Characteristics of the complete mitochondrial genome of Gerres limbatus (Cuvier, 1830) (Perciformes: Gerreidae).

The saddleback silver-biddy Gerres limbatus (Cuvier 1830) is distributed in Indo-West Pacific Oceans and associated with shallow coastal marine waters and estuaries. In this study, the complete mitochondrial genome of G. limbatus was firstly documented, which is 16,730 bp in length, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The overall base composition of the mitochondrial genome is 26.42% A, 28.68% C, 27.32% T, and 17.58% G. The Maximum Likelihood phylogenetic tree was constructed based on COI gene of the 31 species from the family Gerreidae, with Heteroclinus puellarum and Hypopterus macropterus as outgroups. It revealed that G. erythrourus was placed as the sister group to G. limbatus.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Membrane-Based Preparation Process and Antioxidant and Anti-AGEs Activities of a Novel Propolis Ultrafiltrate.

Propolis is one functional supplement with hundreds of years of usage. However, it's rarely consumed directly for its resinous property. Herein, a pre-treated process which can remove the impurity while preserve its bioactivities is needed to maximise its therapeutic opportunities. In the present study, a membrane-based ultrafiltration process was developed on a KM1812-NF experimental instrument. Using Brazilian green propolis as testing material, all experimental steps and parameters were sequentially optimized. In addition, a mathematical model was developed to fit the process. As a result, the optimum solvent was 60 % ethanol adjusted to pH 8-9, while the optimum MWCO (molecular weight cut-off) value of membrane was 30 KDa. The membrane filtration dynamic model fitted with the function y=(ax+b)/(1+cx+dx2 ). The resulting propolis ultrafiltrate from Brazilian green propolis, termed P30K, contains the similar profile of flavonoids and phenolic acids as raw propolis. Meanwhile, the ORAC (oxygen radical absorbance capacity) value of P30K is 11429.45±1557.58 µM TE/g and the IC50 value of inhibition of fluorescent AGEs (advanced glycation end products) formation is 0.064 mg/mL. Our work provides an innovative alternative process for extraction of active compounds from propolis and reveals P30K as an efficient therapeutic antioxidant.

[Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome].

OBJECTIVE: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome. METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis. RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%. CONCLUSION: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

Microarray meta-analysis reveals comprehensive effects of 3,4,5-tricaffeolyquinic acid in cell differentiation and signaling.

Caffeoylquinic acids (CQA) are polyphenolic compounds found in fruits, vegetables, coffee, and spices that have exhibited several beneficial activities, including antioxidant, antibacterial, neuroprotective, anti-inflammatory, anticancer, antiviral, antidiabetic, and cardiovascular effects. A derivative, TCQA (3,4,5-Tri-O-caffeoylquinic acid), has also shown both neurogenic and pigment differentiation potential. A transcriptomic-based meta-analysis was conducted to explore potential biochemical processes and molecular targets of TCQA. This approach involved integrating data from various cell and tissue types, including human amniotic stem cells, human neural stem cells, human dermal papilla cells, and the brain cortex of aging model mice. It offered a comprehensive perspective on the significant gene regulations in response to TCQA treatment. The objective was to uncover the mechanism and novel targets of TCQA, facilitating a further understanding of its functions. New areas of interest found were TCQA's effect on adipogenesis, heart, and muscle tissue development. In addition, significantly enhanced biological activities found through meta-analysis included cell cycle, VEGFA-VEGFR2 pathway, and BMP signaling. Overall, a comprehensive functional and visual analysis using available biological databases uncovered the multi-target potential of this natural compound.

The Effect of Lithium Ion Leaching from Calcined Li-Al Hydrotalcite on the Rapid Removal of Ni2+/Cu2+ from Contaminated Aqueous Solutions.

A layered double hydroxide (LDH) calcined-framework adsorbent was investigated for the rapid removal of heavy metal cations from plating wastewater. Li-Al-CO3 LDH was synthesized on an aluminum lathe waste frame surface to prepare the sorbent. The calcination treatment modified the LDH surface properties, such as the hydrophilicity and the surface pH. The change in surface functional groups and the leaching of lithium ions affected the surface properties and the adsorption capacity of the heavy metal cations. A zeta potential analysis confirmed that the 400 °C calcination changed the LDH surface from positively charged (+10 mV) to negatively charged (-17 mV). This negatively charged surface contributed to the sorbent instantly bonding with heavy metal cations in large quantities, as occurs during contact with wastewater. The adsorption isotherms could be fitted using the Freundlich model. The pseudo-second-order model and the rate-controlled liquid-film diffusion model successfully simulated the adsorption kinetics, suggesting that the critical adsorption step was a heterogeneous surface reaction. This study also confirmed that the recovered nickel and/or copper species could be converted into supported metal nanoparticles with a high-temperature hydrogen reduction treatment, which could be reused as catalysts.

Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression in macrophages by activating NF-κB pathway, and ITA produced by ACOD1 inhibits TET DNA dioxygenases to dampen the expression of inflammatory genes and the infiltration of CD8+ T cells into tumor sites. Deletion of Irg1 in mice suppresses the growth of multiple tumor types and enhances the efficacy of anti-PD-(L)1 immunotherapy. Our study provides a proof of concept that ACOD1 is a potential target for immune-oncology drugs and IRG1-deficient macrophages represent a potent cell therapy strategy for cancer treatment even in pancreatic tumors that are resistant to T cell-based immunotherapy.

[Sequencing Analysis of miRNAs in Brain-Derived Exosomes of Adolescent Mice With Depression-Like Behaviors].

Objective: To explore the differential expression of microRNAs (miRNAs) in brain-derived exosomes (BDEs) of adolescent mice with depression-like behavior. Methods: The experimental group consisted of susceptible adolescent mice exposed to chronic social defeat stress (CSDS), and sucrose preference test (SPT) and open field test (OFT) were performed to evaluate their depression-like behaviors. BDEs were extracted by ultracentrifugation (UC). The morphology, particle size, and surface marker proteins of BDEs were examined by transmission electron microscopy, nano-flow cytometry and Western blot. The expression of miRNA in BDEs was evaluated by high-throughput RNA sequencing. GO enrichment analysis and KEGG pathway enrichment analysis were carried out based on bioinformatics. Results: The particle size of BDEs ranged between 50 to 100 nm and they displayed a typical disc-shaped vesicle structure. TSG101 and syntenin, the exosome-positive proteins, were detected. In the BDEs of mice with depression-like behaviors induced by CSDS, 13 miRNAs were significantly upregulated and 4 miRNAs were significantly downregulated. Go and KEGG analysis showed that differentially expressed miRNAs were significantly enriched in PI3K-Akt signaling pathway, axonal guidance, and hypoxic response. Conclusion: It was found in this study that exosomal miRNAs in brain tissue might be involved in such biological processes as insulin resistance, neuroplasticity, and hypoxic response, thereby regulating brain functions and causing depression-like behaviors.

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds.

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

Integrated identification of key immune related genes and patterns of immune infiltration in calcified aortic valvular disease: A network based meta-analysis.

Background: As the most prevalent valvular heart disease, calcific aortic valve disease (CAVD) has become a primary cause of aortic valve stenosis and insufficiency. We aim to illustrate the roles of immune related genes (IRGs) and immune cells infiltration in the occurrence of CAVD. Methods: Integrative meta-analysis of expression data (INMEX) was adopted to incorporate multiple gene expression datasets of CAVD from Gene Expression Omnibus (GEO) database. By matching the differentially expressed genes (DEGs) to IRGs from "ImmPort" database, differentially expressed immune related genes (DEIRGs) were screened out. We performed enrichment analysis and found that DEIRGs in CAVD were closely related to inflammatory response and immune cells infiltration. We also constructed protein-protein interaction (PPI) network of DEIRGs and identified 5 key DEIRGs in CAVD according to the mixed character calculation results. Moreover, CIBERSORT algorithm was used to explore the profile of infiltrating immune cells in CAVD. Based on Spearman's rank correlation method, correlation analysis between key DEIRGs and infiltrating immune cells was performed. Results: A total of 220 DEIRGs were identified and the enrichment analysis of DEIRGs showed that they were significantly enriched in inflammatory responses. PPI network was constructed and PTPN11, GRB2, SYK, PTPN6 and SHC1 were identified as key DEIRGs. Compared with normal aortic valve tissue samples, the proportion of neutrophils, T cells CD4 memory activated and macrophages M0 was elevated in calcified aortic valves tissue samples, as well as reduced infiltration of macrophages M2 and NK cells activated. Furthermore, key DEIRGs identified in the present study, including PTPN11, GRB2, PTPN6, SYK, and SHC1, were all significantly correlated with infiltration of various immune cells. Conclusion: This meta-analysis suggested that PTPN11, GRB2, PTPN6, SYK, and SHC1 might be key DEIRGs associated with immune cells infiltration, which play a pivotal role in pathogenesis of CAVD.

Epigenetic regulation of cutaneous T-cell lymphoma is mediated by dysregulated lncRNA MALAT1 through modulation of tumor microenvironment.

Cutaneous T-Cell Lymphoma (CTCL) is a rare non-Hodgkin lymphoma marked by migration of T-lymphocytes to the skin. It has many subtypes some of which are aggressive with documented metastasis. We investigated a possible role of lncRNA MALAT1 in CTCL cells because of its documented involvement in cancer metastasis. A screening of MALAT1 in CTCL patients revealed its elevated levels in the patients, compared to healthy individuals. For our investigation, we employed HH and H9 CTCL cells and silenced MALAT1 to understand the MALAT1 mediated functions. Such silencing of MALAT1 resulted in reversal of EMT and inhibition of cancer stem cell phenotype, along with reduced cell growth and proliferation. EMT reversal was established through increased E-cadherin and reduced N-cadherin while inhibition of cancer stem cell phenotype was evident through reduced Sox2 and Nanog. CTCL patients had higher circulating levels of IL-6, IL-8, IL-10, TGFß, PGE2 and MMP7 which are factors released by tumor-associated macrophages in tumor microenvironment. MALAT1 sponged miR-124 as this tumor suppressive miRNA was de-repressed upon MALAT1 silencing. Moreover, downregulation of miR-124 attenuated MALAT1 silencing effects. Our study provides a rationale for further studies focused on an evaluation of MALAT1-miR-124 in CTCL progression.

[Spatial structure characteristics of plain ecological plantation in Tongzhou District, Beijing, China]. / 北京通州平原生态林空间结构特征.

Forest spatial structure (FSS) directly reflects resource competition and growth space distribution among different trees. The characteristics of FSS play an important role in mastering the growth status of ecological forest, formulating stand structure regulation measures, and improving forest quality and ecological services. In this study, seven plain ecological plantations including Pinus tabuliformis, Fraxinus chinensis, Salix matsudana, Populus tomentosa, Sophora japonica, Robinia pseudoacacia, and Salix babylonica in Tongzhou District, Beijing were selected as the research objects. The spatial structure characteristics of plain ecological plantations were evaluated by aggregation degree, angle index, neighborhood comparison, open degree, canopy index, competition index, edge benefit, and spatial structure comprehensive index. The horizontal distribution pattern of stand was well, with the aggregation degree of 0.32-1.41, the angle index of 0.4, and the neighborhood comparison mainly around 0.5. The vertical distribution pattern of stand was not well and needed to be improved, with the open degree of 0.19-0.52, most canopy indexes of about 0.7. The competition index presented a high competitive status with the all values of >50. Except the comprehensive evaluation index of R. pseudoacacia plantation presented in grade Ⅲ, the other six kinds of plain ecological plantations fell to grade Ⅱ, with low stand openness and low vitality. The comprehensive evaluation indices of FSS followed the order of R. pseudoacacia > S. babylonica > P. tabuliformis > S. matsudana > F. chinensis > S. japonica > P. tomentosa.

Rhodium-Catalyzed Regioselective Hydroformylation of Alkynes to α,ß-Unsaturated Aldehydes Using Formic Acid.

A rhodium-catalyzed hydroformylation of alkynes with formic acid was developed. The method provides α,ß-unsaturated aldehydes in high yield and E-selectivity without the need to handle toxic CO gas.

Light-Induced Nanowetting: Erasable and Rewritable Polymer Nanoarrays via Solid-to-Liquid Transitions.

Template wetting methods have been widely applied in the preparation of one-dimensional (1D) polymer nanomaterials. The pattern control using the template wetting methods, however, still remains a great challenge, mainly due to the nonselectivity of the polymers toward the environmental triggering. In this work, we present a facile light-induced nanowetting (LIN) method to fabricate patterned nanoarrays using anodic aluminum oxide (AAO) templates. Photoresponsive azobenzene-containing polymers (azopolymers) that exhibit light-induced reversible solid-to-liquid transitions are used. Upon exposure to ultraviolet lights, the azopolymer chains can wet the nanopores of the AAO templates in a liquid state via capillary force. The azopolymer chains are then solidified by illuminating them with visible lights, resulting in the formation of azopolymer nanoarrays. Notably, using designed photomasks, the patterns of the nanoarrays can be ingeniously controlled with the characteristic of erasable and rewritable nanostructures.

Designing an anamorphic illumination system with an RTIR prism for a tilt-and-roll-pixel-type projector.

A relay lens system design for a mini-projector with telecentric illumination is described. The reverse total internal reflection (RTIR) prism for angular magnification and lateral magnification is discussed in detail, and magnifications under different digital micromirror devices (DMD) are compared. The tilt-and-roll pixel (TRP) DMD chip (tilt angle is ${\pm 17}^\circ $±17∘) is the latest spatial light modulator, and the f-number of the illumination system is 1.71. Using the TRP DMD, the lateral magnification and the angular magnification for the RTIR prism can be increased by 3.77% and 8.73% over that obtainable using the conventional DMD chip (tilt angle is ${\pm 12}^\circ $±12∘). In order to solve for the angular magnification of an RTIR prism, the baffle is set at the aperture stop of the relay lens system. There is a trade-off between the efficiency and the contrast ratio with the baffle. When B (the position of the baffle) is at 0.11, the contrast ratio of the illumination system is 7590:1 and the efficiency is 57%. The spot size at the edge and corner of the DMD active area is controlled to be less than 250 µm, and the optical distortion is less than 1%.

From Ancient Medicine to Targeted Nanocarrier: A Sparganii Rhizoma-Derived Nanoparticle for Diagnostic Imaging and Endocrine Therapy in Cancer.

The traditional Chinese medicine Sparganii Rhizoma has a long history in the treatment of gynecological diseases. In our previous work, we found that an extract of Sparganii Rhizoma had antitumor activity, attributed to the aluminum-rich polysaccharide, "SpaTA", which we isolated. SpaTA can selectively regulate the estrogen receptor, but its mechanism of antitumor activity is poorly understood. In the present study, we found that SpaTA naturally exists as a nanoparticle with a regular physical morphology. SpaTA induced apoptosis in human breast cancer cells mainly through interaction with estrogen receptors, ERα and GPR30, followed by activation of the PI3K/Akt and MEK/ERK pathways. Notably, cells also adjusted their cytoskeletal plasticity in response to SpaTA, which inhibited cell motility by suppressing focal adhesion and cytoskeleton reorganization via FAK. On the basis of these antitumor effects, we further modified SpaTA by conjugating it with the near-infrared dye, ICG, and loading the particles with the TGFß inhibitor, LY2157299, to form the tumor-targeting nanomedicine, "SpaTAX". The application of SpaTAX to breast cancer models enables a dual use regimen: a single dose for fluorescence imaging of the tumor site, where SpaTAX accumulates due to the enhanced permeability and retention effect, and a multidose for antitumor treatment through estrogen receptor- and TGFß-related signaling pathways. The synergetic roles of estrogen receptors and TGFß pathways are responsible for SpaTAX-induced reinforced suppression on tumor growth. Finally, we assessed the biosafety of the formulation and found that SpaTAX is highly tolerable and may therefore be considered safe for future clinical theranostic application. Altogether, our results demonstrated a superior tumor targeting ability of SpaTA both in diagnostic imaging and endocrine therapy and also proved SpaTA as a promising nanocarrier with a high therapeutic capacity and a favorable modification potential.

Management and outcomes of pregnant patients with central nervous system hemangioblastoma.

The study aims to assess the management and maternal and fetal outcomes of pregnancies complicated by central nervous system (CNS) hemangioblastoma. Twenty-four female patients with CNS hemangioblastoma, who were pregnant in a tumor-burden status, were identified. Their medical charts, treatments, and follow-up materials were carefully reviewed. Of the included 24 CNS patients with hemangioblastoma (14 intracranial and 10 spinal hemangioblastomas), 5 patients (20.8%) were diagnosed with Von Hippel-Lindau disease (VHL). The median age of these patients at admission was 27.5 years. Intracranial hypertension was a common presenting symptom for patients with intracranial hemangioblastoma and was observed in 85.7% (12/14) of cases; the other 10 patients with spinal hemangioblastomas all suffered from paresthesia. Overall, 66.7% (16/24) of patients with CNS hemangioblastoma went through the gestational course with conventional observation; 16.6% (4/24) of patients accepted a ventriculo-peritoneal shunt (VPS) to delay the tumor resection; and 16.7% (4/24) of patients needed urgent tumor resection even when symptomatic treatments were given. Variable symptom improvement was seen when patients had follow-up visits at a median of 32.5 months. No maternal death or tumor recurrence was identified. For the fetal prognoses, one (4.2%) pregnancy ended in a spontaneous miscarriage and for (16.7%) pregnancies were interrupted; the other 19 (79.2%) live births were in good status without any congenital malformations. Symptomatic treatment was the first choice for pregnant patients with CNS hemangioblastoma. When needed, urgent tumor resection could be safely achieved with careful maternal and fetal monitoring. Both maternal and fetal prognoses were favorable during follow-up.

Comparison of Antibacterial Adhesion When Salivary Pellicle Is Coated on Both Poly(2-hydroxyethyl-methacrylate)- and Polyethylene-glycol-methacrylate-grafted Poly(methyl methacrylate).

Although poly(2-hydroxyethyl methacrylate) (pHEMA) and polyethylene glycol methacrylate (PEGMA) have been demonstrated to inhibit bacterial adhesion, no study has compared antibacterial adhesion when salivary pellicle is coated on polymethyl methacrylate (PMMA) grafted with pHEMA and on PMMA grafted with PEGMA. In this study, PMMA discs were fabricated from a commercial orthodontic acrylic resin system (Ortho-Jet). Attenuated total reflection-Fourier transform infrared spectra taken before and after grafting confirmed that pHEMA and PEGMA were successfully grafted on PMMA. Contact angle measurements revealed PMMA-pHEMA to be the most hydrophilic, followed by PMMA-PEGMA, and then by PMMA. Zeta potential analysis revealed the most negative surface charges on PMMA-PEGMA, followed by PMMA-pHEMA, and then by PMMA. Confocal laser scanning microscopy showed green fluorescence in the background, indicating images that influenced the accuracy of the quantification of live bacteria. Both the optical density value measured at 600 nm and single plate-serial dilution spotting showed that pHEMA was more effective than PEGMA against Escherichia coli and Streptococcus mutans, although the difference was not significant. Therefore, the grafting of pHEMA and PEGMA separately on PMMA is effective against bacterial adhesion, even after the grafted PMMA were coated with salivary pellicle. Surface hydrophilicity, bactericidality, and Coulomb repulsion between the negatively charged bacteria and the grafted surface contributed to the effectiveness.

SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer.

Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl-CoA oxidase 1) is the first and rate-limiting enzyme in fatty acid ß-oxidation and a major producer of H2O2 ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5-mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome-induced oxidative stress, in liver protection, and in suppressing HCC development.

Phylogenetic and temporal dynamics of human immunodeficiency virus type 1 CRF01_AE and CRF07_BC among recently infected antiretroviral therapy-naïve men who have sex with men in Jiangsu province, China, 2012 to 2015: A molecular epidemiology-based study.

The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic.The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01_AE and CRF07_BC among antiretroviral therapy (ART)-naïve MSM recently infected with HIV-1 in Jiangsu Province.We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015. We collected information on demographics and sexual behaviors and a blood sample for HIV genome RNA extraction, RT-PCR amplification, and DNA sequencing. Multiple alignments were made using Gene Cutter, with the selected reference sequences of various subtypes/recombinants from the Los Alamos HIV-1 database. Phylogenetic and Bayesian evolutionary analysis was performed by MEGA version 6.0, Fasttree v2.1.7. and BEAST v1.6.2. Categorical variables were analyzed using χ test (or Fisher exact test where necessary). χ test with trend was used to assess the evolution of HIV-1 subtype distribution over time. All data were analyzed using SPSS20.0 software package (IBM Company, New York, NY).HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (60.06%), CRF07_BC (22.29%), subtype B (5.88%), CRF67_01B (5.26%), CRF68_01B (2.79%), CRF55_01B (1.55%), CRF59_01B (0.93%), and CRF08_BC (0.62%). Two unique recombination forms (URFs) (0.62%) were also detected. Four epidemic clusters and 1 major cluster in CRF01_AE and CRF07_BC were identified. The introduction of CRF01_AE strain (2001) was earlier than CRF07_BC strain (2004) into MSM resided in Jiangsu based on the time of the most recent common ancestor.Our study demonstrated HIV-1 subtype diversity among ART-naïve MSM recently infected with HIV-1 in Jiangsu. We first depicted the spatiotemporal dynamics, traced the dates of origin for the HIV-1 CRF01_AE/07_BC strains and made inference for the effective population size among newly infected ART-naïve MSM in Jiangsu from 2012 to 2015. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster would be of great value to the monitoring of the epidemic and control of transmission, improvement of antiretroviral therapy strategies, and design of vaccines.