Triglyceride Glucose Index and the Risk of Diabetic Nephropathy in Patients with Type 2 Diabetes: A Meta-Analysis.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aims to evaluate the association between the triglyceride glucose (TyG) index, a novel marker reflecting insulin resistance, and the risk of developing DN in patients with T2DM. We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases up to May 12, 2024. Studies assessing the TyG index in relation to DN risk among T2DM patients were included. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. A total of eight longitudinal follow-up studies encompassing 15 889 patients with T2DM were included. The pooled analysis revealed a significant association between a higher TyG index and an increased risk of DN in patients with T2DM (RR=1.53, 95% CI: 1.37-1.71, p<0.001; I2=35%). The results of meta-regression analysis suggested that the cutoff of TyG index was positively associated with the RR for the association between TyG index and DN. Subgroup analyses demonstrated that the association was stronger in studies with cutoff of TyG index ≥9.5 as compared to those with the cutoff <9.5 (RR: 1.73 vs. 1.40, p for subgroup difference <0.05). The association was not significantly affected by study design, mean age of the patients, proportion of men, or follow-up durations. In conclusion, higher TyG index is significantly associated with an increased risk of DN in patients with T2DM.

[Anti-breast cancer effect of a mitochondrion-targeted derivative of ergosterol peroxide in vitro and in vivo].

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

Insight into the Internal Structure of High-Performance Multicore Magnetic Nanoparticles Used in Cancer Thermotherapy.

Multicore magnetic nanoparticles (MNPs), comprising iron oxide cores embedded in a sugar or starch matrix, are a class of nanomaterials with promising magnetic heating properties. Their internal structure, and particularly the strength of the internal core-core magnetic interactions, are believed to determine the functional properties, but there have been few detailed studies on this to date. We report here on an interlaboratory and multimodality transmission electron microscopy (TEM) and magnetic study of a high-performance MNP material (supplied by Resonant Circuits Limited, RCL) that is currently being used in a clinical study for the treatment of pancreatic cancer. TEM data were collected under a variety of conditions: conventional; high-resolution; scanning; cryogenic; and, for the first time, liquid phase. All the imaging modes showed mostly irregular dextran lamellae of lateral dimensions 30-90 nm, plus ca. 15% n/n of what appeared to be 30-60 nm long "nanorods", and a multitude of well-dispersed ca. 3.7 nm diameter iron oxide cores. Cryogenic electron tomography indicated that the nanorods were edge-on lamellae, but in dried samples, tomography showed rod- or lath-shaped forms, possibly resulting from the collapse of lamellae during drying. High-resolution TEM (HRTEM) showed the dextran to be crystallized in the low-temperature hydrated dextran polymorph. Magnetic remanence Henkel-plot analysis indicated a weak core-core interaction field of ca. 4.8 kA/m. Theoretical estimates using a point-dipole model associated this field with a core-to-core separation distance of ca. 5 nm, which tallies well with the ca. 4-6 nm range of separation distances observed in liquid-cell TEM data. On this basis, we identify the structure-function link in the RCL nanoparticles to be the unusually well-dispersed multicore structure that leads to their strong heating capability. This insight provides an important design characteristic for the future development of bespoke nanomaterials for this significant clinical application.

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate.

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b, composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.

Roles of Nonadiabatic Processes, Reaction Mechanism, and Selectivity in Cu-Catalyzed [2 + 2] Photocycloaddition of Norbornene and Acetone to Oxetane.

Oxetane has been extensively studied for its applications in medicinal chemistry and as a reactive intermediate in synthesis. Experiments report a Cu-catalyzed [2 + 2] photocycloaddition of acetone and norbornene to oxetane, which is proposed to deviate from the conventional Paternò-Büchi reaction. However, its mechanism at the atomic level is not clear. In this study, we used a combination of multistate complete active space second-order perturbation theory (MS-CASPT2) and density functional theory to systematically investigate the reaction mechanism and elucidate the factors contributing to the diastereomeric selectivity. Initially, the formation of the TpCu(Norb) complex is achieved by strong interaction between tris(pyrazolyl)borate Cu(I) (TpCu) and norbornene in the ground state (S0). Upon photoexcitation, TpCu(Norb) eventually decays to the T1 state, in which TpCu(Norb) attacks acetone to initiate subsequent reactions and produces final endo- or exo-oxetane products. All these reactions initially involve the C-C bond formation in the T1 state thereto leading to a ring-opening intermediate. This intermediate then undergoes a nonradiative transition to the S0 state, producing a five-membered ring intermediate, from which the C-O bond is formed, leading to the experimentally dominant exo-product. In contrast, the endo-oxetane formation requires a rearrangement process after the C-C bond is formed because of the large steric effects. As a consequence, the different reaction pathways generating exo- and endo-products exhibit large differences in the free-energy barriers, which results in a diastereomeric selectivity observed experimentally. Additionally, the nonradiative transition is found to play an important role in facilitating these reaction steps. The present computational study provides valuable mechanistic insights into Cu-catalyzed photocycloaddition reactions.

Datasets of fungal diversity and pseudo-chromosomal genomes of mangrove rhizosphere soil in China.

With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences. We describe twelve newly assembled genomes, including four chromosomal-level genomes of fungal isolates from the mangrove ecosystems coupled with functional annotations. We envisage that these data will be of value for future studies including comparative genome analysis and large-scale temporal and/or spatial research to elucidate the potential mechanisms by which mangrove fungal communities assemble and evolve. We further anticipate that the genomes represent valuable resources for bioprospecting related to industrial or clinical uses.

Comparison of the Immunogenicity of the LZ901 Vaccine and HZ/su Vaccine in a Mouse Model.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

Mycobacterium gordoniasis of the cervical lymph nodes: A case report.

BACKGROUND: Owing to the advancement in bacterial identification techniques, the detection rate of non-tuberculous mycobacterium (NTM) has been on the rise. Different from Mycobacterium tuberculosis, the clinical symptoms of NTM are not easily detected, and the clinical efficacy and prognosis are somewhat heterogeneous. To report a case of Mycobacterium gordoniasis of cervical lymph node diagnosed in Anhui Chest Hospital in July 2022. CASE SUMMARY: Upon examination, the patient who weighed 67.5 kg, was human immunodeficiency virus negative, healthy, without hypertension, diabetes, heart disease and other basic diseases microscopic analysis revealed granulomatous inflammation with coagulation necrosis in the lymphocyte, and tuberculosis was not ruled out. Plain computed tomography scans of the neck and chest indicated the presence of a single grayish-yellow and grayish-brown tissue, the dimensions of which was top of form 10.5 cm × 3.0 cm × 1.5 cm. After pathological consultation in our hospital, the diagnosis was confirmed as NTM infection. CONCLUSION: This case report and the clinical epidemiological research on improving NTM have important guiding significance for improving decision-making in clinical treatments.

A record-high EQE of 7.65%@3300 cd m-2 achieved in non-doped near-ultraviolet OLEDs based on novel D'-D-A type bipolar fluorophores upon molecular configuration engineering.

Developing a high-performance near-ultraviolet (NUV) material and its simple non-doped device with a small efficiency roll-off and good color purity is a promising but challenging task. Here, we proposed a novel donor'-donor-acceptor (D'-D-A) type molecular strategy to largely solve the intrinsic contradictions among wide-bandgap NUV emission, fluorescence efficiency, carrier injection and transport. An efficient NUV fluorophore, 3,6-mPPICNC3, exhibiting a hybridized local and charge-transfer state, is achieved through precise molecular configuration engineering, realizing similar hole and electron mobilities at both low and high electric fields. Moreover, the planarized intramolecular charge transfer excited state and steric hindrance effect endow 3,6-mPPICNC3 with a considerable luminous efficiency and good color purity in the aggregation state. Consequently, the non-doped device emitting stable NUV light with Commission Internationale de l'Eclairage (CIE) coordinates of (0.160, 0.032) and a narrow full width at half maximum of 44 nm exhibits a state-of-the-art external quantum efficiency (EQE) of 7.67% and negligible efficiency roll-off over a luminance range from 0 to 3300 cd m-2. This is a record-high efficiency among all the reported non-doped NUV devices. Amazingly, an EQE of 7.85% and CIE coordinates of (0.161, 0.025) are achieved in the doped device. This demonstrates that the D'-D-A-type molecular structure has great potential for developing high-performance organic light-emitting materials and their optoelectronic applications.

Telehealth With Comprehensive Live-Fed Real-World Data as a Patient Care Platform for Lung Cancer: Implementation and Evaluation Study.

BACKGROUND: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. OBJECTIVE: The primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician's perspective. METHODS: A telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform's registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. RESULTS: Over a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. CONCLUSIONS: This study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

Self-assembling dendrimer nanosystems for specific fluorine magnetic resonance imaging and effective theranostic treatment of tumors.

Fluorine magnetic resonance imaging (19F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19F-MRI. Importantly, the self-assembling 19F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19F-MRI and multimodal 19F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry.

Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants.

OBJECTIVE: Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination. METHODS: A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. RESULTS: Neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals. CONCLUSIONS: Our results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.

Strategy to prevent calcification by restricting surface adhesion of Ca2+: Reduced affinity of extracellular polymeric substances for Ca2+ by mild acidic conditions.

Controlling CaCO3 precipitation within anaerobic granular sludge (AnGS) is crucial for the anaerobic treatment of paper recycling wastewater. A viable strategy was proposed to control calcification by adjusting a mild acidic condition in an anaerobic reactor without hindering organic degradation. The results indicated that lowering the bulk pH (6.5 to 6.8) reduced calcium precipitation by 60.1 % in calcium-rich influent (Ca2+ 1200 mg/L) and eradicated CaCO3 deposition on AnGS. Extracellular polymeric substances (EPS) have proven to be crucial participants in Ca2+ migration. The acidic solution weakens the interactions between EPS and Ca2+ and then diminishes the EPS adsorption capacity and affinity for Ca2+. The mild acidic environment goes beyond reducing CaCO3 formation in wastewater. EPS protonation reduced the probability of Ca2+ adhering to the AnGS surface, which halted calcium transportation from bulk liquid to granule. This work offers a feasible strategy to prevent AnGS calcification in high-calcium wastewater.

Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

Pre-drying limitedly affected the yield, fuel properties, pyrolysis and combusion behavior of sewage sludge hydrochar.

While pre-drying of sewage sludge prior to hydrothermal carbonization is rarely practiced, various pre-drying methods have been performed in literature at lab-scale for convenient solid-to-liquid ratio adjustment. This has created a barrier for comparing hydrochar quality between different studies. Given pre-drying can destroy the floc structure of sewage sludge, we hypothesize that pre-drying may promote the hydrolysis step during hydrothermal carbonization process, resulting in improved hydrochar quality with low nitrogen content. In the current study, the influence of different pre-drying methods (freeze-dry, air-dry and vacuum-dry at 70 °C and 105 °C) on the subsequent hydrothermal carbonization of sewage sludge at 220 °C was assessed in terms of sewage sludge and hydrochar's chemical composition, fuel properties, pyrolysis and combustion behavior, as well as the characterization of the liquid phase. The results indicate that although pre-drying impacts sewage sludge's chemical composition, pyrolysis and combustion behavior, no significant differences exist in the yield, chemical composition, fuel properties, and pyrolysis and combustion behavior of the hydrochar. Therefore, the use of pre-drying would not affect the hydrothermal carbonization process of sewage sludge, and a comparison can be made on hydrochar quality between different studies with or without pre-drying.

Functional vertical connectivity of microbial communities in the ocean.

Sinking particles are a critical conduit for the transport of surface microbes to the ocean's interior. Vertical connectivity of phylogenetic composition has been shown; however, the functional vertical connectivity of microbial communities has not yet been explored in detail. We investigated protein and taxa profiles of both free-living and particle-attached microbial communities from the surface to 3000 m depth using a combined metaproteomic and 16S rRNA amplicon sequencing approach. A clear compositional and functional vertical connectivity of microbial communities was observed throughout the water column with Oceanospirillales, Alteromonadales, and Rhodobacterales as key taxa. The surface-derived particle-associated microbes increased the expression of proteins involved in basic metabolism, organic matter processing, and environmental stress response in deep waters. This study highlights the functional vertical connectivity between surface and deep-sea microbial communities via sinking particles and reveals that a considerable proportion of the deep-sea microbes might originate from surface waters and have a major impact on the biogeochemical cycles in the deep sea.

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway.

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Circulating galectin-3 level association with cardiovascular risk factors during peritoneal dialysis.

OBJECTIVE: Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients. METHODS: In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann-Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3. RESULTS: In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels. CONCLUSIONS: Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients.

A comprehensive review of the mechanisms on fish stress affecting muscle qualities: Nutrition, physical properties, and flavor.

Fish inevitably face numerous stressors in growth, processing, and circulation. In recent years, stress-related change in fish muscle quality has gradually become a research hotspot. Thus, the understanding of the mechanism regarding the change is constantly deepening. This review introduces the physiological regulation of fish under stress, with particular attention devoted to signal transduction, gene expression, and metabolism, and changes in the physiological characteristics of muscular cells. Then, the influences of various stressors on the nutrition, physical properties, and flavor of the fish muscle are sequentially described. This review emphasizes recent advances in the mechanisms underlying changes in muscle quality, which are believed to be involved mainly in physiological regulation under stress. In addition, studies are also introduced on improving muscle quality by mitigating fish stress.

Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BACKGROUND: Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. METHODS: We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. RESULT: Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. CONCLUSIONS: Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.