Integrated multi-omics analysis and machine learning developed a prognostic model based on mitochondrial function in a large multicenter cohort for Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death. METHODS: We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose. RESULTS: MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis. CONCLUSION: The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.

Association between the triglyceride-glucose index and cognitive impairment in China: a community population-based cross-sectional study.

INTRODUCTION: Insulin resistance (IR) is a feature of metabolic syndrome and plays an important role in cognitive impairment (CI). The triglyceride-glucose (TyG) index is a convenient and cost-effective surrogate for assessing IR. This study aimed to assess the association between the TyG index and CI. METHODS: This community population-based cross-sectional study used a cluster-sampling methodology. All participants underwent the education-based Mini-Mental State Examination (MMSE), and those with CI were identified using standard thresholds. The fasting blood triglyceride and glucose levels were measured in the morning, and the TyG index was calculated as ln (½ fasting triglyceride level [mg/dL] × fasting blood glucose level [mg/dL]). Multivariable logistic regression and subgroup analysis were used to assess the relationship between the TyG index and CI. RESULTS: This study included 1484 subjects, of which 93 (6.27%) met the CI criteria. Multivariable logistic regression showed that CI incidence increased by 64% per unit increase in the TyG index (odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.02-2.63, p = 0.042). CI risk was 2.64-fold higher in the highest TyG index quartile compared to the lowest TyG index quartile (OR = 2.64, 95% CI: 1.19-5.85, p = 0.016). Finally, interaction analysis showed that sex, age, hypertension, and diabetes did not significantly affect the association between the TyG index and CI. CONCLUSION: The present study suggested that an elevated TyG index was associated with a higher CI risk. Subjects with a higher TyG index should manage and treat at an early stage to alleviate the cognitive decline.

Restorative benefits of urban green space: Physiological, psychological restoration and eye movement analysis.

Urban life is associated with a range of health risks. However, urban green spaces have been found to promote health recovery and reduce mental stress. This study sought to assess the influence of the spatial and environmental characteristics of urban green space on environmental restoration. We measured physiological and psychological changes among 60 participants to evaluate the restorative benefits of 12 green spaces in Shenyang. The Perceived Restorativeness Scale and two physiological measures (heart rate variation and skin conductance response) were used to analyze the effects of spatial characteristics on restorative benefits. In addition, eye-tracking was used to explore the influence of environmental components on restorative benefits. The results revealed that, although there were slight differences between physiological and psychological findings, both confirmed that urban green space had a restorative benefit. Partially-open green spaces with a high degree of naturalness had more positive effects than open green spaces with a high degree of hard paved spaces. Eye movement analysis results revealed that trees and shrubs, as well as water, had a positive effect on the environmental restoration benefits, whereas buildings and paving had a negative effect. Among environmental features, trees and shrubs, water, and buildings exerted the strongest effects on environment restoration. In the future, combining spatial characteristics and environmental components will aid improvement of the restorative qualities of urban green space.

Kinetics of Photoelectrochemical Oxidation of Methanol on Hematite Photoanodes.

The kinetics of photoelectrochemical (PEC) oxidation of methanol, as a model organic substrate, on α-Fe2O3 photoanodes are studied using photoinduced absorption spectroscopy and transient photocurrent measurements. Methanol is oxidized on α-Fe2O3 to formaldehyde with near unity Faradaic efficiency. A rate law analysis under quasi-steady-state conditions of PEC methanol oxidation indicates that rate of reaction is second order in the density of surface holes on hematite and independent of the applied potential. Analogous data on anatase TiO2 photoanodes indicate similar second-order kinetics for methanol oxidation with a second-order rate constant 2 orders of magnitude higher than that on α-Fe2O3. Kinetic isotope effect studies determine that the rate constant for methanol oxidation on α-Fe2O3 is retarded ∼20-fold by H/D substitution. Employing these data, we propose a mechanism for methanol oxidation under 1 sun irradiation on these metal oxide surfaces and discuss the implications for the efficient PEC methanol oxidation to formaldehyde and concomitant hydrogen evolution.

Enhanced Sb(V) removal of sulfate-rich wastewater by anaerobic granular sludge assisted with Fe/C amendment.

Antimony (Sb) and sulfate are two common pollutants in Sb mine drainage and Sb-containing textile wastewater. In this paper, it was found that iron­carbon (Fe/C) enhanced Sb(V) removal from sulfate-rich wastewater by anaerobic granular sludge (AnGS). Sulfate inhibited Sb(V) removal (S + Sb, k = 0.101), while Fe/C alleviated the inhibition and increased Sb(V) removal rate by 2.3 times (Fe/C + S + Sb, k = 0.236). Fe/C could promote the removal of Sb(III), and Sb(III) content decreased significantly after 8 h. Meanwhile, Fe/C enhanced the removal of sulfate. The 3D-EEM spectrum of supernatant in Fe/C + S + Sb group (at 24 h) showed that Fe/C stimulated the production of soluble microbial products (SMP) in wastewater. SMP alleviated the inhibition of sulfate, promoting AnGS to reduce Sb(V). Sb(V) could be reduced to Sb(III) both by AnGS and sulfides produced from sulfate reduction. Further analysis of extracellular polymeric substances (EPS) and AnGS showed that Fe/C increased the adsorbed Sb(V) in EPS and the c-type cytochrome content in AnGS, which may be beneficial for Sb(V) removal. Sb(V) reduction in Fe/C + S + Sb group may be related to the genus Acinetobacter, while in Sb group, several bacteria may be involved in Sb(V) reduction, such as Acinetobacter, Pseudomonas and Corynebacterium. This study provided insights into Fe/C-enhanced Sb(V) removal from sulfate-rich wastewater.

TRIM40 interacts with ROCK1 directly and inhibits colorectal cancer cell proliferation through the c-Myc/p21 axis.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the digestive tract, and to date, morbidity and mortality rates remain high. While existing therapeutic methods have achieved certain effective outcomes, there are still many problems in treating this disease. Therefore, it is still urgent to constantly find new therapeutic targets in CRC that could lead to new therapeutics. METHODS: Immunohistochemistry, Real-time PCR and Western Blot were employed to measure mRNA and protein levels of the target protein, respectively. The proliferation ability of CRC cells was evaluated using ATP assay, Soft agar assay, and nude mouse subcutaneous tumorigenesis assay. Protein Degradation Assay was conducted to determine protein degradation rate, while Ubiquitination assay was used to assess the ubiquitination modification level of target proteins. Immunoprecipitation assay was used to study protein interactions, and pull-down assay was employed to investigate direct interactions between proteins. RESULTS: TRIM40 was significantly down-regulated in CRC tissues, with its expression levels positively correlating with disease prognosis. Using both in vitro and in vivo approaches, it was demonstrated that TRIM40 could significantly inhibit the proliferation of CRC cells. Molecular mechanism studies showed that TRIM40 directly binds to and ubiquitinates ROCK1 protein, accelerating its degradation and subsequently reducing the stability of c-Myc protein. This cascade of events results in the release of transcriptional inhibition of p21 by c-Myc, leading to increased p21 expression and G0/G1 phase arrest in CRC cells. CONCLUSION: This research suggests that TRIM40 could be a valuable therapeutic target for the treatment of CRC.

Photoinduced Absorption Spectroscopy of Photoelectrocatalytic Methylene Blue Oxidation on Titania and Hematite: The Thermodynamic and Kinetic Impacts on Reaction Pathways.

Photoelectrochemical oxidation of methylene blue is investigated, with particular focus on the difference in kinetics and thermodynamics of decoloration and mineralization employing photoinduced absorption spectroscopy. Hematite and titania photoanodes are used for the comparison of both reactions, which is determined to be associated with the depth of the valence band (3.2 vs 2.5 V for titania and hematite, respectively). Methylene blue is mineralized by the titania photoanode, however it is only oxidized to small fragments by hematite. Such difference is related to the valence band potential that provides the thermodynamic driving force for photogenerated holes in both materials. In addition, the kinetic competition of water oxidation is found to occur on titania by controlling the pH of the electrolyte. In the pH 14 electrolyte, mineralization of methylene blue is suppressed due to the faster and dominant kinetics of water oxidation, in contrast to the complete mineralization in the near neutral electrolyte where water oxidation kinetics are modest. These results clearly address the importance considering both thermodynamic and kinetic challenges of methylene blue oxidation, which has been thought to be an easy molecule to oxidize, as the model reaction in the application of photo(electro)catalysis using metal oxides.

CRTAC1 enhances the chemosensitivity of non-small cell lung cancer to cisplatin by eliciting RyR-mediated calcium release and inhibiting Akt1 expression.

Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in patients with non-small cell lung cancer (NSCLC). Here, our results obtained from analyses of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca2+ levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation and, in turn, enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca2+-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.

Mechanistic Insights into Selective Acetaldehyde Formation from Ethanol Oxidation on Hematite Photoanodes by Operando Spectroelectrochemistry.

This study employed operando spectroelectrochemical l and photoelectrochemical methods to investigate the charge carrier dynamics of photogenerated holes in hematite for ethanol oxidation and its possible over-oxidation. Ethanol oxidation was found to form acetaldehyde with around 100 % initial selectivity and faradaic efficiency. The overoxidation of acetaldehyde was suppressed by being unable to kinetically compete with ethanol oxidation in terms of turnover frequency by a factor of ten. Temperature-dependent rate law analyses were applied to determine the activation energies of these two oxidations. For the ethanol oxidation, the activation energy was 195 meV, compared to 398 meV for acetaldehyde oxidation. These results were correlated with the valence band potential to elucidate the advantage of using hematite for safer and sustainable value-added aldehyde synthesis compared to the industrial method. The dynamics of ethanol oxidation also addressed the challenges in broad-spectrum deep oxidation of organic compounds in water purification using metal oxides.

Morphology-Controlled Synthesis of Polyphosphazene-Based Micro- and Nano-Materials and Their Application as Flame Retardants.

Common flame retardants, such as halogen-based materials, are being phased-out owing to their harmful environmental and health effects. We prepared poly-(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) (PZS) microspheres, nanotubes, capsicum-like nanotubes, and branched nanotubes as flame retardants. An increase in reaction temperature changed the morphology from nanotubes to microspheres. A PZS shape had a positive effect on the flame retardancy of polyethylene terephthalate (PET). The PZS with a capsicum-like nanotube morphology had the best flame retardancy, and the PET limiting oxygen index increased from 25.2% to 34.4%. The flame retardancy capability was followed by PZS microspheres (33.1%), branched nanotubes (32.8%), and nanotubes (32.5%). The capsicum-like nanotubes promote the formation of highly dense and continuous carbon layers, and they release a non-combustible gas (CO2). This study confirms polyphosphazene-based flame retardants as viable and environmentally-friendly alternatives to common flame retardants. It also presents a novel and facile design and synthesis of morphology-controlled nanomaterials with enhanced flame retardant properties.

Multihole water oxidation catalysis on haematite photoanodes revealed by operando spectroelectrochemistry and DFT.

Water oxidation is the key kinetic bottleneck of photoelectrochemical devices for fuel synthesis. Despite advances in the identification of intermediates, elucidating the catalytic mechanism of this multi-redox reaction on metal-oxide photoanodes remains a significant experimental and theoretical challenge. Here, we report an experimental analysis of water oxidation kinetics on four widely studied metal oxides, focusing particularly on haematite. We observe that haematite is able to access a reaction mechanism that is third order in surface-hole density, which is assigned to equilibration between three surface holes and M(OH)-O-M(OH) sites. This reaction exhibits low activation energy (Ea ≈ 60 meV). Density functional theory is used to determine the energetics of charge accumulation and O-O bond formation on a model haematite (110) surface. The proposed mechanism shows parallels with the function of the oxygen evolving complex of photosystem II, and provides new insights into the mechanism of heterogeneous water oxidation on a metal oxide surface.

The Inhibitory Effect of α/ß-Hydrolase Domain-Containing 6 (ABHD6) on the Surface Targeting of GluA2- and GluA3-Containing AMPA Receptors.

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control the biosynthesis, membrane trafficking, and synaptic targeting of AMPARs. Our previous report showed that α/ß-hydrolase domain-containing 6 (ABHD6), an auxiliary subunit for AMPARs, suppresses the membrane delivery and function of GluA1-containing receptors in both heterologous cells and neurons. However, it remained unclear whether ABHD6 affects the membrane trafficking of glutamate receptor subunits, GluA2 and GluA3. Here, we examine the effects of ABHD6 overexpression in HEK293T cells expressing GluA1, GluA2, GluA3, and stargazin, either alone or in combination. The results show that ABHD6 suppresses the glutamate-induced currents and the membrane expression of AMPARs when expressing GluA2 or GluA3 in the HEK293T cells. We generated a series of GluA2 and GluA3 C-terminal deletion constructs and confirm that the C-terminus of GluAs is required for ABHD6's inhibitory effects on glutamate-induced currents and surface expression of GluAs. Meanwhile, our pull-down experiments reveal that ABHD6 binds to GluA1-3, and deletion of the C-terminal domain of GluAs abolishes this binding. These findings demonstrate that ABHD6 inhibits the AMPAR-mediated currents and its surface expression, independent of the type of AMPAR subunits, and this inhibitor's effects are mediated through the binding with the GluAs C-terminal regions.

Efficient suppression of back electron/hole recombination in cobalt phosphate surface-modified undoped bismuth vanadate photoanodes.

In this paper, we compared for the first time the dynamics of photogenerated holes in BiVO4 photoanodes with and without CoPi surface modification, employing transient absorption and photocurrent measurements on microsecond to second timescales. CoPi surface modification is known to cathodically shift the water oxidation onset potential; however, the reason for this improvement has not until now been fully understood. The transient absorption and photocurrent data were analyzed using a simple kinetic model, which allows quantification of the competition between electron/hole recombination and water oxidation. The results of this model are shown to be in excellent agreement with the measured photocurrent data. We demonstrate that the origin of the improvement of photocurrent onset resulting from CoPi treatment is primarily due to retardation of back electron/hole recombination across the space charge layer; no evidence of catalytic water oxidation via CoPi was observed.