53; I2 = 83%), and number of parturients requiring ephedrine(RR, 0.97; 95% CI, 0.64-1.46; P = 0.88; I2 = 74%). For the incidence of intraoperative nausea and vomiting, there was no statistical difference between the two positions.
Parturients undergoing elective cesarean section under spinal anesthesia in the sitting or lateral position experienced similar incidence of hypotension, and there were no significant differences between these two positions in terms of the amount of ephedrine administered or the number of patients needing ephedrine. In both positions, the frequency of nausea and vomiting was comparable. The ideal position for anesthesia can be chosen based on the preferences and individual circumstances of the parturient and anesthesiologist.
Perioperative transfusion can reduce the survival rate in colorectal cancer patients. The effects of transfusion on the short- and long-term prognoses are becoming intriguing.
This systematic review ...and meta-analysis aimed to define the effects of perioperative transfusion on the short- and long-term prognoses of colorectal cancer surgery.
Thirty-six clinical observational studies, with a total of 174,036 patients, were included. Perioperative transfusion decreased overall survival (OS) (hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.24 to 0.41; P < 0.0001) and cancer-specific survival (CSS) (HR, 0.34; 95% CI, 0.21 to 0.47; P < 0.0001), but had no effect on disease-free survival (DFS) (HR, 0.17; 95% CI, - 0.12 to 0.47; P = 0.248). Transfusion could increase postoperative infectious complications (RR, 1.89, 95% CI, 1.56 to 2.28; P < 0.0001), pulmonary complications (RR, 2.01; 95% CI, 1.54 to 2.63; P < 0.0001), cardiac complications (RR, 2.20; 95% CI, 1.75 to 2.76; P < 0.0001), anastomotic complications (RR, 1.51; 95% CI, 1.29 to 1.79; P < 0.0001), reoperation(RR, 2.88; 95% CI, 2.05 to 4.05; P < 0.0001), and general complications (RR, 1.86; 95% CI, 1.66 to 2.07; P < 0.0001).
Perioperative transfusion causes a dramatically negative effect on long-term prognosis and increases short-term complications after colorectal cancer surgery.
As a conductive nanomaterial, graphene has huge potentials in nerve function restoration by promoting electrical signal transduction and metabolic activities with unique topological properties. ...Polydopamine (PDA) and arginylglycylaspartic acid (RGD) can improve cell adhesion in tissue engineering. Here we report an integrated 3D printing and layer-by-layer casting (LBLC) method in multi-layered porous scaffold fabrication. The scaffold is composed of single-layered graphene (SG) or multi-layered graphene (MG) and polycaprolactone (PCL). The electrically conductive 3D graphene scaffold can significantly improve neural expression both in vitro and in vivo. It promotes successful axonal regrowth and remyelination after peripheral nerve injury. These findings implicate that graphene-based nanotechnology have great potentials in peripheral nerve restoration in preclinical and clinical application.
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