HervD Atlas: a curated knowledgebase of associations between human endogenous retroviruses and diseases.

Human endogenous retroviruses (HERVs), as remnants of ancient exogenous retrovirus infected and integrated into germ cells, comprise ∼8% of the human genome. These HERVs have been implicated in numerous diseases, and extensive research has been conducted to uncover their specific roles. Despite these efforts, a comprehensive source of HERV-disease association still needs to be added. To address this gap, we introduce the HervD Atlas (https://ngdc.cncb.ac.cn/hervd/), an integrated knowledgebase of HERV-disease associations manually curated from all related published literature. In the current version, HervD Atlas collects 60 726 HERV-disease associations from 254 publications (out of 4692 screened literature), covering 21 790 HERVs (21 049 HERV-Terms and 741 HERV-Elements) belonging to six types, 149 diseases and 610 related/affected genes. Notably, an interactive knowledge graph that systematically integrates all the HERV-disease associations and corresponding affected genes into a comprehensive network provides a powerful tool to uncover and deduce the complex interplay between HERVs and diseases. The HervD Atlas also features a user-friendly web interface that allows efficient browsing, searching, and downloading of all association information, research metadata, and annotation information. Overall, the HervD Atlas is an essential resource for comprehensive, up-to-date knowledge on HERV-disease research, potentially facilitating the development of novel HERV-associated diagnostic and therapeutic strategies.

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis.

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

Free Halogen Substitution of Chiral Hybrid Metal Halides for Activating the Linear and Nonlinear Chiroptical Properties.

Halogen substitution has been proven as an effective approach to the band gap engineering and optoelectronic modulation of organic-inorganic hybrid metal halide (OIHMH) materials. Various high-performance mixed halide OIHMH film materials have been primarily obtained through the substitution of coordinated halogens in their inorganic octahedra. Herein, we propose a new strategy of substitution of free halogen outside the inorganic octahedra for constructing mixed halide OIHMH single crystals with chiral structures, resulting in a boost of their linear and nonlinear chiroptical properties. The substitution from DMA4[InCl6]Cl (DMA = dimethylammonium) to DMA4[InCl6]Br crystals through a facile antisolvent vaporization method produces centimeter-scale single crystals with high thermal stability along with high quantum yield photoluminescence, conspicuous circularly polarized luminescence, and greatly enhanced second harmonic generation (SHG). In particular, the obtained DMA4[InCl6]Br single crystal features an intrinsic chiral structure, exhibiting a significant SHG circular dichroism (SHG-CD) response with a highest reported anisotropy factor (gSHG-CD) of 1.56 among chiral OIHMH materials. The enhancements in both linear and nonlinear chiroptical properties are directly attributed to the modulation of octahedral distortion. The mixed halide OIHMH single crystals obtained by free halogen substitution confine the introduced halogens within free halogen sites of the lattice, thereby ensuring the stability of compositions and properties. The successful employment of such a free halogen substitution approach may broaden the horizon of the regulation of structures and the optoelectronic properties of the OIHMH materials.

Spatial analysis of overweight prevalence in China: exploring the association with air pollution.

BACKGROUND: Overweight is a known risk factor for various chronic diseases and poses a significant threat to middle-aged and elderly adults. Previous studies have reported a strong association between overweight and air pollution. However, the spatial relationship between the two remains unclear due to the confounding effects of spatial heterogeneity. METHODS: We gathered height and weight data from the 2015 China Health and Retirement Long-term Survey (CHARLS), comprising 16,171 middle-aged and elderly individuals. We also collected regional air pollution data. We then analyzed the spatial pattern of overweight prevalence using Moran's I and Getis-Ord Gi* statistics. To quantify the explanatory power of distinct air pollutants for spatial differences in overweight prevalence across Southern and Northern China, as well as across different age groups, we utilized Geodetector's q-statistic. RESULTS: The average prevalence of overweight among middle-aged and elderly individuals in each city was 67.27% and 57.39%, respectively. In general, the q-statistic in southern China was higher than that in northern China. In the north, the prevalence was significantly higher at 54.86% compared to the prevalence of 38.75% in the south. SO2 exhibited a relatively higher q-statistic in middle-aged individuals in both the north and south, while for the elderly in the south, NO2 was the most crucial factor (q = 0.24, p < 0.01). Moreover, fine particulate matter (PM2.5 and PM10) also demonstrated an important effect on overweight. Furthermore, we found that the pairwise interaction between various risk factors improved the explanatory power of the prevalence of overweight, with different effects for different age groups and regions. In northern China, the strongest interaction was found between NO2 and SO2 (q = 0.55) for middle-aged individuals and PM2.5 and SO2 (q = 0.27) for the elderly. Conversely, in southern China, middle-aged individuals demonstrated the strongest interaction between SO2 and PM10 (q = 0.60), while the elderly showed the highest interaction between NO2 and O3 (q = 0.42). CONCLUSION: Significant spatial heterogeneity was observed in the effects of air pollution on overweight. Specifically, air pollution in southern China was found to have a greater impact on overweight than that in northern China. And, the impact of air pollution on middle-aged individuals was more pronounced than on the elderly, with distinct pollutants demonstrating significant variation in their impact. Moreover, we found that SO2 had a greater impact on overweight prevalence among middle-aged individuals, while NO2 had a greater impact on the elderly. Additionally, we identified significant statistically interactions between O3 and other pollutants.

Endophytic Bacterium Lysobacter firmicutimachus Strain 5-7 Is a Promising Biocontrol Agent Against Rice Seedling Disease Caused by Pythium arrhenomanes in Nursery Trays.

Rice root rot disease caused by Pythium spp. is a highly destructive disease in rice nurseries. Biocontrol with endophytic bacteria was developed in this study to control rice seedling diseases. An in planta screening assay revealed that two bacterial endophytes, strains 5-7 and 6-4, displayed strong protection of rice seedlings from attack by Pythium arrhenomanes. Phylogenetic analysis indicated that strain 5-7 is Lysobacter firmicutimachus, while strain 6-4 belongs to the Kitasatospora genus. To quickly evaluate the disease severity of the root system damaged by Pythium spp. in nursery trays, a root surface area measurement assay was developed. By using this measurement, the control efficacy in nursery trays was evaluated, and L. firmicutimachus 5-7 showed promising biocontrol activity against Pythium disease. In a field trial, the two endophytes exhibited significant disease control efficacy on rice brown spot disease caused by Bipolaris oryzae naturally occurring in a commercial nursery field. The two endophytes exhibited multiple enzymatic activities and broad-spectrum antagonistic activities against multiple rice pathogens. The two endophytes colonized the root surface and inside of the root. L. firmicutimachus 5-7 primarily colonized the intercellular space and aerenchyma. Antibiosis is the major mechanism used by strain 5-7 to cause Bipolaris hyphal swelling and inhibit Pythium zoospore germination and sporangium formation, while a hyperparasitism-like phenomenon was found in the interaction of strain 6-4 with Pythium and Bipolaris hyphae. In conclusion, we report the promising biocontrol agent L. firmicutimachus 5-7 and the potential biocontrol agent Kitasatospora sp. 6-4 for disease control of rice seedlings in commercial nursery trays and their possible mechanisms of action.

Modulating the ERK1/2-MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells.

Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA's antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan-Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells' progression through inhibition of the ERK1/2-MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC.

Copper-cobalt dual-site on N-doped carbon nanotube with dual-promoted synergy for glucose electrochemical detection.

Doping specific active sites and accelerating the decisive step of glucose catalysis to construct highly active glucose sensing electrochemical catalysts remains a major challenge for glucose sensing. Herein, we report the detailed design of Cu-Co dual active site N-doped carbon nanotube (CuCo-NCNTs) obtained by electrodeposition modification, programmed warming and calcination for electrochemical glucose detection. In the CuCo-NCNTs material system, Cu serves as the main active site for glucose sensing. Co with good adsorption of hydroxyl groups acts as the site providing hydroxyl groups to provide oxygen source for Cu oxidized glucose sensing. The synergistic effect between the two active sites in the Cu-Co system and the abundant micro-reactive sites exposed by carbon nanotubes greatly ensure the excellent electrocatalytic performance of glucose oxidation reaction. Therefore, CuCo-NCNTs have good electrocatalytic performance with a sensitivity of 0.84 mA mM-1 cm-2 and a detection limit of 1 µM, and also have excellent stability and specificity. DFT calculations elucidate the decisive steps of H-atom removal in the oxidation of glucose by Cu active site N-doped carbon nanotube (Cu-NCNTs) and Co active site N-doped carbon nanotube (CuCo-NCNTs) materials, illustrating the role of oxygen source provided by hydroxyl group adsorption in the electrochemical sensing process of glucose, thus demonstrating that the electrochemical sensing signal of glucose can be effectively enhanced when cobalt species that readily adsorb hydroxyl groups are introduced into the materials.

NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.

Nitrogen permease regulator-like 2 (NPRL2/TUSC4) is known to exert both tumor-suppressing and oncogenic effects in different types of cancers, suggesting that its actions are context dependent. Here, we delineated the molecular and functional effects of NPRL2 in malignantly transformed bronchial epithelial cells. To do so, we depleted NPRL2 in oncogenic HRas-transduced and malignantly transformed human bronchial epithelial (BEAS2B), Ras-AI-T2 cells. Intriguingly, depletion of NPRL2 in these cells induced activation of mTORC1 downstream signaling, inhibited autophagy, and impaired Ras-AI-T2 cell proliferation both in vitro and in vivo. These results suggest that NPRL2 is required for oncogenic HRas-induced cell transformation. Depletion of NPRL2 increased levels of the DNA damage marker γH2AX, the cell cycle inhibitors p21 and p27, and the apoptosis marker cleaved-PARP. These NPRL2-depleted cells first accumulated at G1 and G2, and later exhibited signs of mitotic catastrophe, which implied that NPRL2 depletion may be detrimental to oncogenic HRas-transformed cells. Additionally, NPRL2 depletion reduced heat shock factor 1/heat shock element- and NRF2/antioxidant response element-directed luciferase reporter activities in Ras-AI-T2 cells, indicating that NPRL2 depletion led to the suppression of two key cytoprotective processes in oncogenic HRas-transformed cells. Overall, our data suggest that oncogenic HRas-transduced and malignantly transformed cells may depend on NPRL2 for survival and proliferation, and depletion of NPRL2 also induces a stressed state in these cells.

Comprehensive analysis indicated that NDE1 is a potential biomarker for pan-cancer and promotes bladder cancer progression.

BACKGROUND: The nuclear distribution E homologue 1 (NDE1) is a crucial dynein binding partner. The NDE1 protein has the potential to disrupt the normal functioning of centrosomes, leading to a compromised ability to generate spindles and ensure precise separation of chromosomes during cell division. The potential consequences of this phenomenon include genomic instability, malignant transformation and the proliferation of neoplastic growths. However, studies examining the connection between NDE1 and cancer is still very rare. METHODS: The expression level, prognostic impact, gene change, DNA methylation, protein interaction, mRNA m6A modification, ceRNA network, associated gene and function enrichment, and immune-related effects of NDE1 in pan-cancer were examined using a range of online analytic tools and the R software package. The CCK-8 test, transwell assay, scratch assay and colony formation assay were used to confirm the effects of NDE1 on the proliferation, invasion and metastasis of bladder cancer cells. RESULTS: Numerous tumour types have elevated NDE1, which is linked to a bad prognosis. NDE1 is an excellent diagnostic tool for many different types of cancer. Numerous malignancies have been linked to genetic changes in NDE1. NDE1 was connected to TMB, MSI, several immunological checkpoint genes and immune cell infiltration. NDE1 is linked to a number of immunological subtypes. NDE1 could affect how well immunotherapy works to treat different types of cancer. NDE1 was mostly associated with cell cycle, chromosomal segregation, DNA replication and mitotic segregation, according to GO and KEGG analyses. NDE1 physically binds to PAFAH1B1 and DCTN1, respectively. The proliferation, invasion and metastasis of bladder cancer cells may be prevented by NDE1 knockdown. Furthermore, knockdown of NDE1 promoted the apoptosis of bladder cancer cells. CONCLUSION: High expression of NDE1 is present in a variety of tumours, which is linked to a bad prognosis for cancer. Knockdown of NDE1 inhibited the proliferation, invasion and metastasis of bladder cancer cells, and promoted the apoptosis. For a number of malignancies, NDE1 may be a biomarker for immunotherapy and prognosis.

Exosomes on the development and progression of renal fibrosis.

Renal fibrosis is a prevalent pathological alteration that occurs throughout the progression of primary and secondary renal disorders towards end-stage renal disease. As a complex and irreversible pathophysiological phenomenon, it includes a sequence of intricate regulatory processes at the molecular and cellular levels. Exosomes are a distinct category of extracellular vesicles that play a crucial role in facilitating intercellular communication. Multiple pathways are regulated by exosomes produced by various cell types, including tubular epithelial cells and mesenchymal stem cells, in the context of renal fibrosis. Furthermore, research has shown that exosomes present in bodily fluids, including urine and blood, may be indicators of renal fibrosis. However, the regulatory mechanism of exosomes in renal fibrosis has not been fully elucidated. This article reviewed and analysed the various mechanisms by which exosomes regulate renal fibrosis, which may provide new ideas for further study of the pathophysiological process of renal fibrosis and targeted treatment of renal fibrosis with exosomes.

Distribution of scoliosis in 2.22 million adolescents in mainland China: A population-wide analysis.

Background: The characteristics of scoliosis afflicting school children and adolescents in mainland China are still unclear. Therefore, we conducted a systematic review to estimate scoliosis's prevalence and characterise its distribution in China. Methods: We screened PubMed, Scopus, WanFang, China National Knowledge Infrastructure, National Science and Technology Library, and WeiPu databases for mainland China articles published between 1 January 1980 and 31 October 2022. Among them, we identified population-wide scoliosis studies in school children and adolescents. The main outcomes were the positive rate of primary screening and the prevalence of final screening. Primary screening mainly included general examination with/without the forward bending test in school. The final screening entailed clinical diagnosis by Röntgen radiation in a hospital (based on primary screening). A meta-analysis of scoliosis distribution by gender was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Further, we analysed the distributions of scoliosis by age, region, aetiological type, and severity of curvature, in addition to the correlation between its prevalence and altitude or latitude. Results: 77 studies with 2 224 320 participants were included. The positive rate through primary screening was 3.97%, whereas the prevalence of scoliosis at final screening was 1.20%. Analysing the data revealed a higher prevalence of scoliosis in girls (OR = 1.57; 95% CI = 1.38-1.81). The age-wise peak rate of scoliosis was 15-16 years (1.07%) in boys and 13-14 years (1.42%) in girls. The mean prevalence of scoliosis was 1.07% in the western region, 1.54% in the central, and 1.35% in the eastern. Scoliosis prevalence was not correlated with either altitude or latitude. The prevalence of idiopathic and congenital scoliosis was 1.18 and 0.03%. Among all subjects with scoliosis, 79.10 and 16.80% had mild and medium disease severity. Conclusions: According to this comprehensive study using data sets of scoliosis in adolescents across mainland China, the mean prevalence of scoliosis is 1.20%, yet 1.57 times higher in girls than boys, and is most prevalent in the middle region. Overall, scoliosis in adolescents could pose a burden to public health in mainland China. Registration: PROSPERO CRD42021231987.

Enhanced electrochemical glucose sensing of Co/Cu-MOF by hydroxyl adsorption induced reactive oxygen species.

Exploring the factors affecting the electrochemical catalytic signal of an organic-metal material sensor and analyzing the decisive steps of the glucose oxidation behavior are challenging problems. Here, we designed a copper-cobalt-based organic backbone with excellent sensing properties based on the nanostructure of "ultramicroelectrodes", and explored the role of different hydroxyl adsorption capacities in the sensing process of glucose oxidation. Dimethylimidazole was used as a starting substrate, and then copper and cobalt ions were introduced by hydrothermal treatment to prepare a copper-cobalt-based organic backbone (Co/Cu-MOF) with good electrochemical glucose sensing ability. Due to the abundant micro-reaction sites of Co/Cu-MOF and the ability to control the hydroxyl group adsorption by adjusting the Co/Cu ratio, excellent electrocatalytic sensing performance was ensured. Co/Cu-MOF (Co/Cu molar ratio of 20 : 1) showed the best adsorption capacity for hydroxyl groups with a sensitivity of 0.45 mA mM-1 cm-2 and a LOD of 0.82 µM in electrochemical glucose sensing. In summary, the sensing performance was effectively improved by adding adsorbed hydroxyl groups to provide an oxygen source for the glucose oxidation step without changing the specific components.

The role of LncRNA-regulated autophagy in AKI.

Acute kidney injury (AKI) is a complex clinical syndrome involving a series of pathophysiological processes regulated by multiple pathways at the molecular and cellular level. Long noncoding RNAs (lncRNAs) play an important role in the regulation of epigenetics, and their regulation of autophagy-related genes in AKI has attracted increasing attention. However, the role of lncRNA-regulated autophagy in AKI has not been fully elucidated. Evidence indicated that lncRNAs play regulatory roles in most factors that induce AKI. LncRNAs can regulate autophagy in AKI via a complex network of regulatory pathways to affect the development and prognosis of AKI. This article reviewed and analyzed the pathways of lncRNA regulation of autophagy in AKI in recent years. The results provide new ideas for further study of the pathophysiological process and targeted therapy for AKI.

The Progress in Reconstruction of Mandibular Defect Caused by Osteoradionecrosis.

Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy in at least 3 months. Though traditional theories in the early stage including hypoxic-hypocellular-hypovascular and fibro-atrophic in addition to new findings such as ferroptosis were put forward to explain the mechanisms of the osteoradionecrosis, the etiology of ORN is still unclear. With the high rate of occurrence in the head and neck area, especially in the mandible, this disease can disrupt the shape and function of the irradiated area, leading to a clinical presentation ranging from stable small areas of asymptomatic exposed bone to severe progressive necrosis. In severe cases, patients may experience pain, xerostomia, dysphagia, facial fistulas, and even a jaw defect. Consequently, sequence therapy and sometimes extensive surgery and reconstructions are needed to manage these sequelae. Treatment options may include pain medication, antibiotics, the removal of sequesters, hyperbaric oxygen therapy, segmental resection of the mandible, and free flap reconstruction. Microanastomosed free-flaps are considered to be promising choice for ORN reconstruction in recent researches, and new methods including three-dimensional (3-D) printing, pentoxifylline, and amifostine are used nowadays in trying increase the success rates and improve quality of the reconstruction. This review summarizes the main research progress in osteoradionecrosis and reconstruction treatment of osteoradionecrosis with mandibular defect.

Maxillary Antral Pseudocyst Drift after Osteotome Sinus Floor Elevation with Simultaneous Implant Placement: A Case Report and Literature Review.

This report describes maxillary antral pseudocyst drift after maxillary sinus floor augmentation through osteotome sinus floor elevation with simultaneous implant placement. 3D Slicer was used to measure the pseudocyst and maxilla for the placement of the implants; follow-up visits were scheduled at 6, 12, and 22 months. No adverse effects were observed during or after surgery, and all implants exhibited osseointegration without mobility. At 6 months after surgery, the pseudocyst had moved posterolaterally from the preoperative position near the anterior medial maxillary sinus, then returned to its original position at 12 months. However, it had remigrated to the posterolateral position at 22 months. The preoperative volume of the pseudocyst was 3.795 mm3; it was 2.370, 3.439, and 2.930 mm3 at 6, 12, and 22 months after surgery, respectively. The changes in pseudocyst drift and volume did not have a substantial negative influence on the implants, presumably because of cystic attachment and the recurrence of multiple pseudocysts at different locations. The risks associated with changes in a pseudocyst can be avoided, if an appropriate treatment plan is selected.

Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder, and ferroptosis plays a significant role in the pathological mechanism underlying Parkinson's disease. Rapamycin, an autophagy inducer, has been shown to have neuroprotective effects in Parkinson's disease. However, the link between rapamycin and ferroptosis in Parkinson's disease is not entirely clear. In this study, rapamycin was administered to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson's disease PC12 cell model. The results showed that rapamycin improved the behavioral symptoms of Parkinson's disease model mice, reduced the loss of dopamine neurons in the substantia nigra pars compacta, and reduced the expression of ferroptosis-related indicators (glutathione peroxidase 4, recombinant solute carrier family 7, member 11, glutathione, malondialdehyde, and reactive oxygen species). In the Parkinson's disease cell model, rapamycin improved cell viability and reduced ferroptosis. The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer (methyl (1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate) and an autophagy inhibitor (3-methyladenine). Inhibiting ferroptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects. Therefore, the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson's disease.

Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.

Mitochondria are the structures in cells that are responsible for producing energy. They contain a specific translation unit for synthesizing mitochondria-encoded respiratory chain components: the mitochondrial DNA (mt DNA). Recently, a growing number of syndromes associated with the dysfunction of mt DNA translation have been reported. However, the functions of these diseases still need to be precise and thus attract much attention. Mitochondrial tRNAs (mt tRNAs) are encoded by mt DNA; they are the primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. Previous research has shown the role of mt tRNAs in the epileptic mechanism. This review will focus on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in order to summarize some common relevant mutant genes of mt aaRS that cause epilepsy and the specific symptoms of the disease they cause.

Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis.

Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (-7.6 Kcal/mol and -8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways.

PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma.

Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy.

Comparative genomic analysis reveals differential genomic characteristics and featured genes between rapid- and slow-growing non-tuberculous mycobacteria.

Introduction: Non-tuberculous mycobacteria (NTM) is a major category of environmental bacteria in nature that can be divided into rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM) based on their distinct growth rates. To explore differential molecular mechanisms between RGM and SGM is crucial to understand their survival state, environmental/host adaptation and pathogenicity. Comparative genomic analysis provides a powerful tool for deeply investigating differential molecular mechanisms between them. However, large-scale comparative genomic analysis between RGM and SGM is still uncovered. Methods: In this study, we screened 335 high-quality, non-redundant NTM genome sequences covering 187 species from 3,478 online NTM genomes, and then performed a comprehensive comparative genomic analysis to identify differential genomic characteristics and featured genes/protein domains between RGM and SGM. Results: Our findings reveal that RGM has a larger genome size, more genes, lower GC content, and more featured genes/protein domains in metabolism of some main substances (e.g. carbohydrates, amino acids, nucleotides, ions, and coenzymes), energy metabolism, signal transduction, replication, transcription, and translation processes, which are essential for its rapid growth requirements. On the other hand, SGM has a smaller genome size, fewer genes, higher GC content, and more featured genes/protein domains in lipid and secondary metabolite metabolisms and cellular defense mechanisms, which help enhance its genome stability and environmental adaptability. Additionally, orthogroup analysis revealed the important roles of bacterial division and bacteriophage associated genes in RGM and secretion system related genes for better environmental adaptation in SGM. Notably, PCoA analysis of the top 20 genes/protein domains showed precision classification between RGM and SGM, indicating the credibility of our screening/classification strategies. Discussion: Overall, our findings shed light on differential underlying molecular mechanisms in survival state, adaptation and pathogenicity between RGM and SGM, show the potential for our comparative genomic pipeline to investigate differential genes/protein domains at whole genomic level across different bacterial species on a large scale, and provide an important reference and improved understanding of NTM.