Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Degradation mechanisms and toxicity determination of bisphenol A by FeOx-activated peroxydisulfate under ultraviolet light.

Ultraviolet light (UV)-assisted advanced oxidation processes (AOPs) are commonly used to degrade organic contaminants. However, this reaction system's extensive comprehension of the degradation mechanisms and toxicity assessment remains inadequate. This study focuses on investigating the degradation mechanisms and pathways of bisphenol A (BPA), generation of reactive oxygen species (ROS), and toxicity of degradation intermediates in UV/PDS/ferrous composites (FeOx) systems. The degradation rate of BPA gradually increased from the initial 11.92% to 100% within 120 min. Sulfate radicals (SO4.-), hydroxyl radicals (.OH), superoxide anions (O2.-), and singlet oxygen (1O2) were the primary factors in the photocatalytic degradation of BPA in the UV/PDS/FeOx systems. The main reactions of BPA in this system were deduced to be ß-bond cleavage, hydroxyl substitution reaction, hydrogen bond cleavage, and oxidation reaction. A trend of decreasing toxicity for the degradation intermediates of BPA was observed according to the toxicity investigations. The efficient degradation of BPA in UV/PDS/FeOx systems provided theoretical data for AOPs, which will improve the understanding of organic contaminants by FeOx in natural industry wastewater.

Recent trends in the transfer of graphene films.

Recent years have witnessed advances in chemical vapor deposition growth of graphene films on metal foils with fine scalability and thickness controllability. However, challenges for obtaining wrinkle-free, defect-free and large-area uniformity remain to be tackled. In addition, the real commercial applications of graphene films still require industrially compatible transfer techniques with reliable performance of transferred graphene, excellent production capacity, and suitable cost. Transferred graphene films, particularly with a large area, still suffer from the presence of transfer-related cracks, wrinkles and contaminants, which would strongly deteriorate the quality and uniformity of transferred graphene films. Potential applications of graphene films include moisture barrier films, transparent conductive films, electromagnetic shielding films, and optical communications; such applications call different requirements for the performance of transferred graphene, which, in turn, determine the suitable transfer techniques. Besides the reliable transfer process, automatic machines should be well developed for the future batch transfer of graphene films, ensuring the repeatability and scalability. This mini-review provides a summary of recent advances in the transfer of graphene films and offers a perspective for future directions of transfer techniques that are compatible for industrial batch transfer.

Indole-3-carbinol ameliorates ovarian damage in female old mice through Nrf2/HO-1 pathway activation.

Ovarian aging leads to infertility and birth defects. We aimed to clarify the role of Indole-3-carbinol (I3C) in resistance to oxidative stress, apoptosis, and fibrosis in ovarian aging. I3C was administered via intraperitoneal injection for 3 weeks in young or old mice. Immunohistochemistry; Masson, Sirius red, and TUNEL staining; follicle counting; estrous cycle analysis; and Western blotting were used for validating the protective effect of I3C against ovarian senescence. Human granulosa-like tumor cell line and primary granulosa cells were used for in vitro assay. The results indicated that I3C inhibited ovarian fibrosis and apoptosis while increasing the number of primordial follicles. Mechanistic studies have shown that I3C promoted the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2) and upregulated the expression of heme oxygenase 1 (HO-1). Additionally, I3C increased cell viability and decreased lactate dehydrogenase, malondialdehyde, reactive oxygen species and JC-1 levels. Furthermore, the antioxidant effect of I3C was found to be dependent on the activation of Nrf2 and HO-1, as demonstrated by the disappearance of the effect upon inhibition of Nrf2 expression. In conclusion, I3C can alleviate the ovarian damage caused by aging and may be a protective agent to delay ovarian aging.

Maternal exposure to beta-Cypermethrin disrupts placental development by dysfunction of trophoblast cells from oxidative stress.

As a broad-spectrum and efficient insecticide, beta-Cypermethrin (ß-CYP) poses a health risk to pregnancy. It matters the mechanisms of maternal exposure to ß-CYP for impacting reproductive health. The placenta, a transient organ pivotal for maternal-fetal communication during pregnancy, plays a crucial role in embryonic development. The effect of ß-CYP exposure on the placenta and its underlying molecular mechanisms remain obscure. The objective of this study was to investigate the effect of ß-CYP exposure on placental development and the function of trophoblast, as well as the underlying mechanisms through CD-1 mouse model (1, 10, 20 mg/kg.bw) and in vitro HTR-8/SVneo cell model (12.5, 25, 50, 100 µM). We found slower weight gain and reduced uterine wet weight in pregnant mice with maternal exposure to ß-CYP during pregnancy, as well as adverse pregnancy outcomes such as uterine bleeding and embryo resorption. The abnormal placental development in response to ß-CYP was noticed, including imbalanced placental structure and disrupted labyrinthine vascular development. Trophoblasts, pivotal in placental development and vascular remodeling, displayed abnormal differentiation under ß-CYP exposure. This aberration was characterized by thickened trophoblast layers in the labyrinthine zone, accompanied by mitochondrial and endoplasmic reticulum swelling within trophoblasts. Further researches on human chorionic trophoblast cell lines revealed that ß-CYP exposure induced apoptosis in HTR-8/SVneo cells. This induction resulted in a notable decrease in migration and invasion abilities, coupled with oxidative stress and the inhibition of the Notch signaling pathway. N-acetylcysteine (an antioxidant) partially restored the impaired Notch signaling pathway in HTR-8/SVneo cells, and mitigated cellular functional damage attributed to ß-CYP exposure. Collectively, exposure to ß-CYP induced oxidative stress and then led to inhibition of the Notch signaling pathway and dysfunction of trophoblast cells, ultimately resulted in abnormal placenta and pregnancy. These findings indicate Reactive Oxygen Species as potential intervention targets to mitigate ß-CYP toxicity. The comprehensive elucidation contributes to our understanding of ß-CYP biosafety and offers an experimental basis for preventing and managing its reproductive toxicity.

Sulfonamide disinfection byproducts exhibited severe toxicity to human commensal bacteria.

Many antibiotic disinfection byproducts have been detected but their toxicity has not been evaluated adequately. In this report, the chlorination reaction kinetics of five common sulfamides (SAs), reaction intermediates and their toxicity were investigated. Chlorination of sulfapyridine (SPD), sulfamethazine (SMT), sulfathiazole (STZ), and sulfisoxazole (SIZ) followed the second-order kinetics, and were degraded completely within 10 min. A large number of reaction intermediates were deteced by LC-MS, among which a total of 16 intermediates were detected for the first time. Toxicity of the five SAs chlorination solutions was evaluated separately by examining their effects on the growth rate of S. salivarius K12, a commensal bacterium in the human digestive system. After 30 min chlorination, solutions of SMT, STZ and sulfadiazine (SDZ) each exhibited severe toxicity by inhibiting the bacteria growth completely, whereas the inhibition was only 50 % and 20  % by SIZ and SPD respectively. Based on the comparison between toxicity test results and mass spectra, three SA chlorination intermediates, m/z 187.2 (C10H10N4), m/z 287.2 (C9H7N3O4S2) and m/z 215 (C7H10N4O2S/C12H14N4) were proposed to be the primary toxicants in the chlorination products. Our study demonstrated the power of combined approach of chemical analysis and toxicity testing in identifying toxic disinfection byproducts, and highlighted the ne ed for more research on the toxicity evaluation and risk assessment of antibiotic disinfection byproducts.

B(a)P induces ovarian granulosa cell apoptosis via TRAF2-NFκB-Caspase1 axis during early pregnancy.

Benzo(a)pyrene [B(a)P] is an environmental endocrine disruptor with reproductive toxicity. The corpus luteum (CL) of the ovary plays an important role in embryo implantation and pregnancy maintenance. Our previous studies have shown that B(a)P exposure affects embryo implantation and endometrial decidualization in mouse, but its effects and mechanisms on CL function remain unclear. In this study, we explore the mechanism of ovarian toxicity of B(a)P using a pregnant mouse model and an in vitro model of human ovarian granulosa cells (GCs) KGN. Pregnant mice were gavaged with corn oil or 0.2 mg/kg.bw B(a)P from pregnant day 1 (D1) to D7, while KGN cells were treated with DMSO, 1.0IU/mL hCG, or 1.0IU/mL hCG plus benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), a B(a)P metabolite. Our findings revealed that B(a)P exposure damaged embryo implantation and reduced estrogen and progesterone levels in early pregnant mice. Additionally, in vitro, BPDE impaired luteinization in KGN cells. We observed that B(a)P/BPDE promoted oxidative stress (OS) and inflammation, leading to apoptosis rather than pyroptosis in ovaries and luteinized KGN cells. This apoptotic response was mediated by the activation of inflammatory Caspase1 through the cleavage of BID. Furthermore, B(a)P/BPDE inhibited TRAF2 expression and suppressed NFκB signaling pathway activation. The administration of VX-765 to inhibit the Caspase1 activation, over-expression of TRAF2 using TRAF2-pcDNA3.1 (+) plasmid, and BetA-induced activation of NFκB signaling pathway successfully alleviated BPDE-induced apoptosis and cellular dysfunction in luteinized KGN cells. These findings were further confirmed in the KGN cell treated with H2O2 and NAC. In conclusion, this study elucidated that B(a)P/BPDE induces apoptosis rather than pyroptosis in GCs via TRAF2-NFκB-Caspase1 during early pregnancy, and highlighting OS as the primary contributor to B(a)P/BPDE-induced ovarian toxicity. Our results unveil a novel role of TRAF2-NFκB-Caspase1 in B(a)P-induced apoptosis and broaden the understanding of mechanisms underlying unexplained luteal phase deficiency.

Rubisco small subunit (RbCS) is co-opted by potyvirids as the scaffold protein in assembling a complex for viral intercellular movement.

Plant viruses must move through plasmodesmata (PD) to complete their life cycles. For viruses in the Potyviridae family (potyvirids), three viral factors (P3N-PIPO, CI, and CP) and few host proteins are known to participate in this event. Nevertheless, not all the proteins engaging in the cell-to-cell movement of potyvirids have been discovered. Here, we found that HCPro2 encoded by areca palm necrotic ring spot virus (ANRSV) assists viral intercellular movement, which could be functionally complemented by its counterpart HCPro from a potyvirus. Affinity purification and mass spectrometry identified several viral factors (including CI and CP) and host proteins that are physically associated with HCPro2. We demonstrated that HCPro2 interacts with both CI and CP in planta in forming PD-localized complexes during viral infection. Further, we screened HCPro2-associating host proteins, and identified a common host protein in Nicotiana benthamiana-Rubisco small subunit (NbRbCS) that mediates the interactions of HCPro2 with CI or CP, and CI with CP. Knockdown of NbRbCS impairs these interactions, and significantly attenuates the intercellular and systemic movement of ANRSV and three other potyvirids (turnip mosaic virus, pepper veinal mottle virus, and telosma mosaic virus). This study indicates that a nucleus-encoded chloroplast-targeted protein is hijacked by potyvirids as the scaffold protein to assemble a complex to facilitate viral movement across cells.

Tensile and Interfacial Mechanical Properties for Single Aramid III Fibers under Dynamic Loading.

In this study, the traditional mini split Hopkinson tension bar (SHTB) was enhanced for the dynamic mechanical performance testing of single fiber/resin interface of composites. Single Aramid III fibers were modified using a polyamine modification treatment. Quasi-static and dynamic tensile tests of modified single Aramid III fibers were conducted using an electronic tensile testing machine and mini SHTB. The test results indicated that the surface modification employing the Catechol-Tetraethylenepentamine (Cat-TEPA) approach had a negligible effect on the tensile mechanical properties of single Aramid III fibers. The microdroplet method was introduced to measure the dynamic interfacial shear strength (IFSS) of Aramid III fiber/waterborne polyurethane resin using a mini SHTB. The dynamic shear test results revealed an increase in the dynamic shear strength of the modified Aramid III fiber/resin interface from 36.16 MPa to 41.51 MPa. Furthermore, the Scanning Electron Microscope (SEM) photography of the modified single Aramid III fiber after debonding exhibited regular grid structures on the debonding area, which can prevent debonding between the single fiber and the microdroplet, thereby enhancing interfacial shear performance.

Identification of molecular subtypes and a prognostic signature based on m6A/m5C/m1A-related genes in lung adenocarcinoma.

Lung cancer, specifically the histological subtype lung adenocarcinoma (LUAD), has the highest global occurrence and fatality rate. Extensive research has indicated that RNA alterations encompassing m6A, m5C, and m1A contribute actively to tumorigenesis, drug resistance, and immunotherapy responses in LUAD. Nevertheless, the absence of a dependable predictive model based on m6A/m5C/m1A-associated genes hinders accurately predicting the prognosis of patients diagnosed with LUAD. In this study, we collected patient data from The Cancer Genome Atlas (TCGA) and identified genes related to m6A/m5C/m1A modifications using the GeneCards database. The "ConsensusClusterPlus" R package was used to produce molecular subtypes by utilizing genes relevant to m6A/m5C/m1A identified through differential expression and univariate Cox analyses. An independent prognostic factor was identified by constructing a prognostic signature comprising six genes (SNHG12, PABPC1, IGF2BP1, FOXM1, CBFA2T3, and CASC8). Poor overall survival and elevated expression of human leukocyte antigens and immune checkpoints were correlated with higher risk scores. We examined the associations between the sets of genes regulated by m6A/m5C/m1A and the risk model, as well as the immune cell infiltration, using algorithms such as ESTIMATE, CIBERSORT, TIMER, ssGSEA, and exclusion (TIDE). Moreover, we compared tumor stemness indices (TSIs) by considering the molecular subtypes related to m6A/m5C/m1A and risk signatures. Analyses were performed based on the risk signature, including stratification, somatic mutation analysis, nomogram construction, chemotherapeutic response prediction, and small-molecule drug prediction. In summary, we developed a prognostic signature consisting of six genes that have the potential for prognostication in patients with LUAD and the design of personalized treatments that could provide new versions of personalized management for these patients.

scRNA-Seq and Bulk-Seq Analysis Identifies S100A9 Plasma Cells as a Potentially Effective Immunotherapeutic Agent for Multiple Myeloma.

Purpose: Immunological regimens are an important area of research for treating multiple myeloma (MM). Plasma cells play a crucial role in immunotherapy. Patients and Methods: In our study, we used both single-cell RNA sequencing (scRNA-seq) and bulk sequencing techniques to analyze MM patients. We analyzed each sample using gene set variation analysis (GSVA) based on immune-related gene sets. We also conducted further analyses to compare immune infiltration, clinical characteristics, and expression of immune checkpoint molecules between the H-S100A9 and L-S100A9 groups of MM patients. Results: We identified eight subpopulations of plasma cells, with S100A9 plasma cells being more abundant in patients with 1q21 gain and 1q21 diploid. CellChat analysis revealed that GAS and HGF signaling pathways were prominent in intercellular communication of S100A9 plasma cells. We identified 14 immune-related genes in the S100A9 plasma cell population, which allowed us to classify patients into the H-S100A9 group or the L-S100A9 group. The H-S100A9 group showed higher ESTIMATE, immune and stroma scores, lower tumor purity, and greater immune checkpoint expression. Patients with 1q21 gain and four or more copies had the lowest ESTIMATE score, immune score, stroma score, and highest tumor purity. Drug sensitivity analysis indicated that the H-S100A9 group had lower IC50 values and greater drug sensitivity compared to the L-S100A9 group. Quantitative reverse transcription (RT-q) PCR showed significantly elevated expression of RNASE6, LYZ, S100A8, S100A9, and S100A12 in MM patients compared to the healthy control group. Conclusion: Our study has identified a correlation between molecular subtypes of S100A9 plasma cells and the response to immunotherapy in MM patients. These findings improve our understanding of tumor immunology and provide guidance for developing effective immunotherapy strategies for this patient population.

Unlocking the health potential of anthocyanins: a structural insight into their varied biological effects.

Anthocyanins have become increasingly important to the food industry due to their colorant features and many health-promoting activities. Numerous studies have linked anthocyanins to antioxidant, anti-inflammatory, anticarcinogenic properties, as well as protection against heart disease, certain types of cancer, and a reduced risk of diabetes and cognitive disorders. Anthocyanins from various foods may exhibit distinct biological and health-promoting activities owing to their structural diversity. In this review, we have collected and tabulated the key information from various recent published studies focusing on investigating the chemical structure effect of anthocyanins on their stability, antioxidant activities, in vivo fate, and changes in the gut microbiome. This information should be valuable in comprehending the connection between the molecular structure and biological function of anthocyanins, with the potential to enhance their application as both colorants and functional compounds in the food industry.

Characterization of Fusarium solani associated with tobacco (Nicotiana tabacum L.) root rot in Henan, China.

The aim of this study was to characterize the Fusarium solani species complex (FSSC) population obtained from tobacco roots with root rot symptoms using morphological characteristics, molecular tests, and assessment of pathogenicity. Cultures isolated from roots were white to cream with sparse mycelium on PDA with colony growth of 21.5 ± 0.5 to 29.5 ± 0.5 mm after 3 days. Sporodochia were cream on carnation leaf agar (CLA) and spezieller nährstoffarmer agar (SNA), and macroconidia formed in sporodochia were 3- to 6-septate, straight to slightly curved, with wide central cells, a slightly short blunt apical cell, and a straight to almost cylindrical basal cell with a distinct foot shape, ranging in size from 20.92 to 64.37 µm × 3.91 to 6.57 µm. Microconidia formed on CLA were reniform and fusiform with 0 or 1 to occasionally 2 septa, that formed on long monophialidic conidiogenous cells, with a size range of 5.99 to 32.32 µm × 1.76 to 5.84 µm. Globose to oval chlamydospores were smooth to rough-walled, 6.5 to 13.3 ± 0.37 µm in diameter, terminal or intercalary, single or in pairs, occasionally in short chains on SNA. Molecular tests consisted of sequencing and phylogenetic analysis of the translation elongation factor-1 alpha (EF-1α), RNA polymerase II largest subunit (RPB1), and second largest subunit (RPB2) regions. All the obtained sequences revealed 98.14%~100% identity to Fusarium solani in both Fusarium ID and Fusarium MLST databases. Phylogenetic trees of the EF-1α gene and concatenated three-loci data showed that isolates from tobacco in Henan grouped in the proposed group 5, which is nested within FSSC clade 3 (FSSC 5). Twenty-seven of the 28 isolates caused a root rot of artificially inoculated tobacco seedlings, with a disease index ranging from 15.00 ± 1.67 to 91.11 ± 2.22. Cross pathogenicity tests showed that three representative isolates were virulent to six species of Solanaceae and two of Poaceae, with disease indexes ranging from 6.12 ± 0.56 to 84.44 ± 0.00, indicating that these isolates have a wide host range. The results may inform control of tobacco root rot through improved crop rotations.

Maternal exposure to ZIF-8 derails placental function by inducing trophoblast pyroptosis through neutrophils activation in mice.

Adverse environmental factors during maternal gestation pose a threat to pregnancy. Environmental factors, particularly nanoparticles, can impact pregnancy by causing damage to the placenta. Compared to early gestation, foetuses in late gestation are more robustly developed and at lower risk of adverse effects from environmental factors. Delivery systems for targeted therapy during pregnancy is predominantly focused on their application in late gestation. Zeolitic imidazolate framework-8 (ZIF-8) holds great potential for targeted drug therapy. To evaluate the value of ZIF-8 in targeted treatment of disorders associated with late gestation, it is crucial to investigate the biological effects of ZIF-8 exposure during late gestation. Here, a mouse model exposed to ZIF-8 particles at different doses (5, 10, and 15 mg/kg) during late gestation was constructed. We found that ZIF-8 particles were deposited in the uterus of pregnant mice. ZIF-8 could trigger placental neutrophil aggregation and induce inflammation, which led to trophoblast pyroptosis and impair placental function, adversely affecting the foetus. Neutrophil depletion alleviated placental and foetal damage induced by ZIF-8. This study provides a novel mechanistic view of the reproductive toxicity induced by ZIF-8 and may offer clues to reduce the latent harm of adverse environmental factors to pregnancy.

Case of clear-cell oncocytoma of parotid gland and literature review.

Oncocytoma is a benign tumor of the salivary gland. Its incidence is very low and very seldom documen-ted in literature. Clear-cell dominant oncocytoma is even less common. The tumor's clinical symptoms and imaging results are nonspecific, so distinguishing other salivary gland tumors (such as oncocytic carcinoma) from clear-cell renal carcinoma is difficult, possibly leading to misdiagnosis and maltreatment. Here, a case of clear-cell dominant oncocytoma was presented, and the relevant literature was evaluated to investigate the diagnosis and management of clear-cell dominant oncocytoma.

Molecular characterization and pathogenicity of a novel monopartite geminivirus infecting tobacco in China.

The occurrence of geminiviruses causes significant economic losses in many economically important crops. In this study, a novel geminivirus isolated from tobacco in Sichuan province of China, named tomato leaf curl Chuxiong virus (TLCCxV), was characterized by small RNA-based deep sequencing. The full-length of TLCCxV genome was determined to be 2744 nucleotides (nt) encoding six open reading frames. Phylogenetic and genome-wide pairwise identity analysis revealed that TLCCxV shared less than 91% identities with reported geminiviruses. A TLCCxV infectious clone was constructed and successfully infected Nicotiana benthamiana, N. tabacum, N. glutinosa, Solanum lycopersicum and Petunia hybrida plants. Furthermore, expression of the V2, C1 and C4 proteins through a potato virus X vector caused severe chlorosis or necrosis symptom in N. benthamiana. Taken together, we identified a new geminivirus in tobacco plants, and found that V2, C1 and C4 contribute to symptom development.

A Synergistic Bimetallic Ti/Co-Catalyzed Isomerization of Epoxides to Allylic Alcohols Enabled by Two-State Reactivity.

Isomerization of epoxides into versatile allylic alcohols is an atom-economical synthetic method to afford vicinal bifunctional groups. Comprehensive density functional theory (DFT) calculations were carried out to elucidate the complex mechanism of a bimetallic Ti/Co-catalyzed selective isomerization of epoxides to allyl alcohols by examining several possible pathways. Our results suggest a possible mechanism involving (1) radical-type epoxide ring opening catalyzed by Cp2Ti(III)Cl leading to a Ti(IV)-bound ß-alkyl radical, (2) hydrogen-atom transfer (HAT) catalyzed by the Co(II) catalyst to form the Ti(IV)-enolate and Co(III)-H intermediate, (3) protonation to give the alcohols, and (4) proton abstraction to form the Co(I) species followed by electron transfer to regenerate the active Co(II) and Ti(III) species. Moreover, bimetallic catalysis and two-state reactivity enable the key rate-determining HAT step. Furthermore, a subtle balance between dispersion-driven bimetallic processes and entropy-driven monometallic processes determines the most favorable pathway, among which the monometallic process is energetically more favorable in all steps except the vital hydrogen-atom transfer step. Our study should provide an in-depth mechanistic understanding of bimetallic catalysis.

Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. HACE1 interacts with its substrates, including Ras-related C3 botulinum toxin substrate 1 (Rac1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor receptor (TNFR), and optineurin (OPTN), through which participates in several pathophysiological processes, such as oxidative stress, autophagy and inflammation. Therefore, in this review, we elaborately describe the essential substrates of HACE1 and illuminate the pathophysiological processes by which HACE1 is involved in neurodegenerative diseases. We provide a new molecular target for neurodegenerative diseases.

Application of Acetate as a Substrate for the Production of Value-Added Chemicals in Escherichia coli.

At present, the production of the majority of valuable chemicals is dependent on the microbial fermentation of carbohydrate substrates. However, direct competition is a potential problem for microbial feedstocks that are also used within the food/feed industries. The use of alternative carbon sources, such as acetate, has therefore become a research focus. As a common organic acid, acetate can be generated from lignocellulosic biomass and C1 gases, as well as being a major byproduct in microbial fermentation, especially in the presence of an excess carbon source. As a model microorganism, Escherichia coli has been widely applied in the production of valuable chemicals using different carbon sources. Recently, several valuable chemicals (e.g., succinic acid, itaconic acid, isobutanol, and mevalonic acid) have been investigated for synthesis in E. coli using acetate as the sole carbon source. In this review, we summarize the acetate metabolic pathway in E. coli and recent research into the microbial production of chemical compounds in E. coli using acetate as the carbon source. Although microbial synthetic pathways for different compounds have been developed in E. coli, the production titer and yield are insufficient for commercial applications. Finally, we discuss the development prospects and challenges of using acetate for microbial fermentation.