Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

Integrated Exploration of Epigenetic Dysregulation Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression and Prognosis in Hepatocellular Carcinoma.

Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.

Comparative efficacy and safety of all kinds of intraocular lenses in presbyopia-correcting cataract surgery: a systematic review and meta-analysis.

PURPOSE: To assess the efficacy and safety of various intraocular lenses (IOLs), including standard monofocal, bifocal, trifocal, extended depth of focus (EDOF), and enhanced monofocal IOLs, post-cataract surgery through a network meta-analysis. METHODS: A systematic search of PubMed, Cochrane Library, and Web of Science was conducted to identify relevant studies from the past 5 years. Parameters such as binocular visual acuities, spectacle independence, contrast sensitivity (CS), and optical quality were used to evaluate efficacy and safety. Data from the selected studies were analyzed using Review Manager 5.4 and STATA 17.0 software. RESULTS: Twenty-eight Randomized Controlled Trials (RCTs) comprising 2465 subjects were included. Trifocal IOLs exhibited superior uncorrected near visual acuity (UNVA) compared to monofocal IOLs (MD: -0.35; 95% CI: -0.48, -0.22). Both trifocal (AcrySof IQ PanOptix IOLs group MD: -0.13; 95% CI: -0.21, -0.06) and EDOF IOLs (MD: -0.13; 95% CI: -0.17, -0.09) showed better uncorrected intermediate visual acuity (UIVA) than monofocal IOLs. Trifocal IOLs ranked highest in spectacle independence at various distances (AT LISAtri 839MP group: SUCRA 97.5% for distance, 80.7% for intermediate; AcrySof IQ PanOptix group: SUCRA 83.0% for near). CONCLUSIONS: For cataract patients who want to treat presbyopia, trifocal IOLs demonstrated better visual acuity and spectacle independence at near distances. Different types of trifocal IOL characteristics differ. EDOF and enhanced monofocal IOLs have improved visual quality at intermediate distances.Therefore, It is very important to select the appropriate IOLs based on the lens characteristics and patient needs.

Choroid plexus enlargement in amyotrophic lateral sclerosis patients and its correlation with clinical disability and blood-CSF barrier permeability.

BACKGROUND: Using in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients. METHODS: In this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup. RESULTS: We found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients. CONCLUSION: Our study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.

Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS.

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

Accurate assembly of thiophene-bridged titanium-oxo clusters with photocatalytic amine oxidation activity.

Designing and synthesizing well-defined crystalline catalysts for the photocatalytic oxidative coupling of amines to imines remains a great challenge. In this work, a crystalline dumbbell-shaped titanium oxo cluster, [Ti10O6(Thdc)(Dmg)2(iPrO)22] (Ti10, Thdc = 2,5-thiophenedicarboxylic acid, Dmg = dimethylglyoxime, iPrOH = isopropanol), was constructed through a facile one-pot solvothermal strategy and treated as a catalyst for the photocatalytic oxidative coupling of amines. In this structure, Thdc serves as the horizontal bar, while the {Ti5Dmg} layers on each side act as the weight plates. The molecular structure, light absorption, and photoelectrochemical properties of Ti10 were systematically investigated. Remarkably, the inclusion of the Thdc ligand, with the assistance of the Dmg ligand, broadens the light absorption spectrum of Ti10, extending it into the visible range. Furthermore, the effective enhancement of charge transfer within the Ti10 was achieved with the successful incorporation of the Thdc ligand, as opposed to PTC-211, where terephthalic acid replaces the Thdc ligand, while maintaining consistency in other aspects of Ti10. Building on this foundation, Ti10 was employed as a heterogeneous molecular photocatalyst for the catalytic oxidative coupling reaction of benzylamine (BA), demonstrating very high conversion activity and selectivity. Our study illustrates that the inclusion of ligands derived from Thdc enhances the efficiency of charge transfer in functionalized photocatalysts, significantly influencing the performance of photocatalytic organic conversion.

Macro-meso damage characteristics of coal body under different pressure relief conditions.

The mining of the protective coal seam usually produces different pressure relief effects on the different areas of protected coal seam, the reason is that the stress paths of protected seam coal body in different areas caused by mining effect are different. In order to explore the differential pressure relief damage effect of coal body under different pressure relief conditions, the stress evolution path of coal body in different areas of the protected coal seam is obtianed by using theoretical analysis and the macro-micro damage characteristics of coal body under different stress paths by using numerical simulation in this paper. The results show that: The damage characteristics of the sample models are basically the same in the in-situ stress recovery stage and the mining disturbance stage of the two stress paths. With ith the sequence of stress stages experienced by the sample model, the distribution of acoustic emission events concentrates in the high-intensity area and the porosity continues to decrease. The number of cracks increases slowly in the stage of in-situ stress recovery stage, most of which are tensile cracks, while the number of cracks increases sharply in the mining disturbance stage, most of which are shear cracks. The difference of the deformation and macro meso damage characteristics of the sample models under the two stress paths is mainly reflected in the post mining pressure relief stage. At the post mining pressure relief stage of path 1, the number of cracks in the sample has little growth, and most of them are small energy tensile cracks, and the porosity increases, which verifies its obvious pressure relief activation antireflection effect; At this stage of path 2, the crack growth of the sample is obvious, and most of them are high-energy shear cracks, and the porosity continues to decrease. Compared with path 1, the pressure relief expansion effect of the sample model is suppressed and the compression damage continues to develop in this stage of path 2.

Nitrogen-Anchored Boridene Enables Mg-CO2 Batteries with High Reversibility.

Nanoscale defect engineering plays a crucial role in incorporating extraordinary catalytic properties in two-dimensional materials by varying the surface groups or site interactions. Herein, we synthesized high-loaded nitrogen-doped Boridene (N-Boridene (Mo4/3(BnN1-n)2-mTz), N-doped concentration up to 26.78 at %) nanosheets by chemical exfoliation followed by cyanamide intercalation. Three different nitrogen sites are observed in N-Boridene, wherein the site of boron vacancy substitution mainly accounts for its high chemical activity. Attractively, as a cathode for Mg-CO2 batteries, it delivers a long-term lifetime (305 cycles), high-energy efficiency (93.6%), and ultralow overpotential (∼0.09 V) at a high current of 200 mA g-1, which overwhelms all Mg-CO2 batteries reported so far. Experimental and computational studies suggest that N-Boridene can remarkably change the adsorption energy of the reaction products and lower the energy barrier of the rate-determining step (*MgCO2 → *MgCO3·xH2O), resulting in the rapid reversible formation/decomposition of new MgCO3·5H2O products. The surging Boridene materials with defects provide substantial opportunities to develop other heterogeneous catalysts for efficient capture and converting of CO2.

The combination of Brassica rapa L. polysaccharides and cisplatin enhances the anti liver cancer effect and improves intestinal microbiota and metabolic disorders.

Polysaccharides are commonly used as low-toxicity anticancer active substances to enhance the chemotherapeutic effect of cisplatin and reduce toxicity. Brassica rapa L. polysaccharides have been shown to have hepatoprotective effects; however, their anticancer effects in combination with cisplatin and their mechanisms have not been reported. An acidic polysaccharide from Brassica rapa L. (BRCPe) using hydroalcohol precipitation-assisted sonication was Characterized. The effects of BRCPe combined with cisplatin treatment on tumor growth in hepatocellular carcinoma mouse model were investigated. The impact of the combined treatment on the composition of intestinal flora, levels of short-chain fatty acids and endogenous metabolites in tumor mice were analyzed based on macrogenomic and metabolomic data Our results showed that the BRCPe combined with low-dose Cisplatin group showed better inhibitory activity against hepatocellular carcinoma cell growth in terms of tumor volume, tumor weight, and tumor suppression rate compared with the BRCPe and Cisplation alone group, and reduced the side effects of cisplatin-induced body weight loss, immune deficiency, and liver injury. Furthermore, BRCPe combined with cisplatin was found to induce apoptosis in hepatocellular carcinoma cell through the activation of the caspase cascade reaction. In addition, the intervention of BRCPe were observed to modulate the composition, structure and functional structure of intestinal flora affected by cisplatin. Notably, Lachnospiraceae bacteria, Lactobacillus murinus, Muribaculaceae, and Clostridiales bacteria were identified as significant contributors to microbial species involved in metabolic pathways. Moreover, BRCPe effectively regulate the metabolic disorders in cisplatin-induced hepatocellular carcinoma mice. In conclusion, BRCPe could potentially function as an adjuvant or dietary supplement to augment the effectiveness of cisplatin chemotherapy through the preservation of a more efficient intestinal microenvironmental homeostasis.

Prediction Model of Lean Coal Adsorption of Power Plant Flue Gas.

To minimize errors in calculating coal flue gas adsorption capacity due to gas compressibility and to preclude prediction inaccuracies in abandoned mine flue gas storage capacity for power plants, it is imperative to account for the influence of compression factor calculation accuracy while selecting the optimal theoretical adsorption model. In this paper, the flue gas adsorption experiment of a power plant with coal samples gradually pressurized to close to 5 MPa at two different temperatures is carried out, and the temperature and pressure data obtained from the experiment are substituted into five different compression factor calculation methods to calculate different absolute adsorption amounts. The calculated adsorption capacities were fitted into six theoretical adsorption models to establish a predictive model suitable for estimating the coal adsorption capacity in power plant flue gas. Results reveal significant disparities in the absolute adsorption capacity determined by different compression factors, with an error range of 0.001278-7.8262 (cm3/kg). The Redlich-Kwong equation of state emerged as the most suitable for the flue gas of the selected experimental coal sample and the chosen composition ratio among the five compression factors. Among the six theoretical adsorption models, the Brunauer-Emmett-Teller model with three parameters demonstrated the highest suitability for predicting the adsorption capacity of coal samples in power plant smoke, achieving a fitting accuracy as high as 0.9922 at 49.7 °C.

A novel IgE epitope-specific antibodies-based sandwich ELISA for sensitive measurement of immunoreactivity changes of peanut allergen Ara h 2 in processed foods.

Background: Peanut is an important source of dietary protein for human beings, but it is also recognized as one of the eight major food allergens. Binding of IgE antibodies to specific epitopes in peanut allergens plays important roles in initiating peanut-allergic reactions, and Ara h 2 is widely considered as the most potent peanut allergen and the best predictor of peanut allergy. Therefore, Ara h 2 IgE epitopes can serve as useful biomarkers for prediction of IgE-binding variations of Ara h 2 and peanut in foods. This study aimed to develop and validate an IgE epitope-specific antibodies (IgE-EsAbs)-based sandwich ELISA (sELISA) for detection of Ara h 2 and measurement of Ara h 2 IgE-immunoreactivity changes in foods. Methods: DEAE-Sepharose Fast Flow anion-exchange chromatography combining with SDS-PAGE gel extraction were applied to purify Ara h 2 from raw peanut. Hybridoma and epitope vaccine techniques were employed to generate a monoclonal antibody against a major IgE epitope of Ara h 2 and a polyclonal antibody against 12 IgE epitopes of Ara h 2, respectively. ELISA was carried out to evaluate the target binding and specificity of the generated IgE-EsAbs. Subsequently, IgE-EsAbs-based sELISA was developed to detect Ara h 2 and its allergenic residues in food samples. The IgE-binding capacity of Ara h 2 and peanut in foods was determined by competitive ELISA. The dose-effect relationship between the Ara h 2 IgE epitope content and Ara h 2 (or peanut) IgE-binding ability was further established to validate the reliability of the developed sELISA in measuring IgE-binding variations of Ara h 2 and peanut in foods. Results: The obtained Ara h 2 had a purity of 94.44%. Antibody characterization revealed that the IgE-EsAbs recognized the target IgE epitope(s) of Ara h 2 and exhibited high specificity. Accordingly, an IgE-EsAbs-based sELISA using these antibodies was able to detect Ara h 2 and its allergenic residues in food samples, with high sensitivity (a limit of detection of 0.98 ng/mL), accuracy (a mean bias of 0.88%), precision (relative standard deviation < 16.50%), specificity, and recovery (an average recovery of 98.28%). Moreover, the developed sELISA could predict IgE-binding variations of Ara h 2 and peanut in foods, as verified by using sera IgE derived from peanut-allergic individuals. Conclusion: This novel immunoassay could be a user-friendly method to monitor low level of Ara h 2 and to preliminary predict in vitro potential allergenicity of Ara h 2 and peanut in processed foods.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non-motor symptoms in patients with Parkinson's disease.

BACKGROUND: This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). METHODS: The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). RESULTS: Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. CONCLUSIONS: The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

Value of serum brain-derived neurotrophic factor and glial fibrillary acidic protein for detecting depression in patients with Helicobacter pylori infection.

OBJECTIVE: Infection with helicobacter pylori (H. pylori) is associated with depression, and depression can affect the outcome of H. pylori treatment. This study aimed to evaluate the value of serum brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) for predicting depression in H. pylori-positive patients. METHOD: A total of 82H. pylori-positive and 82H. pylori-negative patients were recruited for this study. All patients underwent neuropsychological and gastrointestinal assessments and blood sampling. BDNF and GFAP levels were measured in serum. The least absolute shrinkage and selection operator (LASSO) model was used to determine a composite marker. RESULTS: H. pylori-positive patients showed significantly increased serum GFAP levels and significantly decreased serum BDNF levels compared to H. pylori-negative patients. Among H. pylori-positive patients, serum levels of gastrin 17 (G-17), pepsinogen (PG) I/PGII, BDNF, and GFAP, as well as Gastrointestinal Symptom Rating Scale (GSRS) scores, were significantly correlated with Hamilton Depression Scale (HAMD-24) overall scores and factor scores. Interactions between serum BDNF/GFAP and gastrointestinal serum indices or GSRS scores were significantly associated with HAMD-24 scores in H. pylori-positive patients. The LASSO model indicated that the combination of serum BDNF, GFAP, and G-17 and GSRS scores could identify H. pylori-positive patients with depression with an area under the curve of 0.879. CONCLUSION: Circulating changes in BDNF and GFAP were associated with the occurrence of depression in H. pylori-positive patients. A composite marker including neural and gastrointestinal function-related indices may be of value for identifying depression among H. pylori-positive patients.

Consumption of Apigenin Prevents Radiation-induced Gut Dysbiosis in Male C57BL/6J Mice Exposed to Silicon Ions.

The search for medical treatments to prevent radiation-induced damage to gastrointestinal tissue is crucial as such injuries can be fatal. This study aimed to investigate the effects of apigenin (AP) on the gut microbiome of irradiated mice, as it is a promising radiation countermeasure. Male C57BL/6J mice were divided into four groups, with six mice in each group. Two groups were given food with apigenin (20 mg/kg body weight or AP 20) before and after exposure to 0 or 50 cGy of silicon (28Si) ions, while another two groups of mice received regular diet without apigenin (0 mg/kg body weight or AP 0) before and after irradiation. The duodenum, the primary site for oral AP absorption, was collected from each mouse seven days after radiation exposure. Using 16S rRNA amplicon sequencing, we found significant differences in microbial diversity among groups. Firmicutes and Bacteroidetes were the major phyla for all groups, while actinobacterial and proteobacterial sequences represented only a small percentage. Mice not given dietary apigenin had a higher Firmicutes and Bacteroidetes (F/B) ratio and an imbalanced duodenal microbiota after exposure to radiation, while irradiated mice given apigenin had maintained homeostasis of the microbiota. Additionally, irradiated mice not given apigenin had decreased probiotic bacteria abundance and increased inflammation, while apigenin-supplemented mice had reduced inflammation and restored normal histological structure. In conclusion, our results demonstrate the potential of dietary apigenin as a countermeasure against radiation-induced gut injuries due to its anti-inflammatory activity, reduction of gut microbiota dysbiosis, and increase in probiotic bacteria (e.g., Lachnospiraceae, Muribaculaceae and Bifidobacteriaceae).

Serine Supports Epithelial and Immune Cell Function in Colitis.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity; mucosal healing is critical for remission. Serine is a nonessential amino acid that supports epithelial and immune cell metabolism and proliferation; however, whether these roles affect IBD pathogenesis is not well understood. Here, we show that serine synthesis increases selectively in the epithelial cells of colons from patients with IBD and murine models of colitis. Inhibiting serine synthesis impairs colonic mucosal healing and increases susceptibility to acute injury in mice, effects associated with impaired epithelial cell proliferation. Dietary removal of serine similarly sensitizes mice to acute chemically induced colitis but ameliorates inflammation in chronic colitis models. The anti-inflammatory effect of exogenous serine depletion in chronic colitis is associated with mitochondrial dysfunction of macrophages, resulting in impaired nucleotide production and proliferation. Collectively, these results suggest that serine plays an important role in both epithelial and immune cell biology in the colon and that modulating its availability could affect IBD pathogenesis.

Development and Immunological Evaluation of a Multiantigen Thermostable Nanovaccine Adjuvanted with T-Cell-Activating Scaffold for African Swine Fever.

African swine fever is an acute and highly contagious infectious disease with a mortality rate of up to 100%. The lack of commercial vaccines and drugs is a serious economic threat to the global pig industry. Cell-mediated immunity plays an essential role in protection against viral infection. We previously reported the rational design of a T-cell-activating thermostable scaffold (RPT) for antigen delivery and improved cellular immunity. We conjugated antigens P30, P54, P72, CD2 V, and CP312R to RPT, using a SpyCatcher/SpyTag covalent attachment strategy to construct nanovaccines (multiantigens-RPT). Multiantigens-RPT exhibited significantly higher thermal, storage, and freeze-thaw stability. The specific antibodies IgG and IgG2a of the multiantigen-RPT-immunized were higher than the antigens cocktail-immunized by approximately 10-100 times. ELISpot demonstrated that more IFN-γ-secreting cells were produced by the multiantigen-RPT-immunized than by the antigens cocktail-immunized. Delivery of the multiantigen nanovaccine by a T-cell-activating scaffold induced strong humoral and cellular immune responses in mice and pigs and is a potentially useful candidate vaccine for the African swine fever virus.

New clerodane diterpenoids from Callicarpa pseudorubella and their antitumor proliferative activity.

Six previously undescribed clerodane diterpenes, cardorubellas A-F (1-6), along with seven known ones (7-13), were isolated from the aerial parts of Callicarpa pseudorubella. Their chemical structures were established by analysis of 1D and 2D NMR, HR-ESI-MS, X-ray diffraction, and electronic circular dichroism (ECD) data. Notably, cardorubella B (2) represented the first examples of naturally occurring succinic anhydride-containing clerodane diterpenes derivatives. The anti-proliferative activities of these compounds were assessed. Remarkably, compound 2 exhibited comparable inhibitory activity against HEL cell lines, surpassing the positive control with an IC50 value of 14.01 ± 0.77 µM, compared to 17.02 ± 4.70 µM for 5-fluorouracil.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Insulin receptor alternative splicing in breast and prostate cancer.

Cancer etiology represents an intricate, multifactorial orchestration where metabolically associated insulin-like growth factors (IGFs) and insulin foster cellular proliferation and growth throughout tumorigenesis. The insulin receptor (IR) exhibits two splice variants arising from alternative mRNA processing, namely IR-A, and IR-B, with remarkable distribution and biological effects disparities. This insightful review elucidates the structural intricacies, widespread distribution, and functional significance of IR-A and IR-B. Additionally, it explores the regulatory mechanisms governing alternative splicing processes, intricate signal transduction pathways, and the intricate association linking IR-A and IR-B splicing variants to breast and prostate cancer tumorigenesis. Breast cancer and prostate cancer are the most common malignant tumors with the highest incidence rates among women and men, respectively. These findings provide a promising theoretical framework for advancing preventive strategies, diagnostic modalities, and therapeutic interventions targeting breast and prostate cancer.