Recurrence and Complications of Peri-operative Steroid Injection of Keloids: A Systematic Review and Meta-analysis.

Keloid scars are a particularly challenging fibroproliferative wound healing disorder with a variety of proposed management approaches including concurrent surgery and intralesional steroid injection. We aimed to identify the optimum time for triamcinolone injection of keloids, by comparing the recurrence and complication occurrence in patients who received pre-, intra- or post-operative injection. Studies reporting on the rate of recurrence and complication occurrence following treatment of keloid scarring with concurrent surgical excision and intralesional steroid injection were identified from the PubMed, Web of science and Embase databases. The I-squared (I2) statistic was used to quantify the variability in study estimates due to heterogeneity and to determine whether the fixed or random effect models will be employed. Publication bias was visualized through funnel plots and tested with the Egger's test. We found that the recurrence rate was significantly lower with post-operative injection compared to intra-operative injection (p < 0.001) and pre-operative injection (p = 0.009). A significant difference between intra-operative and pre-operative injection was not found (p = 0.46). In conclusion, post-operative steroid injection after surgical excision results in lower keloid recurrence compared to pre- and intra-operative injection.Level of Evidence IV "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

Enhancing bighead carp cutting: Chilled storage insights and machine vision-based segmentation algorithm development.

To enhance market demand and fish utilization, cutting processing is essential for fish. Bighead carp were cut into four primary cuts: head, dorsal, belly, and tail, collectively accounting for 77.03% of the fish's total weight. These cuts were refrigerated at 4 °C for 10 days, during which the muscle from each cut was analyzed. Pseudomonas.fragi proliferated most rapidly and was most abundant in eye muscle (EM), while Aeromonas.sobria showed similar growth patterns in tail muscle (TM). Notably, EM exhibited the highest rate of fat oxidation. TM experienced the most rapid protein degradation. Furthermore, to facilitate the cutting applied in mechanical processing, a machine vision-based algorithm was developed. This algorithm utilized color threshold and morphological parameters to segment image background and divide bighead carp region. Consequently, each cut of bighead carp had a different storage quality and the machine vision-based algorithm proved effective for processing bighead carp.

Functional Analysis of ß-Carotene Oxygenase 2 (BCO2) Gene in Yesso Scallop (Patinopecten yessoensis).

Carotenoids are essential nutrients for humans and animals, and carotenoid coloration represents an important meat quality parameter for many farmed animals. Increasingly, studies have demonstrated that vertebrate carotenoid cleavage oxygenases (CCOs) are essential enzymes in carotenoid metabolism and are therefore potential candidate genes for improving carotenoid deposition. However, our understanding of carotenoid bioavailability and CCOs functions in invertebrates, particularly marine species, is currently quite limited. We previously identified that a CCO homolog, PyBCO-like 1, was the causal gene for carotenoid coloration in the 'Haida golden scallop', a variety of Yesso scallop (Patinopecten yessoensis) characterized by carotenoid enrichment. Here, we found that another CCO-encoding gene named PyBCO2 (ß-carotene oxygenase 2) was widely expressed in P. yessoensis organs/tissues, with the highest expression in striated muscle. Inhibiting BCO2 expression in P. yessoensis through RNA interference led to increased carotenoid (pectenolone and pectenoxanthin) deposition in the striated muscle, and the color of the striated muscle changed from white to light orange. Our results indicate that PyBCO2 might be a candidate gene used for improving carotenoid content in normal Yesso scallops, and also in 'Haida golden scallops'.

A large presence/absence variation in the promotor of the ClLOG gene determines trichome elongation in watermelon.

KEY MESSAGE: The ClLOG gene encoding a cytokinin riboside 5'-monophosphate phosphoribohydrolase determines trichome length in watermelon, which is associated with its promoter variations. Trichomes, which are differentiated from epidermal cells, are special accessory structures that cover the above-ground organs of plants and possibly contribute to biotic and abiotic stress resistance. Here, a bulked segregant analysis (BSA) of an F2 population with significant variations in trichome length was undertaken. A 1.84-Mb candidate region on chromosome 10 was associated with trichome length. Resequencing and fine-mapping analyses indicated that a 12-kb structural variation in the promoter of Cla97C10G203450 (ClLOG) led to a significant expression difference in this gene in watermelon lines with different trichome lengths. In addition, a virus-induced gene silencing analysis confirmed that ClLOG positively regulated trichome elongation. These findings provide new information and identify a potential target gene for controlling multicellular trichome elongation in watermelon.

Aggregation and proliferation of B cells and T cells in MALTs upon Cryptocaryon irritans infection in large yellow croaker Larimichthys crocea.

Mucosal immunity in mucosa-associated lymphoid tissues (MALTs) plays crucial roles in resisting infection by pathogens, including parasites, bacteria and viruses. However, the mucosal immune response in the MALTs of large yellow croaker (Larimichthys crocea) upon parasitic infection remains largely unknown. In this study, we investigated the role of B cells and T cells in the MALTs of large yellow croaker following Cryptocaryon irritans infection. Upon C. irritans infection, the total IgM and IgT antibody levels were significantly increased in the skin mucus and gill mucus. Notably, parasite-specific IgM antibody level was increased in the serum, skin and gill mucus following parasitic infection, while the level of parasite-specific IgT antibody was exclusively increased in MALTs. Moreover, parasitic infection induced both local and systemic aggregation and proliferation of IgM+ B cells, suggesting that the increased levels of IgM in mucus may be derived from both systemic and mucosal immune tissues. In addition, we observed significant aggregation and proliferation of T cells in the gill, head kidney and spleen, suggesting that T cells may also be involved in the systemic and mucosal immune responses upon parasitic infection. Overall, our findings provided further insights into the role of immunoglobulins against pathogenic infection, and the simultaneous aggregation and proliferation of both B cells and T cells at mucosal surfaces suggested potential interactions between these two major lymphocyte populations during parasitic infection.

Flavonoids with Anti-Angiogenesis Function in Cancer.

The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/ß-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.

High Expression Level of TRIP6 is Correlated with Poor Prognosis in Colorectal Cancer and Promotes Tumor Cell Proliferation and Migration.

Globally, colorectal cancer (CRC) is one of the leading causes of health problems. More reliable molecular biomarkers for early diagnosis in CRC patients are needed. A crucial role for thyroid hormone receptor interacting protein 6 (TRIP6) is played in tumorigenesis and tumor growth. Our study aims to determine the diagnostic and prognostic roles of TRIP6 at CRC. TRIP6 gene expression levels were analyzed in this study from public databases. The relationship between TRIP6 expression and clinicopathological characteristics was explored by logistic regression analysis. Based on Kaplan-Meier (K-M) survival curves and receiver operating characteristic curves (ROC) analysis, the prognostic and diagnostic values of TRIP6 were determined. Protein-protein interaction (PPI) networks analysis were performed using the STRING database. A Spearman's correlation analysis applied for examining the correlation between TRIP6 expression, immune cell infiltration, and immune checkpoint genes. Moreover, colony formation assay and transwell assay were used to investigate the functions of TRIP6. TRIP6 was highly expressed in CRC cancer tissues and cells. K-M survival analysis indicated that a high expression of TRIP6 was associated with poor prognosis. TRIP6 expression was obviously associated with immune cell infiltration and immune checkpoint gene expression. For validation, the results of collected clinical CRC samples show that TRIP6 levels in CRC tumor tissue were higher than those of paired adjacent colorectal tissues. Additionally, in vitro experiments suggested that TRIP6 knockdown suppressed proliferation and migration in CRC cell line RKO. TRIP6 overexpression promoted the proliferation and migration of normal colon cell line NCM460. High TRIP6 expression is associated with poor prognosis in colorectal cancer and promotes tumor cell proliferation and migration which may be a potential diagnostic and prognostic biomarker and a promising therapeutic target for CRC, providing new insights into its role in CRC.

Coupling Curvature and Hydrophobicity: A Counterintuitive Strategy for Efficient Electroreduction of Nitrate into Ammonia.

The electrochemical upcycling of nitrate (NO3-) to ammonia (NH3) holds promise for synergizing both wastewater treatment and NH3 synthesis. Efficient stripping of gaseous products (NH3, H2, and N2) from electrocatalysts is crucial for continuous and stable electrochemical reactions. This study evaluated a layered electrocatalyst structure using copper (Cu) dendrites to enable a high curvature and hydrophobicity and achieve a stratified liquid contact at the gas-liquid interface of the electrocatalyst layer. As such, gaseous product desorption or displacement from electrocatalysts was enhanced due to the separation of a wetted reaction zone and a nonwetted zone for gas transfer. Consequently, this electrocatalyst structure yielded a 2.9-fold boost in per-active-site activity compared with that with a low curvature and high hydrophilic counterpart. Moreover, a NH3 Faradaic efficiency of 90.9 ± 2.3% was achieved with nearly 100% NO3- conversion. This high-curvature hydrophobic Cu dendrite was further integrated with a gas-extraction membrane, which demonstrated a comparable NH3 yield from the real reverse osmosis retentate brine.

Exploring the Complex Impact of Proteins on Dopamine Polymerization: Mechanisms and Strategies for Modulation.

Polydopamine (pDA) is a valuable material with wide-ranging potential applications. However, the complex and debated nature of dopamine polymerization complicates our understanding. Specifically, the impact of foreign substances, especially proteins, on pDA formation adds an additional layer of subtlety and complexity. This study delves into specific surface features of proteins that predominantly shape their impact on dopamine polymerization. Notably, the biotin-binding site emerges as a critical region responsible for the pronounced inhibitory effect of avidin and neutravidin on the dopamine polymerization process. The binding of biotin successfully mitigates these inhibitory effects. Moreover, several nucleases demonstrated a significant hindrance to pDA formation, with their impact substantially alleviated through the introduction of DNA. It is speculated that hydrogen bonding, electrostatic, cation-π, and/or hydrophobic interactions may underlie the binding between protein surfaces and diverse oligomeric intermediates formed by the oxidation products of dopamine. Additionally, we observed a noteworthy blocking effect on the dopamine polymerization reaction induced by erythropoietin (EPO), a glycoprotein hormone known for its role in stimulating red blood cell production and demonstrating neuroprotective effects. The inhibitory influence of EPO persisted even after deglycosylation. These findings not only advance our comprehension of the mechanisms underlying dopamine polymerization but also provide strategic insights for manipulating the reaction to tailor desired biomaterials.

Universal Design and Efficient Synthesis for High Ambipolar Mobility Emissive Conjugated Polymers.

High ambipolar mobility emissive conjugated polymers (HAME-CPs) are perfect candidates for organic optoelectronic devices, such as polymer light emitting transistors. However, due to intrinsic trade-off relationship between high ambipolar mobility and strong solid-state luminescence, the development of HAME-CPs suffers from high structural and synthetic complexity. Herein, a universal design principle and simple synthetic approach for HAME-CPs are developed. A series of simple non-fused polymers composed of charge transfer units, π bridges and emissive units are synthesized via a two-step microwave assisted C-H arylation and direct arylation polymerization protocol with high total yields up to 61 %. The synthetic protocol is verified valid among 7 monomers and 8 polymers. Most importantly, all 8 conjugated polymers have strong solid-state emission with high photoluminescence quantum yields up to 24 %. Furthermore, 4 polymers exhibit high ambipolar field effect mobility up to 10-2 cm2 V-1 s-1, and can be used in multifunctional optoelectronic devices. This work opens a new avenue for developing HAME-CPs by efficient synthesis and rational design.

Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signaling and airway inflammation.

RATIONALE: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of IFN-stimulated genes (ISGs). How asthma genetic susceptible genes modulate cellular response upon viral infection through fine-tuning ISGs induction and subsequent airway inflammation in genetically susceptible asthmatics remains largely unknown. OBJECTIVES: To decipher the functions of GSDMB in respiratory virus-induced lung inflammation. METHODS: In two independent cohorts, we analyzed expression correlation between GSDMB and ISGs. In human bronchial epithelial cell line or primary cells, we generated GSDMB-overexpressing and -deficient cells. A series of qPCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISGs induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and applied respiratory syncytial virus (RSV) infection to determine the role of GSDMB on RSV-induced lung inflammation in vivo. MEASUREMENTS AND MAIN RESULTS: Gasdermin B encoded by GSDMB, one of the most significant asthma-susceptible genes at 17q21, acts as a novel RNA sensor, promoting MAVS-TBK1 signaling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB gene in mouse airway epithelium leads to enhanced ISGs induction, increased airway inflammation with mucus hyper-secretion upon RSV infection. CONCLUSIONS: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.

Corrigendum: The influence of physical education courses integrated with civic education on prosocial behavior among college students: the chain mediating effect of cultural confidence and self-esteem.

[This corrects the article DOI: 10.3389/fpsyg.2023.1217290.].

Validation of the Mindray VS9 Vital Signs Monitor in a combined adult and pediatric population according to ISO Standard 81060-2:2018.

We aimed to validate the accuracy of the Mindray VS9 Vital Signs Monitor, which features the Mindray TrueBP inflation algorithm for oscillometric blood pressure (BP) measurement, to check if it complies with the International Organization for Standardization Standard (ISO 81060-2:2018) in a combined adult and pediatric population. A total of 86 participants, including both adult and pediatric subjects, were recruited. The distribution of their ages, gender, BPs and limb sizes all complied with the requirement of the ISO standard. The inflation and deflation algorithms were validated independently using the same-arm sequential BP measurement method. For each subject, the BP was first determined by two independent observers using a mercury sphygmomanometer (R1). The BP of the subject was then determined by the third observer using the test equipment (T1). Then, using a mercury sphygmomanometer, two independent observers were asked to determine the subject's BP (R2) again. R1-T1-R2 were considered a valid pair of data. This cycle continued until 3 pairs of valid data were achieved. We collected 258 pairs of valid BP data for the validation of the inflation and deflation algorithms respectively. For validation Criterion 1, the mean ± SD of the differences between the readings obtained from the test device and reference BP was 0.0 ±â€…6.6/-1.8 ±â€…7.1 mmHg (systolic/diastolic) when the deflation algorithm was used, and 2.4 ±â€…6.3/ 0.3 ±â€…6.9 mmHg (systolic/diastolic) when the inflation algorithm was used. For validation Criterion 2, the SD of the averaged BP differences between the test device and the reference BP per subject was 5.35/6.33 mmHg (systolic/diastolic) when the deflation algorithm was used, and 5.17/5.75 mmHg (systolic/diastolic) when the inflation algorithm was used. The VS9 Vital Signs Monitor fulfilled all the criteria in the ISO Standard. Moreover, the inflation algorithm had a shorter Measure Time (by 7-21 s) and lower maximum inflation pressure (by 9.7-22 mmHg). The VS9 Vital Signs Monitor fulfilled all the requirements of the ISO Standard (ISO 81060-2:2018) in a combined adult and pediatric population and is recommended for clinical use.

The brain-heart axis: Integrative analysis of the shared genetic etiology between neuropsychiatric disorders and cardiovascular disease.

BACKGROUND: Multiple observational studies have reported substantial comorbidity between neuropsychiatric disorders and cardiovascular disease (CVD), but the underlying mechanisms remain largely unknown. METHODS: Using GWAS summary datasets of 8 neuropsychiatric disorders and 6 cardiovascular diseases, an integrative analysis incorporating linkage-disequilibrium-score-regression (LDSC), Mendelian randomization (MR), functional mapping and annotation (FUMA), and functional enrichment analysis, was conducted to investigate shared genetic etiology of the brain-heart axis from the whole genome level, single-nucleotide polymorphism (SNP) level, gene level, and biological pathway level. RESULTS: In LDSC analysis, 18 pairwise traits between neuropsychiatric disorders and CVD were identified with significant genetic overlaps, revealing extensive genome-wide genetic correlations. In bidirectional MR analysis, 19 pairwise traits were identified with significant causal relationships. Genetic liabilities to neuropsychiatric disorders, particularly attention-deficit hyperactivity disorder and major depressive disorder, conferred extensive significant causal effects on the risk of CVD, while hypertension seemed to be a risk factor for multiple neuropsychiatric disorders, with no significant heterogeneity or pleiotropy. In FUMA analysis, 13 shared independent significant SNPs and 887 overlapping protein-coding genes were detected between neuropsychiatric disorders and CVD. With GO and KEEG functional enrichment analysis, biological pathways of the brain-heart axis were highly concentrated in neurotransmitter synaptic transmission, lipid metabolism, aldosterone synthesis and secretion, glutathione metabolism, and MAPK signaling pathway. CONCLUSION: Extensive genetic correlations and genetic overlaps between neuropsychiatric disorders and CVD were identified in this study, which might provide some new insights into the brain-heart axis and the therapeutic targets in clinical practice.

Asiatic acid and madecassic acid cause cardiotoxicity via inflammation and production of excessive reactive oxygen species in zebrafish.

Centella asiatica (L.) Urban is a famous Chinese traditional medicine, which is widely used for treating various chronic inflammatory diseases. Although there are reports that Centella total glycosides exhibit heart-protective properties, our previous experiment showed that it has cardiac toxic effects in zebrafish. The components of Centella total glycosides are complex, so we recommend further research to determine their key components and mechanisms. In this study, sample quantification was done using liquid chromatography-tandem mass spectrometry. The cardiotoxicity of Centella total glycosides, asiaticoside, madecassoside, asiatic acid, and madecassic acid was evaluated using zebrafish and cell models. The zebrafish oxidative stress model and myocarditis model were used to explore further the mechanisms through which cardiotoxicity is achieved. Asiatic acid and madecassic acid caused zebrafish cardiotoxicity and H9C2 cell death. However, no toxicity effects were observed for asiaticoside and madecassoside in zebrafish, until the solution was saturated. The results from the cell model study showed that asiatic acid and madecassic acid changed the expression of apoptosis-related genes in myocardial cells. In the zebrafish model, high concentrations of these components raised the levels of induced systemic inflammation, neutrophils gathered in the heart, and oxidative stress injury. Asiatic acid and madecassic acid are the main components causing cardiotoxicity in zebrafish. This may be due to enhanced inflammation and reactive oxygen species injury, which causes myocardial cell apoptosis, which further leads to cardiac toxicity.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

Superaerophobic/Superhydrophilic Multidimensional Electrode System for High-Current-Density Water Electrolysis.

Water electrolysis is emerging as a promising renewable-energy technology for the green production of hydrogen, which is a representative and reliable clean energy source. From economical and industrial perspectives, the development of earth-abundant non-noble metal-based and bifunctional catalysts, which can simultaneously exhibit high catalytic activities and stabilities for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), is critical; however, to date, these types of catalysts have not been constructed, particularly, for high-current-density water electrolysis at the industrial level. This study developed a heterostructured zero-dimensional (0D)-one-dimensional (1D) PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF)-Ni3S2 as a self-supported catalytic electrode via interface and morphology engineering. This unique heterodimensional nanostructure of the PBSCF-Ni3S2 system demonstrates superaerophobic/superhydrophilic features and maximizes the exposure of the highly active heterointerface, endowing the PBSCF-Ni3S2 electrode with outstanding electrocatalytic performances in both HER and OER and exceptional operational stability during the overall water electrolysis at high current densities (500 h at 500 mA cm-2). This study provides important insights into the development of catalytic electrodes for efficient and stable large-scale hydrogen production systems.

XBP1-mediated transcriptional regulation of SLC5A1 in human epithelial cells in disease conditions.

BACKGROUND: Sodium-Glucose cotransporter 1 and 2 (SGLT1/2) belong to the family of glucose transporters, encoded by SLC5A1 and SLC5A2, respectively. SGLT2 is almost exclusively expressed in the renal proximal convoluted tubule cells. SGLT1 is expressed in the kidneys but also in other organs throughout the body. Many SGLT inhibitor drugs have been developed based on the mechanism of blocking glucose (re)absorption mediated by SGLT1/2, and several have gained major regulatory agencies' approval for treating diabetes. Intriguingly these drugs are also effective in treating diseases beyond diabetes, for example heart failure and chronic kidney disease. We recently discovered that SGLT1 is upregulated in the airway epithelial cells derived from patients of cystic fibrosis (CF), a devastating genetic disease affecting greater than 70,000 worldwide. RESULTS: In the present work, we show that the SGLT1 upregulation is coupled with elevated endoplasmic reticulum (ER) stress response, indicated by activation of the primary ER stress senor inositol-requiring protein 1α (IRE1α) and the ER stress-induced transcription factor X-box binding protein 1 (XBP1), in CF epithelial cells, and in epithelial cells of other stress conditions. Through biochemistry experiments, we demonstrated that the spliced form of XBP1 (XBP1s) acts as a transcription factor for SLC5A1 by directly binding to its promoter region. Targeting this ER stress → SLC5A1 axis by either the ER stress inhibitor Rapamycin or the SGLT1 inhibitor Sotagliflozin was effective in attenuating the ER stress response and reducing the SGLT1 level in these cellular model systems. CONCLUSIONS: The present work establishes a causal relationship between ER stress and SGLT1 upregulation and provides a mechanistic explanation why SGLT inhibitor drugs benefit diseases beyond diabetes.

Sotagliflozin attenuates liver-associated disorders in cystic fibrosis rabbits.

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.

TMED2 promotes glioma tumorigenesis by being involved in EGFR recycling transport.

Aberrant epidermal growth factor receptor (EGFR) signaling is the core signaling commonly activated in glioma. The transmembrane emp24 protein transport domain protein 2 (TMED2) interacts with cargo proteins involved in protein sorting and transport between endoplasmic reticulum (ER) and Golgi apparatus. In this study, we found the correlation between TMED2 with glioma progression and EGFR signaling through database analysis. Moreover, we demonstrated that TMED2 is essential for glioma cell proliferation, migration, and invasion at the cellular levels, as well as tumor formation in mouse models, underscoring its significance in the pathobiology of gliomas. Mechanistically, TMED2 was found to enhance EGFR-AKT signaling by facilitating EGFR recycling, thereby providing the initial evidence of TMED2's involvement in the membrane protein recycling process. In summary, our findings shed light on the roles and underlying mechanisms of TMED2 in the regulation of glioma tumorigenesis and EGFR signaling, suggesting that targeting TMED2 could emerge as a promising therapeutic strategy for gliomas and other tumors associated with aberrant EGFR signaling.