A rare complex structural variant of novel intragenic inversion combined with reciprocal translocation t(X;1)(p21.2;p13.3) in Duchenne muscular dystrophy.

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

Crohn's disease treatment and memory T-cell subset changes: insights from a case series.

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.

Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity.

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 µM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 µM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.

Development of a brief bedside tool to screen women sexual assault survivors for risk of persistent posttraumatic stress six months after sexual assault.

This study aims to develop and validate a brief bedside tool to screen women survivors presenting for emergency care following sexual assault for risk of persistent elevated posttraumatic stress symptoms (PTSS) six months after assault. Participants were 547 cisgender women sexual assault survivors who presented to one of 13 sexual assault nurse examiner (SANE) programs for medical care within 72 h of a sexual assault and completed surveys one week and six months after the assault. Data on 222 potential predictors from the SANE visit and the week one survey spanning seven broadly-defined risk factor domains were candidates for inclusion in the screening tool. Elevated PTSS six months after assault were defined as PCL-5 > 38. LASSO logistic regression was applied to 20 randomly selected bootstrapped samples to evaluate variable importance. Logistic regression models comprised of the top 10, 20, and 30 candidate predictors were tested in 10 cross-validation samples drawn from 80% of the sample. The resulting instrument was validated in the remaining 20% of the sample. AUC of the finalized eight-item prediction tool was 0.77 and the Brier Score was 0.19. A raw score of 41 on the screener corresponds to a 70% risk of elevated PTSS at 6 months. Similar performance was observed for elevated PTSS at one year. This brief, eight-item risk stratification tool consists of easy-to-collect information and, if validated, may be useful for clinical trial enrichment and/or patient screening.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

Study on the Damage of Fiber-Reinforced Seawater Sea Sand Concrete by Freezing and Thawing of Seawater.

The use of seawater and sea sand as replacements for fresh water and river sand in the preparation of seawater and sea sand concrete can effectively address issues such as high transportation costs, extended construction periods, and resource wastage. Nevertheless, in northern coastal areas, the problem of concrete durability in the complex and changing marine environment is more prominent. Research on the durability of seawater sea sand concrete is beneficial to the widening of its application range. To investigate the impact of glass fiber (GF) and polyvinyl alcohol fiber (PVA) with different blending methods on the seawater freeze-thaw resistance of seawater sea sand concrete (SSC), corresponding specimens were prepared, and seawater freeze-thaw cycling tests were conducted. By adopting the slow-freezing method and combining macro-structure and micro-morphology, the damage mechanism and the deterioration law of fiber-reinforced SSC under seawater freezing and thawing were investigated. The results indicate that, macroscopically, the incorporation of GF and PVA can effectively mitigate the damage to the matrix and reduce the effects of external erosive substances on the rate of strength loss, the rate of mass loss, and the relative dynamic elastic modulus. After 75 cycles, the SSC with a total volume doping of 0.3% and a blending ratio of 1:1 showed a 41.23% and 27.55% reduction in mass loss and strength loss, respectively, and a 29.9% improvement in relative dynamic elastic modulus compared with the basic group. Microscopic analysis reveals that the combined effect of freezing and expansion forces, the expansive substances generated by seawater intrusion into the interior of the matrix, and salt crystallization all weaken the bond between aggregate and mortar, leading to accelerated deterioration of the concrete. The incorporation of fibers enables the matrix to become denser and improves its crack-resistant properties, resulting in a better durability than that of the basic group. The damage prediction model established by the NSGM(1,N) model of gray system theory exhibits high accuracy and is suitable for long-term prediction, accurately predicting the damage of seawater sea sand concrete under seawater freeze-thaw coupling.

Study on the Bonding Performance of BFRP Bars with Seawater Sand Concrete.

A total of 66 sets of pullout specimens were prepared to investigate the bonding properties of basalt fiber-reinforced polymer reinforcement (hereinafter referred to as BFRP) with seawater sand concrete (hereinafter referred to as SSC). The volume dosages of mono-doped glass fibers and mono-doped polypropylene fibers were 0.1%, 0.2%, and 0.3%; the total volume dosage was set to be constant at 0.3%; and the doping ratios of the hybrid fibers were 1:2, 1:1, and 2:1. The effect on the bonding performance of BFRP reinforcement with SSC was studied on the condition of the diameter D of the BFRP reinforcement being 12 mm; the bond length of SSC being 3D, 5D, and 7D; and the surface characteristics of the reinforcement being sandblasted and threaded. The research showed that due to internal cracks in the matrix, salt crystals in the pores, chloride salts with high brittleness and expansion, as well as sulfate corrosion products such as "Frederick salts" in SSC, the concrete became brittle, resulting in more brittle splitting failures during the pullout test. Doped fibers can increase the ductility effect of concrete, but the bonding effect between the threaded fiber reinforcement and the SSC was not as good as that of the sandblasting group. When the bond length was 5D, the bonding effect between the BFRP reinforcement and SSC was the best, and the bonding performance of the experimental group with doped fibers was better than that of the threaded group. Finally, by combining the ascending segment of the Malvar model with the descending segment of the improved BPE model, a constitutive relationship model suitable for the bond-slip curve between BFRP reinforcement and SSC was fitted, which laid a theoretical foundation for future research on SSC.

Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 -/- mice.

Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.

Th2-skewed peripheral T helper cells drives B cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. However, the involvement of T cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. Th1, Th2, Th17, Treg and IL-21+CD4+T cells in total or sorted subsets of peripheral blood mononuclear cells (PBMCs) and ABPA Bronchoalveolar Lavage fluid (BALF) were analyzed by flow cytometry. RNA sequencing of subsets of CD4+T cells were done in exacerbated ABPA patients and healthy controls. Antibodies of T-B cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T cells was rarely detected in healthy controls but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T cells were mainly peripheral T helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T helper (Tfh) cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

From antioxidant defense to genotoxicity: Deciphering the tissue-specific impact of AgNPs on marine clam Ruditapes philippinarum.

The escalating use of silver nanoparticles (AgNPs) across various sectors for their broad-spectrum antimicrobial capabilities, has raised concern over their potential ecotoxicological effects on aquatic life. This study explores the impact of AgNPs (50 µg/L) on the marine clam Ruditapes philippinarum, with a particular focus on its gills and digestive glands. We adopted an integrated approach that combined in vivo exposure, biochemical assays, and transcriptomic analysis to evaluate the toxicity of AgNPs. The results revealed substantial accumulation of AgNPs in the gills and digestive glands of R. philippinarum, resulting in oxidative stress and DNA damage, with the gills showing more severe oxidative damage. Transcriptomic analysis further highlights an adaptive up-regulation of peroxisome-related genes in the gills responding to AgNP-induxed oxidative stress. Additionally, there was a noteworthy enrichment of differentially expressed genes (DEGs) in key biological processes, including ion binding, NF-kappa B signaling and cytochrome P450-mediated metabolism of xenobiotics. These insights elucidate the toxicological mechanisms of AgNPs to R. philippinarum, emphasizing the gill as a potential sensitive organ for monitoring emerging nanopollutants. Overall, this study significantly advances our understanding of the mechanisms driving nanoparticle-induced stress responses in bivalves and lays the groundwork for future investigations into preventing and treating such pollutants in aquaculture.

A comprehensive sampling of mitogenomes shows the utility to infer phylogeny of termites (Blattodea: Termitoidae).

The mitogenome sequence data have been widely used in inferring the phylogeny of insects. In this study, we determined the complete mitogenome for Macrotermes sp. (Termitidae, Macrotermitinae) using next-generation sequencing. Macrotermes sp. possesses a typical insect mitogenome, displaying an identical gene order and gene content to other existing termite mitogenomes. We present the first prediction of the secondary structure of ribosomal RNA genes in termites. The rRNA secondary structures of Macrotermes sp. exhibit similarities to closely related insects and also feature distinctive characteristics in their helical structures. Together with 321 published mitogenomes of termites as ingroups and 8 cockroach mitogenomes as outgroups, we compiled the most comprehensive mitogenome sequence matrix for Termitoidae to date. Phylogenetic analyses were conducted using datasets employing different data coding strategies and various inference methods. Robust relationships were recovered at the family or subfamily level, demonstrating the utility of comprehensive mitogenome sampling in resolving termite phylogenies. The results supported the monophyly of Termitoidae, and consistent relationships within this group were observed across different analyses. Mastotermitidae was consistently recovered as the sister group to all other termite families. The families Hodotermitidae, Stolotermitidae, and Archotermopsidae formed the second diverging clade, followed by the Kalotermitidae. The Neoisoptera was consistently supported with strong node support, with Stylotermitidae being sister to the remaining families. Rhinotermitidae was found to be non-monophyletic, and Serritermitidae nested within the basal clades of Rhinotermitidae and was sister to Psammotermitinae. Overall, our phylogenetic results are largely consistent with earlier mitogenome studies.

Research on dynamic characteristics of cutter breaking frozen soil and optimal drum rotation speed of the new shaft tunneling machine.

To improve the efficiency of frozen soil excavation, the new shaft tunneling machine was developed. The new shaft tunneling machine exerts pressure on the frozen soil through the cutter under the joint action of its own gravity, the drum rotational force and the inertia force, and the frozen soil is damaged. By unique way of breaking frozen soil to improve the efficiency of frozen soil excavation, the drum rotation speed is one of the factors affecting the performance of frozen soil excavation. This article applies SolidWorks software to establish the model of cutter breaking frozen soil, takes advantage of Hyper Mesh finite element software coupled with LS-DYNA solver to acquire the regular pattern of change in the force change, frozen soil stress-strain and specific energy of cutter crushing frozen soil, etc., which analyzes the destruction of frozen soil when the drum of the new shaft tunneling machine is rotating at the speed of 25-40 rpm. Combine with field test to investigate the mechanism of cutter breaking frozen soil under the optimal drum rotation speed. The investigation results demonstrate that: when frozen soil's self-bearing capacity is lower than the force of cutter, it breaks up and detaches from the soil body, and frozen soil undergoes tensile, compressive and shear damages. For this research, it is instructive for practical engineering.

The Emotion Regulation of Acupuncture in Chronic Low Back Pain: A Clinical Neuroimaging Protocol.

Introduction: Acupuncture is effective for patients with chronic low back pain (CLBP), which can relieve pain intensity and regulate negative emotional states such as pain-related anxiety and depression. Previous studies mainly discuss the analgesic mechanism of acupuncture treatment of CLBP, but there are multiple dimensions to pain, including sensation, emotion and cognition. Therefore, this study aims to investigate the central mechanism of acupuncture for CLBP from the perspective of emotional regulation by functional magnetic resonance imaging (fMRI). Methods and Analysis: A total of 72 patients with CLBP will be recruited in the study and randomly assigned to the verum acupuncture group or the sham acupuncture group. The trail will last for 18 weeks including a 2-week baseline, a 4-week treatment and a 12-week for follow-up period. The primary outcomes are the visual analog scale (VAS) and the Japanese Orthopaedic Association Scores (JOA) score. The secondary outcomes are the 12-item short form health survey (SF-12), the state trait anxiety inventory (STAI), the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The VAS, JOA, STAI SAS and SDS will be collected at baseline, week 2, week 4, and after follow-up. The SF-12 will be evaluated at baseline, week 2 and week 4. Functional magnetic resonance imaging (MRI) data will be collected at baseline and the end of treatment. Emotion-related brain regions will be chosen as regions of interest (ROIs). The gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and large-scale functional brain network based on these ROIs will be analyzed within and between the two groups. Discussion: This study will verify the emotional regulation of acupuncture and explore the mechanism of acupuncture for emotion regulation in patients with CLBP. Trial Registration Number: https://www.chictr.org.cn/showproj.html?proj=195486, identifier: ChiCTR2300070557.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

Metformin enhances METTL14-Mediated m6A methylation to alleviate NIT-1 cells apoptosis induced by hydrogen peroxide.

Injuries to pancreatic ß-cells are intricately linked to the onset of diabetes mellitus (DM). Metformin (Met), one of the most widely prescribed medications for diabetes and metabolic disorders, has been extensively studied for its antioxidant, anti-aging, anti-glycation, and hepatoprotective activities. N6-methyladenosine (m6A) plays a crucial role in the regulation of ß-cell growth and development, and its dysregulation is associated with metabolic disorders. This study aimed to elucidate the mechanistic basis of m6A involvement in the protective effects of Met against oxidative damage in pancreatic ß-cells. Hydrogen peroxide (H2O2) was employed to induce ß-cell damage. Remarkably, Met treatment effectively increased methylation levels and the expression of the methyltransferase METTL14, subsequently reducing H2O2-induced apoptosis. Knocking down METTL14 expression using siRNA significantly compromised cell viability. Conversely, targeted overexpression of METTL14 specifically in ß-cells substantially enhanced their capacity to withstand H2O2-induced stress. Molecular evidence suggests that the anti-apoptotic properties of Met may be mediated through Bcl-xL and Bim proteins. In conclusion, our findings indicate that Met induces METTL14-mediated alterations in m6A methylation levels, thereby shielding ß-cells from apoptosis and oxidative damage induced by oxidative stress.

Treatment of Depression with Acupuncture Based on Pathophysiological Mechanism.

Depression is a prevalent mental disorder and has a profound impact on an individual's psychological and physical well-being. It is characterized by a persistently depressed mood, loss of interest, energy loss, and cognitive dysfunction. In recent years, more and more people have changed to mental diseases, such as depression, anxiety, mania and so on. In the incidence of depression, covering all ages, but still mainly young and middle-aged women. Traditional treatments for depression mainly rely on medication and psychotherapy, but these methods are not effective for all patients and are often accompanied by certain side effects. Therefore, finding safe and effective alternative or adjuvant treatments has become a priority. Here we highlight the research progress of acupuncture in the treatment of depression and to explore the mechanism of acupuncture in the treatment of depression. Acupuncture treatment of depression is an ancient and effective method, the mechanism involves multiple biological pathways, for example, by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammatory and other effects, improving emotional state and play an antidepressant role. To provide evidence to support the widespread use of acupuncture in clinical practice. We hope to provide new treatment ideas and methods for patients with depression, and even reduce the incidence of depression.