Upregulation of NPC1 and its association with poor prognosis in gastric cancer.

BACKGROUND: The Niemann-Pick disease type C1 (NPC1) protein plays a pivotal role in lipid transport, particularly free cholesterol, within lysosomal/late endosomal membranes. Previous studies have highlighted NPC1 as a promising target for cholesterol trafficking and cancer therapy. Nevertheless, the expression of NPC1 in gastric cancer (GC) and its clinical implications remain unexplored. This study aims to investigate NPC1 expression in GC and its correlation with patient prognosis. METHODS: NPC1 expression levels in GC and normal tissues were assessed using the GEPIA database, and survival analysis was conducted via Kaplan‒Meier Plotter. Evaluation of potential biological effects of NPC1 in GC by protein-protein interaction network and GO, KEGG bioenrichment analysis. Immunohistochemistry was performed on surgical samples collected from 306 GC patients. Correlations between NPC1 expression, clinical characteristics, and patient prognosis were analyzed. RESULTS: NPC1 mRNA expression was elevated in GC tissues compared to normal tissues (P < 0.05) and significantly associated with poorer prognosis. In our cohort of 306 patients, NPC1 exhibited significant upregulation in GC versus adjacent normal tissues (P = 0.031). High NPC1 expression correlated with adverse clinical characteristics, including lymph node metastasis, distant metastasis, and advanced TNM stage (all P < 0.05). Patients with high NPC1 expression experienced notably shorter overall survival (P < 0.001), particularly in stages III and IV (P = 0.003). Multivariate Cox regression analysis identified high NPC1 expression as an independent prognostic factor for GC patients (HR 1.57, 95% CI 1.14-2.18, P = 0.006). Lastly, an optimized nomogram incorporating NPC1, tumor size, and TNM stage was constructed. CONCLUSIONS: NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.

MEF2C contributes to axonal branching by regulating Kif2c transcription.

Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.

Hepatocyte-specific METTL3 ablation by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and postnatal lethality.

AIM: In 2019, to examine the functions of METTL3 in liver and underlying mechanisms, we generated mice with hepatocyte-specific METTL3 homozygous knockout (METTL3Δhep) by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT) or Alb-Cre mice (JAX), respectively. In this study, we explored the potential reasons why hepatocyte-specific METTL3 homozygous disruption by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and then postnatal lethality. MAIN METHODS: Mice with hepatocyte-specific METTL3 knockout were generated by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT; Strain No. T003814) purchased from the GemPharmatech Co., Ltd., (Nanjing, China) or with Alb-Cre mice (JAX; Strain No. 003574) obtained from The Jackson Laboratory, followed by combined-phenotype analysis. The publicly available RNA-sequencing data deposited in the NCBI Gene Expression Omnibus (GEO) database under the accession No.: GSE198512 (postnatal lethality), GSE197800 (postnatal survival) and GSE176113 (postnatal survival) were mined to explore the potential reasons why hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), leads to ALF and then postnatal lethality. KEY FINDINGS: Firstly, we observed that hepatocyte-specific METTL3 homozygous deficiency by Alb-iCre mice (GPT) or by Alb-Cre mice (JAX) caused liver injury, abnormal lipid accumulation and apoptosis. Secondly, we are surprised to find that hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), led to ALF and then postnatal lethality. Our findings clearly demonstrated that METTL3Δhep mice (GPT), which are about to die, exhibited the severe destruction of liver histological structure, suggesting that METTL3Δhep mice (GPT) nearly lose normal liver function, which subsequently contributes to ALF, followed by postnatal lethality. Finally, we unexpectedly found that as the compensatory growth responses of hepatocytes to liver injury induced by METTL3Δhep (GPT), the proliferation of METTL3Δhep hepatocytes (GPT), unlike METTL3Δhep hepatocytes (JAX), was not evidenced by the significant increase of Ki67-positive hepatocytes, not accompanied by upregulation of cell-cycle-related genes. Moreover, GO analysis revealed that upregulated genes in METTL3Δhep livers (GPT), unlike METTL3Δhep livers (JAX), are not functionally enriched in terms associated with cell cycle, cell division, mitosis, microtubule cytoskeleton organization, spindle organization, chromatin segregation and organization, and nuclear division, consistent with the loss of compensatory proliferation of METTL3Δhep hepatocytes (GPT) observed in vivo. Thus, obviously, the loss of the compensatory growth capacity of METTL3Δhep hepatocytes (GPT) in response to liver injury might contribute to, at least partially, ALF and subsequently postnatal lethality of METTL3Δhep mice (GPT). SIGNIFICANCE: These findings from this study and other labs provide strong evidence that these phenotypes (i.e., ALF and postnatal lethality) of METTL3Δhep mice (GPT) might be not the real functions of METTL3, and closely related with Alb-iCre mice (GPT), suggesting that we should remind researchers to use Alb-iCre mice (GPT) with caution to knockout gene in hepatocytes in vivo.

Mitigating ash-related alkali and heavy metals emissions in rotary kiln through oxygen-carrier-aided combustion of waste.

Rotary kiln (RK) incineration technology gains prominence in waste management, aiming to reduce pollution, recover energy, and minimize waste. Oxygen-carrier (OC)-aided incineration of waste in the RK demonstrates notable benefits by enhancing oxygen distribution uniformity and facilitating fuel conversion. However, the effects of OC on ash-related alkali and heavy metals during waste incineration in the RK remain unknown. In this study, manganese ore and ilmenite as OCs are introduced into RK during waste combustion, focusing on their effects on the bottom ashes and the behavior of alkali and heavy metals. Results show that manganese ore exhibits a decreasing reactivity due to oxygen depletion during the conversion from Mn2O3 to Mn3O4, while ilmenite maintains good reactivity due to sustained enrichment of Fe2O3 on the particles even after multiple cycles in RK. The porous structure on the surface of OCs particles verifies the cyclic reaction involving oxidation by air and reduction by fuel as OCs move between the active and passive layers of the bed. The porous OCs particles offer abundant adsorption sites for K from the gaseous phase, with surface-deposited K migrating into the particles and enhancing the OCs' capacity for K adsorption. Adding OCs promotes the formation of stable, less volatile compounds of heavy metals (As, Cr, Pb, and Zn) and enhances their retention in bottom ash while ensuring the leaching toxicity remains below Chinese national standard limits. This study enhances the understanding of OCs in incineration, guiding vital references for waste management practices and environmental sustainability.

The Anti-inflammatory Potential of a Strain of Probiotic Bifidobacterium pseudocatenulatum G7: In Vitro and In Vivo Evidence.

The genus Bifidobacterium has been widely used in functional foods for health promotion due to its beneficial effects on human health, especially in the gastrointestinal tract (GIT). In this study, we characterize the anti-inflammatory potential of the probiotic strain Bifidobacterium pseudocatenulatum G7, isolated from a healthy male adult. G7 secretion inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Moreover, oral administration of bacteria G7 alleviated the severity of colonic inflammation in dextran sulfate sodium (DSS)-treated colitis mice, which was evidenced by a decreased disease activity index (DAI) and enhanced structural integrity of the colon. The 16S rRNA gene sequencing result illustrated that the G7 alleviated DSS-induced gut microbiota dysbiosis, accompanied by the modulated bile acids and short-chain fatty acid (SCFA) levels. Overall, our results demonstrated the potential anti-inflammatory effects of Bifidobacterium pseudocatenulatum G7 on both in vitro and in vivo models, which provided a solid foundation for further development of a novel anti-inflammatory probiotic.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Nucleoporin Seh1 controls murine neocortical development via transcriptional repression of p21 in neural stem cells.

Mutations or dysregulation of nucleoporins (Nups) are strongly associated with neural developmental diseases, yet the underlying mechanisms remain poorly understood. Here, we show that depletion of Nup Seh1 in radial glial progenitors results in defective neural progenitor proliferation and differentiation that ultimately manifests in impaired neurogenesis and microcephaly. This loss of stem cell proliferation is not associated with defects in the nucleocytoplasmic transport. Rather, transcriptome analysis showed that ablation of Seh1 in neural stem cells derepresses the expression of p21, and knockdown of p21 partially restored self-renewal capacity. Mechanistically, Seh1 cooperates with the NuRD transcription repressor complex at the nuclear periphery to regulate p21 expression. Together, these findings identified that Nups regulate brain development by exerting a chromatin-associated role and affecting neural stem cell proliferation.

PINK1 dominated mitochondria associated genes signature predicts abdominal aortic aneurysm with metabolic syndrome.

Abdominal aortic aneurysm (AAA) is typically asymptomatic but a devastating cardiovascular disorder, with overall mortality exceeding 80 % once it ruptures. Some patients with AAA may also have comorbid metabolic syndrome (MS), suggesting a potential common underlying pathogenesis. Mitochondrial dysfunction has been reported as a key factor contributing to the deterioration of both AAA and MS. However, the intricate interplay between metabolism and mitochondrial function, both contributing to the development of AAA, has not been thoroughly explored. In this study, we identified candidate genes related to mitochondrial function in AAA and MS. Subsequently, we developed a nomoscore model comprising hub genes (PINK1, ACSL1, CYP27A1, and SLC25A11), identified through the application of two machine learning algorithms, to predict AAA. We observed a marked disparity in immune infiltration profiles between high- and low-nomoscore groups. Furthermore, we confirmed a significant upregulation of the expression of the four hub genes in AAA tissues. Among these, ACSL1 showed relatively higher expression in LPS-treated RAW264.7 cell lines, while CYP27A1 exhibited a notable decrease. Moreover, SLC25A11 displayed a significant upregulation in AngII-treated VSMCs. Conversely, the expression level of PINK1 declined in LPS-stimulated RAW264.7 cell lines but significantly increased in AngII-treated VSMCs. In vivo experiments revealed that the activation of PINK1-mediated mitophagy inhibited the development of AAA in mice. In this current study, we have innovatively identified four mitochondrial function-related genes through integrated bioinformatic analysis. This discovery sheds light on the regulatory mechanisms and unveils promising therapeutic targets for the comorbidity of AAA and MS.

Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta, with a high mortality rate when rupturing. Although lots of piRNA pathway genes (piRPGs) have recently been linked to both neoplastic and non-neoplastic illnesses, their role in AAA is still unknown. Utilizing integrative bioinformatics methods, this research discovered piRPGs as biomarkers for AAA and explore possible molecular mechanisms. METHODS: The datasets were obtained from the Gene Expression Omnibus and piRPGs were identified from the Genecards database. The "limma" and "clusterProfiler" R-packages were used to discover differentially expressed genes and perform enrichment analysis, respectively. Hub piRPGs were further filtered using least absolute shrinkage and selection operator regression, random forests, as well as receiver operating characteristic curve. Additionally, multi-factor logistic regression (MLR), extreme gradient boosting (XGboost), and artificial neural network (ANN) were employed to construct prediction models. The relationship between hub piRPGs and immune infiltrating cells and sgGSEA were further studied. The expression of hub piRPGs was verified by qRT-PCR, immunohistochemistry, and western blotting in AAA and normal vascular tissues and analyzed by scRNA-seq in mouse AAA model. SRAMP and cMAP database were utilized for the prediction of N6-methyladenosine (m6A) targets therapeutic drug. RESULTS: 34 differentially expressed piRPGs were identified in AAA and enriched in pathways of immune regulation and gene silence. Three piRPGs (PPP1R12B, LRP10, and COL1A1) were further screened as diagnostic genes and used to construct prediction model. Compared with MLR and ANN, Xgboost showed better predictive ability, and PPP1R12B might have the ability to distinguish small and large AAA. Furthermore, the expression levels of PPP1R12B and COL1A1 were consistent with the results of bioinformatics analysis, and PPP1R12B showed a downward trend that may be related to m6A. CONCLUSION: The results suggest that piRPGs might serve a significant role in AAA. PPP1R12B, COL1A1, and LRP10 had potential as diagnostic-specific biomarkers for AAA and performed better in XGboost model. The expression and localization of PPP1R12B and COL1A1 were experimentally verified. Besides, downregulation of PPP1R12B caused by m6A might contribute to the formation of AAA.

Hip Exoskeleton Based Indirect Intervention Strategy Towards Gait Training After Total Knee Arthroplasty.

Total Knee Arthroplasty (TKA) is the most effective approach for function restoration in patients with severe knee osteoarthritis. However, kinematic, kinetic and muscle activation differences between post-TKA patients and healthy people can be observed in many studies. Exoskeletons have been applied to post-TKA rehabilitation for many years, while few studies concentrated on the stance phase abnormality, neither in the aspect of kinematics nor in muscle activation. In this paper, we propose an indirect resistance strategy for post-operative TKA patient gait training. Three healthy subjects were asked to wear the hip exoskeleton and provided with 8 N·m resistance on the hip extension phase of the gait cycle. The intervention leads to an increment in the knee extension muscle activity as well as the augmentation in maximum knee angle in loading response. The results indicated that the application of resistance in the hip extension phase is a potential therapeutic approach for post-TKA rehabilitation, and may increase the gait training efficiency in the near future.

Robotic Brace Based Multi-Dimensional Assessment for Trunk Ability: A Preliminary Study in Patients with Spinal Cord Injury.

Evaluating trunk control ability is significant in guiding patients towards proper functional training. Most existing devices have only a singular assessment function, resulting in prolonged and asynchronous assessments. Devices with multi-dimensional assessment capabilities may address these limitations. This study utilizes a robotic brace, RoboBDsys-II, to assess the trunk ability of individuals with spinal disorders and to validate its effectiveness. The device can simultaneously collect kinematic, kinetic, and center of pressure data, reducing the assessment time and enabling the simultaneous assessment. The force platform is designed to measure the center of pressure and the force control of the parallel module is developed for the coronal movement assessment. Four patients with spinal cord injury participated in the study to assess their trunk range of motion and muscle strength. Results demonstrate that the trunk range of motion determines the center of pressure metrics in lateral bending experiments. Furthermore, RoboBDsys-II exhibits excellent test-retest reliability in lateral bending experiments and can reveal the muscle strength differences in different directions. The system has potential advantage in the trunk ability assessment.

A Learning-Free Method for Locomotion Mode Prediction by Terrain Reconstruction and Visual-Inertial Odometry.

This research introduces a novel, highly precise, and learning-free approach to locomotion mode prediction, a technique with potential for broad applications in the field of lower-limb wearable robotics. This study represents the pioneering effort to amalgamate 3D reconstruction and Visual-Inertial Odometry (VIO) into a locomotion mode prediction method, which yields robust prediction performance across diverse subjects and terrains, and resilience against various factors including camera view, walking direction, step size, and disturbances from moving obstacles without the need of parameter adjustments. The proposed Depth-enhanced Visual-Inertial Odometry (D-VIO) has been meticulously designed to operate within computational constraints of wearable configurations while demonstrating resilience against unpredictable human movements and sparse features. Evidence of its effectiveness, both in terms of accuracy and operational time consumption, is substantiated through tests conducted using open-source dataset and closed-loop evaluations. Comprehensive experiments were undertaken to validate its prediction accuracy across various test conditions such as subjects, scenarios, sensor mounting positions, camera views, step sizes, walking directions, and disturbances from moving obstacles. A comprehensive prediction accuracy rate of 99.00% confirms the efficacy, generality, and robustness of the proposed method.

Nuclear import carrier Hikeshi cooperates with HSP70 to promote murine oligodendrocyte differentiation and CNS myelination.

Dysregulation of factors in nucleocytoplasmic transport is closely linked to neural developmental diseases. Mutation in Hikeshi, encoding a nonconventional nuclear import carrier of heat shock protein 70 family (HSP70s), leads to inherited leukodystrophy; however, the pathological mechanisms remain elusive. Here, we showed that Hikeshi is essential for central nervous system (CNS) myelination. Deficiency of Hikeshi, which is observed in inherited leukodystrophy patients, resulted in murine oligodendrocyte maturation arrest. Hikeshi is required for nuclear translocation of HSP70s upon differentiation. Nuclear-localized HSP70 promotes murine oligodendrocyte differentiation and remyelination after white matter injury. Mechanistically, HSP70s interacted with SOX10 in the nucleus and protected it from E3 ligase FBXW7-mediated ubiquitination degradation. Importantly, we discovered that Hikeshi-dependent hyperthermia therapy, which induces nuclear import of HSP70s, promoted oligodendrocyte differentiation and remyelination following in vivo demyelinating injury. Overall, these findings demonstrate that Hikeshi-mediated nuclear translocation of HSP70s is essential for myelinogenesis and provide insights into pathological mechanisms of Hikeshi-related leukodystrophy.

SASH1 contributes to glial cell migration in the early development of the central nervous system.

SAM and SH3 domain-containing 1 (SASH1), a member of the SLy protein family, is a tumor suppressor gene that has been studied for its association with various cancers. SASH1 is highly expressed in the mammalian central nervous system, particularly in glial cells, and is expressed in the central nervous system during zebrafish embryo development. However, SASH1's role in brain development has rarely been investigated. In this study, Morpholino oligonucleotides (MO) were used to down-regulate sash1a expression in zebrafish to observe morphological changes in the brain. Three transgenic zebrafish lines, Tg(gfap:eGFP), Tg(hb9:eGFP), and Tg(coro1a:eGFP) were selected to observe changes in glial cells, neurons, and immune cells after sash1a knockdown. Our results showed that the number of microglia residing in the developmental brain was reduced, whereas the axonal growth of caudal primary motor neurons was unaffected by sash1a downregulation. And more significantly, the gfap + glia presented abnormal arrangements and disordered orientations in sash1a morphants. The similar phenotype was verified in the mutation induced by the injection of cas9 mRNA and sash1a sgRNA. We further performed behavioral experiments in zebrafish larvae that had been injected with sash1a MO at one-cell stage, and found them exhibiting abnormal behavior trajectories. Moreover, injecting the human SASH1 mRNA rescued these phenomena in sash1a MO zebrafish. In summary, our study revealed that the downregulation of SASH1 leads to malformations in the embryonic brain and disorganization of glial cell marshalling, suggesting that SASH1 plays an important role in the migration of glial cells during embryonic brain development.

Large field-of-view thermal imaging via all-silicon meta-optics.

A broad range of imaging and sensing technologies in the infrared require large field-of-view (FoV) operation. To achieve this, traditional refractive systems often employ multiple elements to compensate for aberrations, which leads to excess size, weight, and cost. For many applications, including night vision eye-wear, air-borne surveillance, and autonomous navigation for unmanned aerial vehicles, size and weight are highly constrained. Sub-wavelength diffractive optics, also known as meta-optics, can dramatically reduce the size, weight, and cost of these imaging systems, as meta-optics are significantly thinner and lighter than traditional refractive lenses. Here, we demonstrate 80° FoV thermal imaging in the long-wavelength infrared regime (8-12 µm) using an all-silicon meta-optic with an entrance aperture and lens focal length of 1 cm.

Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility.

Endometriosis is strongly associated with infertility. Several mechanisms have been reported in an attempt to elucidate the pathophysiological effects that lead to reduced fertility in women with endometriosis. However, the mechanisms by which endometriosis affects fertility have not been fully elucidated. Ferroptosis is a novel form of nonapoptotic cell death that is characterized by iron-dependent lipid peroxidation membrane damage. In past reports, elevated iron levels in ectopic lesions, peritoneal fluid and follicular fluid have been reported in patients with endometriosis. The high-iron environment is closely associated with ferroptosis, which appears to exhibit a double-edged effect on endometriosis. Ferroptosis can cause damage to ovarian granulosa cells, oocytes, and embryos, leading to endometriosis-related infertility. This article summarizes the main pathways and regulatory mechanisms of ferroptosis and explores the possible mechanisms of the formation of an iron-overloaded environment in endometriotic ectopic lesions, peritoneal fluid and follicular fluid. Finally, we reviewed recent studies on the main and potential mechanisms of ferroptosis in endometriosis and endometriosis-related infertility.

Evolutionary Rates, Divergence Rates, and Performance of Individual Mitochondrial Genes Based on Phylogenetic Analysis of Copepoda.

Copepoda is a large and diverse group of crustaceans, which is widely distributed worldwide. It encompasses roughly 9 orders, whose phylogeny remains unresolved. We sequenced the complete mitochondrial genome (mitogenome) of Sinergasilus major (Markevich, 1940) and used it to explore the phylogeny and mitogenomic evolution of Copepoda. The mitogenome of S. major (14,588 bp) encodes the standard 37 genes as well as a putative control region, and molecular features are highly conserved compared to other Copepoda mitogenomes. Comparative analyses indicated that the nad2 gene has relatively high nucleotide diversity and evolutionary rate, as well as the largest amount of phylogenetic information. These results indicate that nad2 may be a better marker to investigate phylogenetic relationships among closely related species in Copepoda than the commonly used cox1 gene. The sister-group relationship of Siphonostomatoida and Cyclopoida was recovered with strong support in our study. The only topological ambiguity was found within Cyclopoida, which might be caused by the rapid evolution and sparse taxon sampling of this lineage. More taxa and genes should be used to reconstruct the Copepoda phylogeny in the future.

Binary Ni-Co-Based Layered Double Hydroxide Nanoneedle Arrays for High Performance of Oxygen Evolution Reaction.

Low-cost and high-performance electrocatalysts are crucial for water-splitting reactions. Some non-precious metal electrocatalysts are proved to be good replacements for noble metal due to the unique electronic structure features and excellent performance. In this work, binary Ni-Co-based layered double hydroxide nanoneedle arrays electrocatalysts are synthesized on Ni foam (NF) via a hydrothermal process. The microstructure and the catalytic performance of the catalyst changes significantly by regulating the molar ratio of Ni/Co. The theoretical analysis confirmed that the as-prepared NiCo-LDH nanoneedle arrays reveal a potential behavior in oxygen evolution reaction (OER) at a lower overpotential of 305 mV at 10.0 mA cm-2 and a Tafel slope of 110.38 mV dec-1. The double-layer capacitance (Cdl) is 776 mF cm-2, which indicates that there are many active sites that are exposed on the surface for the electrocatalytic reaction. The results provide an obvious reference value to other types of LDH catalysts for the development of water electrolysis.

Performance Study of Diamond Powder-Filled Sodium Silicate-Based Thermal Conductive Adhesives.

With the development of miniaturized, highly integrated, and multifunctional electronic devices, the heat flow per unit area has increased dramatically, making heat dissipation a bottleneck in the development of the electronics industry. The purpose of this study is to develop a new inorganic thermal conductive adhesive to overcome the contradiction between the thermal conductivity and mechanical properties of organic thermal conductive adhesives. In this study, an inorganic matrix material, sodium silicate, was used, and diamond powder was modified to become a thermal conductive filler. The influence of the content of diamond powder on the thermal conductive adhesive properties was studied through systematic characterization and testing. In the experiment, diamond powder modified by 3-aminopropyltriethoxysilane coupling agent was selected as the thermal conductive filler and filled into a sodium silicate matrix with a mass fraction of 34% to prepare a series of inorganic thermal conductive adhesives. The thermal conductivity of the diamond powder and its content on the thermal conductivity of the adhesive were studied by testing the thermal conductivity and taking SEM photos. In addition, X-ray diffraction, infrared spectroscopy, and EDS testing were used to analyze the composition of the modified diamond powder surface. Through the study of diamond content, it was found that as the diamond content gradually increases, the adhesive performance of the thermal conductive adhesive first increases and then decreases. The best adhesive performance was achieved when the diamond mass fraction was 60%, with a tensile shear strength of 1.83 MPa. As the diamond content increased, the thermal conductivity of the thermal conductive adhesive first increased and then decreased. The best thermal conductivity was achieved when the diamond mass fraction was 50%, with a thermal conductivity coefficient of 10.32 W/(m·K). The best adhesive performance and thermal conductivity were achieved when the diamond mass fraction was between 50% and 60%. The inorganic thermal conductive adhesive system based on sodium silicate and diamond proposed in this study has outstanding comprehensive performance and is a promising new thermal conductive material that can replace organic thermal conductive adhesives. The results of this study provide new ideas and methods for the development of inorganic thermal conductive adhesives and are expected to promote the application and development of inorganic thermal conductive materials.

Mettl3-mediated m6A modification plays a role in lipid metabolism disorders and progressive liver damage in mice by regulating lipid metabolism-related gene expression.

AIMS: N6-methyladenosine (m6A), the most abundant and conserved epigenetic modification of mRNA, participates in various physiological and pathological processes. However, the roles of m6A modification in liver lipid metabolism have yet to be understood entirely. We aimed to investigate the roles of the m6A "writer" protein methyltransferase-like 3 (Mettl3) in liver lipid metabolism and the underlying mechanisms. MAIN METHODS: We assessed the expression of Mettl3 in liver tissues of diabetes (db/db) mice, obese (ob/ob) mice, high saturated fat-, cholesterol-, and fructose-induced non-alcoholic fatty liver disease (NAFLD) mice, and alcohol abuse and alcoholism (NIAAA) mice by quantitative reverse-transcriptase PCR (qRT-PCR). Hepatocyte-specific Mettl3 knockout mice were used to evaluate the effects of Mettl3 deficiency in mouse liver. The molecular mechanisms underlying the roles of Mettl3 deletion in liver lipid metabolism were explored by multi-omics joint analysis of public data from the Gene Expression Omnibus database and further validated by qRT-PCR and Western blot. KEY FINDINGS: Significantly decreased Mettl3 expression was associated with NAFLD progression. Hepatocyte-specific knockout of Mettl3 resulted in significant lipid accumulation in the liver, increased serum total cholesterol levels, and progressive liver damage in mice. Mechanistically, loss of Mettl3 significantly downregulated the expression levels of multiple m6A-modified mRNAs related to lipid metabolism, including Adh7, Cpt1a, and Cyp7a1, further promoting lipid metabolism disorders and liver injury in mice. SIGNIFICANCE: In summary, our findings demonstrate that the expression alteration of genes related to lipid metabolism by Mettl3-mediated m6A modification contributes to the development of NAFLD.