Exploration of N6-methyladenosine modification in ascorbic acid 2-glucoside constructed stem cell sheets.

The aim of this study was to explore the mechanism of bone marrow stem cells (BMSCs) sheets constructed with different doses of Ascorbic acid 2-glucoside (AA-2G) in conjunction with N6-methyladenosine (m6A)-associated epigenetic genes analysing transcriptome sequencing data. Experimental groups of BMSCs induced by different AA-2G concentrations were set up, and the tissue structures were observed by histological staining of cell slices and scanning electron microscopy. Expression patterns of DEGs were analysed using short-time sequence expression mining software, and DEGs associated with m6A were selected for gene ontology analysis and pathway analysis. The protein-protein interaction (PPI) network of DEGs was analysed and gene functions were predicted using the search tool of the Retrieve Interacting Genes database. There were 464 up-regulated DEGs and 303 down-regulated DEGs between the control and high-dose AA-2G treatment groups, and 175 up-regulated DEGs and 37 down-regulated DEGs between the low and high-dose AA-2G treatment groups. The profile 7 exhibited a gradual increase in gene expression levels over AA-2G concentration. In contrast, profile 0 exhibited a gradual decrease in gene expression levels over AA-2G concentration. In the PPI network of m6A-related DEGs in profile 7, the cluster of metallopeptidase inhibitor 1 (Timp1), intercellular adhesion molecule 1 (Icam1), insulin-like growth factor 1 (Igf1), matrix metallopeptidase 2 (Mmp2), serpin family E member 1 (Serpine1), C-X-C motif chemokine ligand 2 (Cxcl2), galectin 3 (Lgals3) and angiopoietin-1 (Angpt1) was the top hub gene cluster. The expression of all hub genes was significantly increased after AA-2G intervention (P < 0.05), and the expression of Igf1 and Timp1 increased with increasing intervention concentration. The m6A epigenetic modifications were involved in the AA-2G-induced formation of BMSCs. Igf1, Serpine1 and Cxcl2 in DEGs were enriched for tissue repair, promotion of endothelial and epithelial proliferation and regulation of apoptosis.

Increased ferroptosis of erythrocytes is associated with myelodysplastic syndromes.

Anemia is the most common symptom in patients with myelodysplastic syndromes (MDS). Programmed cell death of erythrocytes is one of the contributing factors to anemia. Ferroptosis is a newly identified form of iron-dependent cell death. The aim of this study is to investigate whether anemia in MDS patients is associated with ferroptosis of nucleated erythrocytes(NEs).We detected lipid peroxidation levels, Fe2+ contents, cell death rates, glutathione (GSH) and malondialdehyde (MDA) levels in bone marrow CD235a+ NEs of MDS patients. Expression levels of ferroptosis-related molecules (ACSL4, GPX4, and SLC7A11) were evaluated through qRT-PCR and Western Blotting. Correlation between these markers and clinical parameters were analyzed. To further substantiate that the mode of cell death with CD235a+ NEs of MDS patients was attributed to the ferroptosis pathway, we applied Fer-1 to inhibit ferroptosis. Cell viability was assessed using CCK8, and changes in ferroptosis-related indicators were simultaneously evaluated. We discover that the ferroptosis level of bone marrow NEs in MDS patients was increased, which is related to anemia and iron overload. Ferroptosis might be one of the causes of anemia in MDS patients.

Constructing homo/hetero-nuclear carbon and oxygen atoms co-doped graphitic carbon nitride assisted by ionic liquid for photothermal synergistic catalytic oxidation of cyclohexane.

The adoption of photothermal synergistic catalysis for cyclohexane oxidation can balance the advantages of high conversion of thermal catalysis and high selectivity of photocatalytic technology to achieve better catalytic performance. Here, we prepared functional carbon nitride (BCA-CN) by self-assembly strategy of ionic liquid [Bmim]CA (1-Butyl-3-methylimidazole citrate) with melamine and cyanuric acid utilizing abundant elements and anionic/cationic hydrogen bonding interactions. The introduction of [Bmim]CA embeds C-C (carbon and carbon band) and C-O-C (ether bond) structures into graphitic carbon nitride (g-C3N4) framework, significantly improving light absorption capacity and migration of photo generated charge carriers. Compared to g-C3N4, both BCA-CN increases cyclohexane conversion and KA oil (the mixture of cyclohexanol and cyclohexanone) selectivity by 1.3 times under photothermal catalysis. The surface reactions are facilitated by changing adsorption sites of cyclohexane to increase adsorption energy and obtaining more hydroxyl radicals and superoxide radicals. Furthermore, the enhanced selectivity is attributed to the difficulty in generating cyclohexanone radicals. This work offers the reference scheme for the development of efficient photothermal catalysts in the selective oxidation of cyclohexane.

TMEM106B Knockdown Exhibits a Neuroprotective Effect in Parkinson's Disease via Decreasing Inflammation and Iron Deposition.

Parkinson's disease (PD) is closely related to iron accumulation and inflammation. Emerging evidence indicates that TMEM106B plays an essential role in PD. But whether TMEM106B could act on neuroinflammation and iron metabolism in PD has not yet been investigated. The aim of this study was to investigate the pathological mechanisms of inflammation and iron metabolism of TMEM106B in PD. 1-methyl-4-phenylpyridinium (MPP+)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced SH-SY5Y cells and mice were treated with LV-shTMEM106B and AAV-shTMEM106B to construct PD cellular and mouse models. Pole tests and open-field test (OFT) were performed to evaluate the locomotion of the mice. Immunohistochemistry and iron staining were used to detect TH expression and iron deposition in the SN. Iron staining was used to measure the levels of iron. Western blotting was used to detect the expression of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)), NOD-like receptor protein 3 (NLRP3) inflammasome, divalent metal transporter 1 (DMT1), and Ferroportin1 (FPN1)). Knockdown of TMEM106B improved motor ability and rescued dopaminergic (DA) neuron loss. TMEM106B knockdown attenuated the increases of TNF-α, IL-6, NLRP3 inflammasome, and DMT1 expression in the MPP+ and MPTP-induced PD models. Furthermore, TMEM106B knockdown also increases the expression of FPN1. This study provides the first evidence that knockdown of TMEM106B prevents dopaminergic neurodegeneration by modulating neuroinflammation and iron metabolism.

Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway.

Adverse cardiac mechanical remodeling is critical for the progression of heart failure following myocardial infarction (MI). We previously demonstrated the involvement of RIP3-mediated necroptosis in the loss of functional cardiomyocytes and cardiac dysfunction post-MI. Herein, we investigated the role of RIP3 in NOD-like receptor protein 3 (NLRP3)-mediated inflammation and evaluated the effects of RIP3 knockdown on myocardial mechanics and functional changes after MI. Our findings revealed that mice with MI for 4 weeks exhibited impaired left ventricular (LV) myocardial mechanics, as evidenced by a significant decrease in strain and strain rate in each segment of the LV wall during both systole and diastole. However, RIP3 knockdown ameliorated cardiac dysfunction by improving LV myocardial mechanics not only in the anterior wall but also in other remote nonischemic segments of the LV wall. Mechanistically, knockdown of RIP3 effectively inhibited the activation of the nuclear factor kappa-B (NF-κB)/NLRP3 pathway, reduced the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the heart tissues, and mitigated adverse cardiac remodeling following MI. These results suggest that downregulation of RIP3 holds promise for preventing myocardial inflammation and cardiac mechanical remodeling following MI by regulating the NF-κB/NLRP3 pathway.

Advances in and Perspectives on Transgenic Technology and CRISPR-Cas9 Gene Editing in Broccoli.

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in broccoli, and transgenic transformation and CRISPR-Cas9 gene editing techniques have been applied to improve broccoli quality, postharvest shelf life, glucoraphanin accumulation, and disease and stress resistance, among other factors. The construction and application of genetic transformation technology systems have led to rapid development in broccoli worldwide, which is also good for functional gene identification of some potential traits in broccoli. This review comprehensively summarizes the progress in transgenic technology and CRISPR-Cas9 gene editing for broccoli over the past four decades. Moreover, it explores the potential for future integration of digital and smart technologies into genetic transformation processes, thus demonstrating the promise of even more sophisticated and targeted crop improvements. As the field continues to evolve, these innovations are expected to play a pivotal role in the sustainable production of broccoli and the enhancement of its nutritional and health benefits.

CCL17 and CCL19 are markers of disease progression in alveolar echinococcosis.

OBJECTIVES: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality. METHODS: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses. RESULTS: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80. CONCLUSION: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells.

The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.

DNAzyme-activated CRISPR/Cas assay for sensitive and one-pot detection of lead contamination.

Hazardous lead ions (Pb2+) even at a minute level can pose side effects on human health, highlighting the need for tools for trace Pb2+ detection. Herein, we present a DNAzyme-activated CRISPR assay (termed DzCas12T) for sensitive and one-pot detection of lead contamination. Using an extension-bridged strategy eliminates the need for separation to couple the DNAzyme recognition and CRISPR reporting processes. The tandem design endowed the DzCas12T assay with high specificity and sensitivity down to the pM-level. This assay has been used to detect lead contamination in food and water samples, indicating the potential for monitoring lead-associated environmental and food safety.

Successful Treatment of Cutaneous Protothecosis Due to Prototheca wickerhamii with Terbinafine.

Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.

Preparation of a novel antibacterial magnesium carbonate coating on a titanium surface and its in vitro biocompatibility.

Magnesium-based coatings have attracted great attention in surface modification of titanium implants due to their superior angiogenic and osteogenic properties. However, their biological effects as a carbonate-based constituent remain unrevealed. In this study, magnesium carbonate coatings were prepared on titanium surfaces under hydrothermal conditions and subsequently treated with hydrogen peroxide. Also, their antibacterial activity and in vitro cell biocompatibility were evaluated. The obtained coatings consisted of nanoparticles without cracks and exhibited excellent adhesion to the substrate. X-ray diffraction (XRD) results indicated pure magnesium carbonate coatings formed on the Ti surface after hydrothermal treatment. After hydrogen peroxide treatment, the phase composition of the coatings had no obvious change. Compared to the untreated coatings, the hydrogen peroxide-treated coatings showed increased surface roughness and hydrophilicity. Co-culture with Staphylococcus aureus (S. aureus) demonstrated that the obtained coatings had good antibacterial activity. In vitro cell culture results showed that the hydrogen peroxide-treated coatings enhanced the viability, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These findings suggest that this MgCO3-based coating exhibits excellent antibacterial performance and osteogenic potential. Based on the above, this study provides a simple method for preparing titanium implants with dual antibacterial and osteogenic capabilities, holding great promise in clinical applications.

Adipose-derived stem cells can alleviate RHDV2 induced acute liver injury in rabbits.

Rabbit hemorrhagic disease virus (RHDV) can cause fatal fulminant hepatitis, which is very similar to human acute liver failure. The aim of this study was to investigate whether adipose-derived stem cells (ADSCs) could alleviate RHDV2-induced liver injury in rabbits. Twenty 50-day-old rabbits were divided randomly into two groups (RHDV2 group, ADSCs + RHDV2 group). Starting from the 1st day, two groups of rabbits were given 0.5 ml of viral suspensions by subcutaneous injection in the neck. Meanwhile, the ADSCs + RHDV2 group was injected with ADSCs cell suspension (1.5 × 107 cells/ml) via a marginal ear vein, and the RHDV2 group was injected with an equal amount of saline via a marginal ear vein. At the end of the 48 h experiment, the animals were euthanized and gross hepatic changes were observed before liver specimens were collected. Histopathological analysis was performed using hematoxylin-eosin (HE), periodic acid schiff (PAS) and Masson's trichrome staining. For RHDV2 affected rabbits, HE staining demonstrated disorganized hepatic cords, loss of cellular detail, and severe cytoplasmic vacuolation within hepatocytes. Glycogen was not observed with PAS staining, and Masson's Trichrome staining showed increased hepatic collagen deposition. For rabbits treated with ADSCs at the time of inoculation, hepatic pathological changes were significantly less severe, liver glycogen synthesis was increased, and collagen fiber deposition was decreased. For RHDV2 affected rabbits, Tunel and immunofluorescence staining showed that the number of apoptotic cells, TGF-ß, and MMP-9 protein expression increased. And that in the ADSC treated group there was less hepatocyte apoptosis. In addition, RHDV2 induces liver inflammation and promotes the expression of IL-1ß, IL-6, and TNF-α. In rabbits administered ADSCs at time of inoculation, the expression of inflammatory factors in liver tissue decreased significantly. Our experiments show that ADSCs can protect rabbits from liver injury by RHDV2 and reduce the pathological and inflammatory response of liver. However, the specific protective mechanism needs further study.

Added Clinical Value of Intraplaque Neovascularization Detection to Color Doppler Ultrasound for Assessing Ischemic Stroke Risk.

Purpose: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification. Patients and Methods: We recruited 360 patients with ≥50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer-Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test. Results: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666-0.768) and a Hosmer-Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138-0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029-0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617-0.723) increased the C-statistics (p=0.028). Conclusion: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥50% carotid stenosis.

We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk.

One-step creation of CMS lines using a BoCENH3-based haploid induction system in Brassica crop.

Heterosis utilization in a large proportion of crops depends on the use of cytoplasmic male sterility (CMS) tools, requiring the development of homozygous fertile lines and CMS lines1. Although doubled haploid (DH) technology has been developed for several crops to rapidly generate fertile lines2,3, CMS lines are generally created by multiple rounds of backcrossing, which is time consuming and expensive4. Here we describe a method for generating both homozygous fertile and CMS lines through in vivo paternal haploid induction (HI). We generated in-frame deletion and restored frameshift mutants of BoCENH3 in Brassica oleracea using the CRISPR/Cas9 system. The mutants induced paternal haploids by outcrossing. We subsequently generated HI lines with CMS cytoplasm, which enabled the generation of homozygous CMS lines in one step. The BoCENH3-based HI system provides a new DH technology to accelerate breeding in Brassica and other crops.

Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an advanced and noninvasive technology that uses pulse stimulation to treat cognitive impairment. However, its specific effects have always been mixed with those of cognitive training, and the optimal parameter for Alzheimer's disease (AD) intervention is still ambiguous. Objective: This study aimed to summarize the therapeutic effects of pure rTMS on AD, excluding the influence of cognitive training, and to develop a preliminary rTMS treatment plan. Methods: Between 1 January 2010 and 28 February 2023, we screened randomized controlled clinical trials from five databases (PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials. gov). We conducted a meta-analysis and systematic review of treatment outcomes and rTMS treatment parameters. Result: A total of 4,606 articles were retrieved. After applying the inclusion and exclusion criteria, 16 articles, comprising 655 participants (308 males and 337 females), were included in the final analysis. The findings revealed that rTMS significantly enhances both global cognitive ability (p = 0.0002, SMD = 0.43, 95% CI = 0.20-0.66) and memory (p = 0.009, SMD = 0.37, 95% CI = 0.09-0.65). Based on follow-up periods of at least 6 weeks, the following stimulation protocols have demonstrated efficacy for AD: stimulation sites (single or multiple targets), frequency (20 Hz), stimulation time (1-2 s), interval (20-30 s), single pulses (≤2500), total pulses (>20000), duration (≥3 weeks), and sessions (≥20). Conclusions: This study suggests that rTMS may be an effective treatment option for patients with AD, and its potential therapeutic capabilities should be further developed in the future.

Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1.

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.