Screening the Efficacy and Safety of Molluscicides from Three Leaf Extracts of Chimonanthus against the Invasive Apple Snail, Pomacea canaliculata.

Pomacea canaliculata, the invasive snail, is a host of the parasitic nematode Angiostrongylus cantonensis, which has adverse effects on the agriculture system and human health. This work evaluated the molluscicidal activity of petroleum ether extracts (PEEs) from three species of Chimonanthus against the snail P. canaliculate. Pcp (PEE of C. praecox) showed the most effective molluscicide activity. Sixty-one compounds were identified by GC-MS and the main components were terpenoids and fatty acids. The half-lethal concentration (LC50) of Pcp at 24 h (0.27 mg/mL) and 48 h (0.19 mg/mL) was used to evaluate the biochemical alterations in snail tissue. These sublethal concentrations caused the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity to increase, while acetylcholinesterase (AChE) activity decreased. Also, under LC50 treatment, several histological changes were observed in the hepatopancreas and foot of the snail compared with the control group. Moreover, the toxic test in rice demonstrated that Pcp has low toxicity. These results suggest that Pcp could be developed as an effective molluscicide for P. canaliculata control.

Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming.

The nucleotide-binding and oligomerization domain, leucine-rich repeats, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC-0160 or pioglitazone, increased NLRP3 inflammasome activation and IL-1ß secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP-associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC-itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU-induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3-related autoinflammatory diseases.

Association of triglyceride glucose index with all-cause and cardiovascular mortality in the general population.

OBJECTIVE: The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and heart failure. In recent years, much emphasis has been placed on the relationship between the TyG index and mortality in the general population. However, the impact of age on the association between TyG and all-cause and cardiovascular mortality remains controversial. This study investigated the link between the TyG index and all-cause and cardiovascular mortality, emphasizing differences between older and non-older populations. METHODS: Data from the National Health and Nutrition Examination Survey (2009-2018), encompassing 20,194 participants, were analyzed. The baseline TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend tests were employed to explore the association between the TyG index and all-cause and cardiovascular mortality, with emphasis on age-specific analysis. Subgroup analysis was conducted to examine whether the TyG index's association with mortality varied across different subgroups. Additionally, receiver operating characteristic curves were used to compare the predictive ability of the TyG index with the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. RESULTS: Over a median follow-up period of 105 months, all-cause mortality accounted for 13.345% of cases, and cardiovascular mortality accounted for 3.387%. Kaplan-Meier curves showed a significant increase in all-cause and cardiovascular mortality with higher TyG index values (both P for log-rank test < 0.001). However, during Cox proportional hazards regression analysis, no linear trend was observed between the TyG index and all-cause or cardiovascular mortality after adjusting for confounding factors (all-cause mortality: P for trend = 0.424; cardiovascular mortality: P for trend = 0.481). Restricted cubic splines revealed a non-linear association between the baseline TyG index and all-cause and cardiovascular mortality in the overall population (all-cause mortality: Non-linear P = 0.003; cardiovascular mortality: Non-linear P = 0.034). The effect of the TyG index was consistent across most subgroups in terms of all-cause and cardiovascular mortality, with no significant interaction with randomized factors (all-cause mortality: P for interaction = 0.077-0.940, cardiovascular mortality: P for interaction = 0.173-0.987), except for the age subgroup (all-cause mortality: P for interaction < 0.001, cardiovascular mortality: P for interaction < 0.001). Further age-specific analysis revealed that the association between the TyG index and all-cause and cardiovascular mortality remained significant in patients aged < 65 but not in those aged ≥ 65. Interestingly, a non-linear association was observed between the TyG index and all-cause mortality in individuals aged < 65 (Non-linear P = 0.011), while a linear relationship was observed with cardiovascular mortality, showing an upward trend (Non-linear P = 0.742, P for trend = 0.010). Further stratification according to age yielded similar results only in patients aged 45-64 (all-cause mortality: Non-linear P = 0.001 and cardiovascular mortality: Non-linear P = 0.902, P for trend = 0.015). Compared to HOMA-IR, the TyG index demonstrated superior predictive performance for all-cause and cardiovascular mortality (all-cause mortality: 0.620 vs. 0.524, P < 0.001; cardiovascular mortality: 0.623 vs. 0.537, P < 0.001). CONCLUSIONS: This study established a significant association between the TyG index and all-cause and cardiovascular mortality in the general population, particularly among individuals aged < 65. Notably, a non-linear association with all-cause mortality was observed in those aged < 65, while a linear relationship with cardiovascular mortality was found.

Nature-Inspired Surface Structures Design for Antimicrobial Applications.

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation.

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.

Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo.

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

Lappaol F, an anticancer agent, inhibits YAP via transcriptional and post-translational regulation.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. OBJECTIVE: The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. MATERIALS AND METHODS: Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. RESULTS: LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 µmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. CONCLUSION: LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels.

Intra-specific comparison of mitochondrial genomes reveals host gene fragment exchange via intron mobility in Tremella fuciformis.

BACKGROUND: Mitochondrial genomic sequences are known to be variable. Comparative analyses of mitochondrial genomes can reveal the nature and extent of their variation. RESULTS: Draft mitochondrial genomes of 16 Tremella fuciformis isolates (TF01-TF16) were assembled from Illumina and PacBio sequencing data. Mitochondrial DNA contigs were extracted and assembled into complete circular molecules, ranging from 35,104 bp to 49,044 bp in size. All mtDNAs contained the same set of 41 conserved genes with identical gene order. Comparative analyses revealed that introns and intergenic regions were variable, whereas genic regions (including coding sequences, tRNA, and rRNA genes) were conserved. Among 24 introns detected, 11 were in protein-coding genes, 3 in tRNA genes, and the other 10 in rRNA genes. In addition, two mobile fragments were found in intergenic regions. Interestingly, six introns containing N-terminal duplication of the host genes were found in five conserved protein-coding gene sequences. Comparison of genes with and without these introns gave rise to the following proposed model: gene fragment exchange with other species can occur via gain or loss of introns with N-terminal duplication of the host genes. CONCLUSIONS: Our findings suggest a novel mechanism of fungal mitochondrial gene evolution: partial foreign gene replacement though intron mobility.

Formation of hydroperoxo (-OOH) species on the surface of self-doped Bi2.15WO6: reactivity towards As(iii) oxidation.

Bi2+xWO6 is a cost-effective and environmentally friendly photocatalyst that shows high reactivity in the oxidation of various contaminants under visible light. However, under alkaline conditions, the reactive oxidative species in the Bi2+xWO6 system are still not clear yet. In this study, it is observed that the oxidation rates of As(iii) increase with increasing pH values in the Bi2.15WO6 system. Photoluminescence and the Mott-Schottky analyses confirm that OH- promotes the separation and transfer of photogenerated electron-hole pairs over Bi2.15WO6, thus facilitating the oxidation of As(iii). Electron spin resonance spectra analysis and quenching experiments rule out contributions of •OH, O2˙-, 1O2 and superoxo species to As(iii) oxidation and indicate that surface -OOH and/or H2O2 are indeed the predominant species under alkaline conditions. The improved production of H2O2 by H-donors such as glucose and phenol, as well as the UV-vis diffuse reflectance and Raman analyses, further confirms the formation of surface -OOH on Bi2.15WO6 under alkaline conditions. In the dark, the significant higher oxidation rate of As(iii) by H2O2-Bi2.15WO6 than that by H2O2 alone reveals that surface -OOH, instead of H2O2, plays an important role in As(iii) oxidation. This study enriches our understanding of the diversity of reactive oxygen species (ROS) in the Bi2.15WO6 system and gives new insight into the mechanism involved in the oxidation of As(iii) under alkaline conditions.

Effects of prebiotic consumption on serum intestinal fatty acid-binding protein levels in patients with diabetes: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a condition involving several molecular mechanisms related to the intestinal microbiota for its development. Intestinal fatty acid-binding protein (I-FABP) is a sensitive marker to study enterocyte damage. A prebiotic is a non-digestible food ingredient that improves host health by selectively stimulating the growth and/or activities of bacteria in the colon. We aimed to clarify the currently described effects of prebiotics in the prevention and management of T2DM. METHODS: In this case-control study, we chose 68 participants with T2DM and 52 healthy participants. Both groups were further divided based on consumption of prebiotics. Forty participants with T2DM consumed prebiotics, and 28 did not; 30 healthy volunteers consumed prebiotics, and 22 did not. We used the analysis of variance to compare the inflammation levels between the case and control groups. Multiple linear regression was performed for the significantly correlated groups to estimate the influence of prebiotics on inflammation level. RESULTS: Age was a significant factor for difference in I-FABP levels (standardized coefficient: 0.06; P = .047). The analysis of eating habits showed that vegetarian diets produced lower I-FABP levels than non-vegetarian diets (standardized coefficient: -2.55; P = .022). Results showed that patients with T2DM who consumed prebiotics expressed lower I-FABP levels, reflecting an improvement in inflammation level, than the healthy volunteers who did not consume prebiotics (standardized coefficient: -3.20; P = .019). CONCLUSIONS: For patients with T2DM, prebiotics supplemented produced no significant impact on serum I-FABP levels.

A Review of SARS-CoV-2 and the Ongoing Clinical Trials.

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization.

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch's membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy.

P3HT:Bebq2-Based Photovoltaic Device Enhances Differentiation of hiPSC-Derived Retinal Ganglion Cells.

Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.

Intraoperative Mapping of the Subfascial Plexus Using the Transillumination Method for Head and Neck Reconstruction with Free Style Anterolateral Thigh Flaps.

Without well recognizing the vascular territories of the perforator, surgery might damage the pedicle and diminish flap survival. This study described a transillumination method for intraoperative mapping of the subfascial plexus of the perforator in the head and neck reconstruction with an anterolateral thigh (ALT) flap and also compared the perioperative outcomes and complications of the method with those of the conventional two-pedicle ALT flap. Between January 2011 and December 2017, 26 patients who underwent head and neck reconstruction with ALT flaps were evaluated as follows: 13 underwent the transillumination method (case group), and 13 (age- and sex-matched) underwent standard two-pedicle flap procedures (control group). Demographic factors, diagnosis, flap size, recipient site, perioperative data, and postoperative complications were compared between the two groups. There was no significant difference in age, sex, diagnosis, recipient sites, and flap size between the case and control groups. Regarding the perioperative outcomes, the harvesting time was significantly shorter in the case group than in the control group (60 vs. 100 minutes, p < 0.001). The operative time was shorter in the case group than in the control group, but this difference was not statistically significant (300 vs. 420 minutes, p = 0.058). The transillumination method can allow plastic surgeons to easily identify the perforator vascular plexus of the ALT flap, which facilitates intraoperative flap design in head and neck reconstruction.

Development of a Graphene Oxide-Incorporated Polydimethylsiloxane Membrane with Hexagonal Micropillars.

Several efforts have been made on the development of bioscaffolds including the polydimethylsiloxane (PDMS) elastomer for supporting cell growth into stable sheets. However, PDMS has several disadvantages, such as intrinsic surface hydrophobicity and mechanical strength. Herein, we generated a novel PDMS-based biomimetic membrane by sequential modifications of the PMDS elastomer with graphene oxide (GO) and addition of a hexagonal micropillar structure at the bottom of the biomembrane. GO was initially homogenously mixed with pure PDMS and then was further coated onto the upper surface of the resultant PDMS. The elastic modulus and hydrophilicity were significantly improved by such modifications. In addition, the development of hexagonal micropillars with smaller diameters largely improved the ion permeability and increased the motion resistance. We further cultured retinal pigment epithelial (RPE) cells on the surface of this modified PDMS biomembrane and assayed its biocompatibility. Remarkably, the GO incorporation and coating exhibited beneficial effect on the cell growth and the new formation of tight junctions in RPE cells. Taken together, this GO-modified PDMS scaffold with polyhexagonal micropillars may be utilized as an ideal cell sheet and adaptor for cell cultivation and can be used in vivo for the transplantation of cells such as RPE cells.

Analysis of the Mitochondrial Genome in Hypomyces aurantius Reveals a Novel Twintron Complex in Fungi.

Hypomyces aurantius is a mycoparasite that causes cobweb disease, a most serious disease of cultivated mushrooms. Intra-species identification is vital for disease control, however the lack of genomic data makes development of molecular markers challenging. Small size, high copy number, and high mutation rate of fungal mitochondrial genome makes it a good candidate for intra and inter species differentiation. In this study, the mitochondrial genome of H. H.a0001 was determined from genomic DNA using Illumina sequencing. The roughly 72 kb genome shows all major features found in other Hypocreales: 14 common protein genes, large and small subunit rRNAs genes and 27 tRNAs genes. Gene arrangement comparison showed conserved gene orders in Hypocreales mitochondria are relatively conserved, with the exception of Acremonium chrysogenum and Acremonium implicatum. Mitochondrial genome comparison also revealed that intron length primarily contributes to mitogenome size variation. Seventeen introns were detected in six conserved genes: five in cox1, four in rnl, three in cob, two each in atp6 and cox3, and one in cox2. Four introns were found to contain two introns or open reading frames: cox3-i2 is a twintron containing two group IA type introns; cox2-i1 is a group IB intron encoding two homing endonucleases; and cox1-i4 and cox1-i3 both contain two open reading frame (ORFs). Analyses combining secondary intronic structures, insertion sites, and similarities of homing endonuclease genes reveal two group IA introns arranged side by side within cox3-i2. Mitochondrial data for H. aurantius provides the basis for further studies relating to population genetics and species identification.

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages.

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

Application and value of anxiety and depression scale in patients with functional dyspepsia.

BACKGROUND: Patients with functional dyspepsia (FD) cannot be assessed for their mental health using a suitable and practical measure. The purpose of the study is to investigate the usefulness of several anxiety and depression scales in patients with FD, offering recommendations for clinical identification and therapy. METHODS: From September 2021 to September 2022, patients were sought and selected. The psychological symptoms were assessed using ten depression or anxiety questionnaires. The receiver operating characteristic (ROC) curve, Spearman analysis, Pearson correlation analysis, and single factor analysis were applied. RESULTS: Prospective analysis was performed on 142 healthy individuals and 113 patients with FD. In the case group, anxiety and depression symptoms were more common than in the control group, and the 10 scales showed strong validity and reliability. HAMD had the strongest connection with the PHQ-9 score on the depression scale (0.83). The score correlation between SAS and HAMA on the anxiety analysis scale was the greatest at 0.77. The PHQ-9, SAS, HAMD, and HAMA measures performed exceptionally well in detecting FD with anxiety or depression symptoms (AUC = 0.72, 0.70, 0.70, 0.77, and 0.77, respectively). CONCLUSIONS: PHQ-9, SAS, HAMD, and HAMA scales have good application performance in FD patients. They can assist gastroenterologists in evaluating anxiety and depression symptoms, and provide reference and guidance for subsequent treatment.

Leber's hereditary optic neuropathy: Update on the novel genes and therapeutic options.

A maternal inheritance disorder called Leber's hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3 , YARS2 , and DNAJC30 , which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria . DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.