Initiation of adaptive feeding within 24 h after burn injury improves nutritional therapy for severely burned patients.

Introduction and objective: Nutritional therapy is a crucial component of treatment for severely burned patients. Although overly aggressive enteral nutrition immediately after burn injury has potential risks, nutritional disruption after a severe burn can also increase infection risk and delay wound healing. For approximately six decades, the Ruijin Hospital Burn Center has used two distinct approaches for patients during the early period after burn injury: complete fasting or adaptive feeding. Notably, adaptive feeding more closely resembles enteral nutrition. In this retrospective study, we analyzed factors influencing the selection of either modality, as well as the benefits of adaptive feeding. We sought to promote adaptive feeding as a precursor to initiating enteral nutrition. Patients and methods: This retrospective study analyzed medical data from adult patients with extensive burns between January 2009 and December 2020. All patients had been admitted to the burn department within 24 h after injury and had a burned area comprising >30% of total body surface area. Patients were divided into two groups: adaptive feeding and fasting. We examined the total burned area, full-thickness burned area, burn type, inhalation injury, start time of adaptive feeding, and start time of enteral nutrition. Outcome measures were 28-day mortality and hospital mortality. Results: Univariate analysis revealed significant differences in burn type, percent of total body surface area (TBSA), full-thickness burned area, and inhalation injury between the adaptive feeding and fasting groups (all p < 0.05). Linear regression analysis showed that full-thickness burned area and inhalation injury were the main factors influencing the start time of adaptive feeding in patients with severe burns (p < 0.05). After propensity score matching analysis, the results showed that the start time of enteral nutrition was significantly earlier in the adaptive feeding group (p < 0.01). However, overall mortality, 28-day mortality, and length of hospital stay did not significantly improve in the adaptive feeding group. The incidence of intolerance after enteral nutrition therapy did not significantly differ between groups. Conclusion: The results of the study showed that larger full-thickness burned areas and concomitant inhalation injury were the primary factors considered by physicians when selecting complete fasting for severely burned patients. Moreover, the results indicate that adaptive feeding improves nutritional therapy for severely burned patients by shortening the time between injury and initiation of enteral nutrition. Complete fasting due to concerns about extensive burned area and inhalation injuries does not reduce the incidence of enteral nutrition intolerance; instead, it delays the initiation of enteral nutrition.

Increase in GPIHBP1 expression in advanced stage colorectal cancer indicates poor immune surveillance.

Background: Glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a crucial role in fatty acid metabolism, which is involved in the progression of colorectal cancer (CRC). The aim of this study was to determine the expressional variations of GPIHBP1 in CRC at different stages and to verify whether this protein affects the shaping of the immune microenvironment of cancer cells. Methods: Variations of GPIHBP1 messenger RNA (mRNA) levels were first analysed using The Cancer Genome Atlas (TCGA) database. Protein levels of GPIHBP1 in cancer nest cells, stromal cells or surrounding normal tissues from 68 patients with CRC were checked by immunohistochemistry. Infiltration of immune cells such as macrophages, myeloid-derived suppressor cells (MDSCs), CD8+ and CD56+ cells was parallelly stained in the same tissues. Ectopic GPIHBP1 expressed colonic tumour cells were transplanted into the back of mice. Tumour growth and immune cell infiltrations were also observed. Results: Compared with those in healthy tissues, GPIHBP1 mRNA and protein levels decreased in the patients with CRC at Dukes A-B stage but gradually increased in the patients at Dukes C-D stage. GPIHBP1 in foci or stroma was positively correlated with recruited macrophages or MDSCs and negatively correlated with recruited CD8+, CD56+ or granzyme+ cells. The mice injected with GPIHBP1 overexpression cells bore large tumours. Histological analysis confirmed the infiltration of many macrophages and MDSCs but less CD8+ T or CD56+ cells. Conclusions: The increased expression of GPIHBP1 is involved in the progression of CRC. High GPIHBP1 level of advanced CRC indicates efficient immune evasion in tumour microenvironment.

Development and validation of dietary depression index in Chinese adults.

Objective: Previous studies have suggested diet was associated with depressive symptoms. We aimed to develop and validate Dietary Depression Index (DDI) based on dietary prediction of depression in a large Chinese cancer screening cohort.Methods: In the training set (n = 2729), we developed DDI by using intake of 20 food groups derived from a food frequency questionnaire to predict depression as assessed by Patient Health Questionnaire-9 based on the reduced rank regression method. Sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the performance of DDI in evaluating depression in the validation dataset (n = 1176).Results: Receiver operating characteristic analysis was constructed to determine the best cut-off value of DDI in predicting depression. In the study population, the DDI ranged from -3.126 to 1.810. The discriminative ability of DDI in predicting depression was good with the AUC of 0.799 overall, 0.794 in males and 0.808 in females. The best cut-off values of DDI for depression prediction were 0.204 overall, 0.330 in males and 0.034 in females. DDI was a validated method to assess the effects of diet on depression.Conclusion: Among individual food components in DDI, fermented vegetables, fresh vegetables, whole grains and onions were inversely associated, whereas legumes, pickled vegetables and rice were positively associated with depressive symptoms.

Comparison of toxic effects and underlying mechanisms of carbon quantum dots and CdSe quantum dots on Chromochloris zofingiensis from the chemical composition perspective.

Quantum dots (QDs) are widely utilized semiconductor nanocrystal materials with both nanotoxicity and composition-related toxicity. To determine the toxicological impacts and underlying mechanisms of QDs with different compositions on microalgae, carbon QDs (CQDs) and CdSe QDs were used in the present study. Results showed that QDs composed of CdSe were more toxic than QDs composed of carbon, which inhibited cell growth, with reductions in chl b content, chlorophyll fluorescence parameters, and increases in lipids and starch (two major storage substances). In addition, CdSe QDs elevated reactive oxygen species (ROS), resulting in oxidative damage, while CQDs had little effect on antioxidants. Comparative transcriptome analysis showed that gene expression was accelerated by CdSe QDs, and there was a compensatory upregulation of porphyrin metabolism, potentially to support chlorophyll synthesis. In addition, an MYB transcription factor was predicted by weighted gene co-expression network analysis (WGCNA) to serve as regulator in nanoparticle toxicity, while glutathione peroxidase (GPX) and dual-specificity tyrosine phosphorylation regulated kinases 2/3/4 (DYRK2/3/4) may be key mediators of the composition-related toxicity of CdSe QDs. This study highlights the critical role of QDs' composition in determining their impacts on aquatic microalgae, providing a theoretical reference for selecting appropriate QDs materials for various industrial applications.

Nitrogen-Mediated Promotion of Cobalt-Based Oxygen Evolution Catalyst for Practical Anion-Exchange Membrane Electrolysis.

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. Results: The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). Conclusions: A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Translational Relevance: Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.

Protective effects of patchouli alcohol against DSS-induced ulcerative colitis.

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.

Molecular differentiation between complete and incomplete responders to neoadjuvant therapy in rectal cancer.

Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer, but only 20-40% of patients completely respond to this treatment. Methods: To define the molecular features that are associated with response to nCRT, we generated and collected genomic and transcriptomic data from 712 cancers prior to treatment from our own data and from publicly available data. Results: We found that patients with a complete response have decreased risk of both local recurrence and future metastasis. We identified multiple differences in DNA mutations and transcripts between complete and incomplete responders. Complete responder tumors have a higher tumor mutation burden and more significant co-occurring mutations than the incomplete responder tumors. In addition, mutations in DNA repair genes (across multiple mechanisms of repair) were enriched in complete responders and they also had lower expression of these genes indicating that defective DNA repair is associated with complete response to nCRT. Using logistic regression, we identified three significant predictors of complete response: tumor size, mutations within specific network genes, and the existence of three or more specific co-occurrent mutations. In incompletely responder tumors, abnormal cell-cell interaction and increased cancer associated fibroblasts were associated with recurrence. Additionally, gene expression analysis identified a subset of immune hot tumors with worse outcomes and upregulated of immune checkpoint proteins. Conclusions: Overall, our study provides a comprehensive understanding of the molecular features associated with response to nCRT and the molecular differences in non-responder tumors that later reoccur. This knowledge may provide critical insight for the development of precision therapy for rectal cancer.

SENP3 sensitizes macrophages to ferroptosis via de-SUMOylation of FSP1.

Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.

Scalable Fabrication of Large-Scale, 3D, and Stretchable Circuits.

Stretchable electronics have demonstrated excellent potential in wearable healthcare and conformal integration. Achieving the scalable fabrication of stretchable devices with high functional density is the cornerstone to enable the practical applications of stretchable electronics. Here, a comprehensive methodology for realizing large-scale, 3D, and stretchable circuits (3D-LSC) is reported. The soft copper-clad laminate (S-CCL) based on the "cast and cure" process facilitates patterning the planar interconnects with the scale beyond 1 m. With the ability to form through, buried and blind VIAs in the multilayer stack of S-CCLs, high functional density can be achieved by further creating vertical interconnects in stacked S-CCLs. The application of temporary bonding substrate effectively minimizes the misalignments caused by residual strain and thermal strain. 3D-LSC enables the batch production of stretchable skin patches based on five-layer stretchable circuits, which can serve as a miniaturized system for physiological signals monitoring with wireless power delivery. The fabrications of conformal antenna and stretchable light-emitting diode display further illustrate the potential of 3D-LSC in realizing large-scale stretchable devices.

Association between dietary riboflavin intake and cognitive decline in older adults: a cross-sectional analysis.

BACKGROUND: Research exploring the link between dietary riboflavin intake and cognitive decline in this demographic is limited. Our aim was to examine the association between riboflavin intake levels and cognitive decline. METHODS: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. The Consortium to Establish a Registry for Alzheimer's Disease test Word Learning delayed recall trial (DR), Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and Z test were used to evaluate cognitive performance. Multivariate logistic regression, restricted cubic spline and subgroup analysis were performed to evaluate the associations between riboflavin intake and cognitive decline. RESULTS: The study included a total of 2255 patients, with 47.9% being male. The incidence of cognitive decline was 23.8%. After adjusting for all selected covariates, we found that high riboflavin intake was associated with a lower risk of cognitive impairment in adults in the United States. When riboflavin intake was used as a Categorical variable, compared to those with the lowest intake, the odds ratio (OR) of individuals with the highest riboflavin intake for DR test, AFT test, DSST test and Z test were 0.73 (95% CI: 0.53~1), 0.68(95% CI: 0.49-0.96),0.53(95% CI: 0.37-0.77) and 0.56(95% CI: 0.39-0.8). The study also found an L-shaped association between riboflavin intake and cognitive decline, with an inflection point at approximately 2.984 mg/d. CONCLUSIONS: Our cross-sectional study in a nationwide sample of American old adults suggests that dietary riboflavin intake was negative associated with cognitive decline.

Association between serum chloride and in-hospital mortality in congestive heart failure with diabetes: Data from the MIMIC-IV database.

Background: Congestive heart failure (CHF) demonstrates a heightened prevalence in individuals with diabetes mellitus within Intensive Care Units. The occurrence of abnormal chloride levels is frequently observed in critically ill patients, yet its clinical significance remains subject to debate. This study endeavors to explore the relationship between serum chloride levels and in-hospital mortality among patients affected by both congestive heart failure and diabetes. Methods: A retrospective cohort study was conducted, utilizing data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, focusing on adult patients in the United States. The impact of serum chloride levels upon ICU admission on in-hospital mortality was analyzed using multivariable logistic regression models, generalized additive models and subgroup analysis. Results: The study encompassed 7,063 patients with coexisting diabetes and congestive heart failure. The fully adjusted model revealed an inverse association between serum chloride levels and in-hospital mortality. As a tertile variable (Q3 vs Q1), the odds ratio (OR) was 0.73 with a 95% confidence interval (CI) of 0.54-0.98 (p = 0.039). As a continuous variable, per 1 mmol/L increment, the OR (95% CI) was 0.97 (0.96-0.99, p = 0.01). The relationship between serum chloride and in-hospital mortality demonstrated linearity (non-linear p = 0.958). Stratified analyses further validated the robustness of this correlation. Conclusions: Serum chloride levels exhibited a negative association with in-hospital mortality in patients with both congestive heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are warranted to corroborate and validate the findings presented in this investigation.

U-shaped association between serum calcium and in-hospital mortality in diabetes patients with congestive heart failure: a cohort study.

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.

Facet-switching of rate-determining step on copper in CO2-to-ethylene electroreduction.

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

Single-Cell RNA Sequencing Identifies WARS1+ Mesenchymal Stem Cells with Enhanced Immunomodulatory Capacity and Improved Therapeutic Efficacy.

Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.

Biochar promotes microbial CO2 fixation by regulating feedback inhibition of metabolites.

Chemoautotrophs, the crucial contributors to biological carbon fixation, derive energy from reducing specific inorganic substances and utilize CO2 for growth. However, the release of extracellular free organic carbon (EFOC) by chemoautotrophic microorganisms can inhibit their own growth and metabolism. To reduce the feedback inhibition effect, a low-release biochar (BC-LR) was applied to adsorb EFOC. BC-LR not only adsorbed EFOC, but also selectively adsorbed the main inhibitory component, low molecular weight organics, in EFOC. In contrast, ordinary biochar could not effectively adsorb EFOC and its addition inhibited microbial growth and CO2 fixation. In Transwell culture, BC-LR promoted microbial growth by 190% and CO2 fixation by 29%, and exhibited better economic advantage, when compared with granular activated carbon. These findings provide a novel insight into the interaction between biochar and autotrophic microbial metabolism, offering an economically feasible approach to mitigate feedback inhibition of metabolites and promoting biological CO2 fixation.

Bioinspired Nano-Photosensitizer-Activated Caspase-3/GSDME Pathway Induces Pyroptosis in Lung Cancer Cells.

Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase-3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase-3 plays a vital role in pyroptosis-based cancer therapy. Herein, a human cell membrane vesicle-based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G-protein (VSVG) to anchor nano-photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase-3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light-activated PDT.

Effects of the Interaction between Rumen Microbiota Density-VFAs-Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau.

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.

A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multi-Parametric MRI.

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression. EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index and Multiparametric MRI (MTP) for quantitative brain mapping. Tumor and peri-tumor tissues were analyzed for AQP4 expression via immunofluorescence. Correlations between imaging parameters, glymphatic function (DTI-ALPS index), and AQP4 expression were statistically assessed. RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), brain tumor patients exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; p = 0.001) and increased cerebrospinal fluid (CSF) volume (201.376 cm³ vs. 115.957 cm³; p = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, p < 0.001), while AQP4 expression correlated positively with peritumoral brain edema (PTBE) volume (r: 0.989; p < 0.001) and negatively with PD in PTBE areas (ρ: -0.506; p < 0.001). CONCLUSIONS: Our findings highlight the interplay between tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, showing the utility of DTI-ALPS and MTP in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system.

LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1-166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.