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A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health. [ABSTRACT FROM AUTHOR]

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery. [Display omitted] • Icariin reacts with phospholipid to form phospholipid complex with self-assembly ability. • Icariin-phospholipid complex (IPC) is stable during autoclaving and nebulization processes. • IPC sustains drug release, enhances lung affinity and slows lung clearance. • Intratracheal delivery of IPC improves and extends drug exposure to lung tissues and immune cells in lungs. • Instilled IPC prolongs pulmonary anti-inflammatory effects and increases the survival rate of mice with ARDS. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks (MOFs) with abundant active sites, a class of materials composed of metal nodes and organic ligands, is widely used for photocatalytic degradation of pollutants. However, the rapid recombination of photoinduced carriers of MOFs limits its photocatalytic degradation performance. Herein, Ti3C2Tx nanosheets‐based NH2‐MIL‐101(Fe) hybrids with Schottky‐heterojunctions were fabricated by in situ hydrothermal assembly for improved photocatalytic activity. The photodegradation efficiencies of the NH2‐MIL‐101(Fe)/Ti3C2Tx (N‐M/T) hybrids for phenol and chlorophenol were 96.36 % and 99.83 % within 60 minutes, respectively. The N‐M/T Schottky‐heterojunction duly transferred electrons to the Ti3C2Tx nanosheets surface via built‐in electric fields, effectively suppressing the recombination of photogenerated carriers, thereby improving the photocatalytic performance of NH2‐MIL‐101(Fe). Moreover, the Fe‐mixed‐valence in the N‐M/T led to improvement in the efficiency of the in situ generated photo‐Fenton reactions, further enhancing the photocatalytic activity with more generated reactive oxygen species (ROS). The study proposes a highly effective removal of phenolic pollutants in wastewater. [ABSTRACT FROM AUTHOR]

[Display omitted] The slow conversion of Fe(Ⅱ)/Fe(III) cycle was largely limited the degradation efficiency of many photo-Fenton systems. Herein, four Fe-MOFs nanorods (namely Fe-TCPP-1, Fe-TCPP-2, Fe-TCPP-3, Fe-TCPP-4) with decreasing length-diameter ratios were synthesized in a household microwave oven, using photosensitizer porphyrin and iron ions with Fenton activity as building blocks. Among them, the Fe-TCPP-3 exhibited high photogenerated electron-hole (e −- h +) separation efficiency and largest pore structure, endowing Fe-TCPP-3 with superior photo-Fenton property. In addition, Fe-TCPP-3 based photo-Fenton system was applied to efficiently degrade antibiotic ciprofloxacin (CIP) under neutral condition, due to the continuously generated reactive species (h +, e −, OH·, O 2 ·–, 1O 2) in Fe-TCPP-3 under visible-light irradiation. With irradiation for 30 min, the degradation efficiency of the system could reach about 73 %, which was about 26-fold towards the system without light irradiation. This study paved a way to modulating the photo-Fenton activity of MOF-based catalysts. [ABSTRACT FROM AUTHOR]

Drug repurposing is of interest for therapeutics innovation in many human diseases including coronavirus disease 2019 (COVID-19). Methodological innovations in drug repurposing are currently being empowered by convergence of omics systems science and digital transformation of life sciences. This expert review article offers a systematic summary of the application of artificial intelligence (AI), particularly machine learning (ML), to drug repurposing and classifies and introduces the common clustering, dimensionality reduction, and other methods. We highlight, as a present-day high-profile example, the involvement of AI/ML-based drug discovery in the COVID-19 pandemic and discuss the collection and sharing of diverse data types, and the possible futures awaiting drug repurposing in an era of AI/ML and digital technologies. The article provides new insights on convergence of multi-omics and AI-based drug repurposing. We conclude with reflections on the various pathways to expedite innovation in drug development through drug repurposing for prompt responses to the current COVID-19 pandemic and future ecological crises in the 21st century. [ABSTRACT FROM AUTHOR]

Drug repurposing has broad importance in planetary health for therapeutics innovation in infectious diseases as well as common or rare chronic human diseases. Drug repurposing has also proved important to develop interventions against the COVID-19 pandemic. We propose a new approach for drug repurposing involving two-stage prediction and machine learning. First, diseases are clustered by gene expression on the premise that similar patterns of altered gene expression imply critical pathways shared in different disease conditions. Next, drug efficacy is assessed by the reversibility of abnormal gene expression, and results are clustered to identify repurposing targets. To cluster similar diseases, gene expression data from 262 cases of 31 diseases and 268 controls were analyzed by Uniform Manifold Approximation and Projection for Dimension Reduction followed by k-means to optimize the number of clusters. For evaluation, we examined disease-specific gene expression data for inclusion, body myositis, polymyositis, and dermatomyositis (DM), and used LINCS L1000 characteristic direction signatures search engine (L1000CDS2) to obtain lists of small-molecule compounds that reversed the expression patterns of these specifically altered genes as candidates for drug repurposing. Finally, the functions of affected genes were analyzed by Gene Set Enrichment Analysis to examine consistency with expected drug efficacy. Consequently, we found disease-specific gene expression, and importantly, identified 20 drugs such as BMS-387032, phorbol-12-myristate-13-acetate, mitoxantrone, alvocidib, and vorinostat as candidates for repurposing. These were previously noted to be effective against two of the three diseases, and have a high probability of being effective against the other. That is, inclusion body myositis and DM. The two-stage prediction approach to drug repurposing presented here offers innovation to inform future drug discovery and clinical trials in a variety of human diseases. [ABSTRACT FROM AUTHOR]

Based on the laccase-mimicking activity of Cu2+-modified University of Oslo (UiO) metal–organic framework (UiO-67-Cu2+), we developed a colorimetric sensor array for distinguishing a series of phenols with different number and position of substituted hydroxyl group (-OH) and different substituent group on the benzene ring, including phenol, catechol, quinol, resorcinol, pyrogallol, phloroglucinol, o-chlorophenol, o-aminophenol, and o-nitrophenol. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of phenolic compounds were obtained by theoretical calculation. The results show that the lower the LUMO energy level, the easier the chromogenic reaction occurs. The UiO-67-Cu2+-catalyzed phenol chromogenic reaction showed a good linearity in the range from 0.1 to 200 μM with limit of detection approximately 61 nM. Through the detection of phenol in tap water and river water, the recovery rate and RSD (n = 3) were calculated as 94.1~103% and 1.0~3.3, respectively, showing good recovery, reliable results, and outstanding stability. Therefore, the proposed colorimetric sensor array will have a great potential for the detection of phenols in the environment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ag-MnCo 2 O 4 heterogeneous interfaces was constructed through a simple strategy. • The Ag-O-M channels induced charge redistribution to optimize the adsorption energy of oxygen intermediate. • The assembled ZABs with Ag-MCO/NCNTs as cathode exhibited a favorable cycling performance. Physical structure change of catalysts based on the electronic metal-support interaction (EMSI) effects is a prospective strategy to regulate the surface electronic structure of catalysts and further enhance their catalytic performance. To optimize the constrained intrinsic oxygen evolution reaction/oxygen reduction reaction (OER/ORR) activity of spinel MnCo 2 O 4 , we present a facile hydrothermal and photoreduction strategy to synthesize the Ag and MnCo 2 O 4 supported on N-doped carbon nanotubes (Ag-MnCoO/NCNTs) with the EMSI effect. Ag-MnCoO/NCNTs as catalyst shows enhanced performance for OER (overpotential of 340 mV) and ORR (half-wave potential of 0.80 V). Furthermore, a zinc-air battery is assembled based on Ag-MnCoO/NCNTs cathode, which affords an open circuit potential of 1.49 V and favorable cycling performance for 200 h. Theoretical calculations illustrate the introduction of Ag reduces the charge density of the tetrahedral Co site along the direction of the dangling bonds and optimizes the adsorption of oxygen intermediates on tetrahedral Co, thus lowering the reaction activation energy and improving its oxygen catalytic activity. This work provides new insights to guide the fabrication of advanced oxygen electrocatalysts. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are of environmental concern due to their bioavailability and potential impacts on a wide range of marine biota. In this study, we investigated the ingestion, bioaccumulation and egestion of fluorescent polystyrene (PS) micospheres (10 μm) in both larvae and adults of marine medaka (Oryzias melastigma), with or without food supply. The post-exposure effects of non-fluorescent PS (10 μm) on the survival, growth and reproduction of medaka larvae were also explored. Results showed that the PS microspheres could be ingested by both larvae and adults during the 48 h-exposure. Notably, feeding status was found to significantly affect the ingestion in medaka adults, which was not observed in the larvae. The egestion process of PS was rapid during the first recovery day but there was still certain percent of particles retained in digestive tracts at the end of 7 d recovery for either larvae or adults. After a 14 d pre-exposure with the non-fluorescent PS microspheres, the subsequent survival, growth and reproduction of medaka larvae were all significantly affected at the end of 120 d of experiment without PS. Overall, these results indicate that fishes might ingest or retain more MPs if the environmental abundance of MPs continues to increase while the available food decreases. Medaka fishes in larval stage have no capacity to select natural food sources like the adults. The chronic and "legacy effect" of MPs might also be a problem worthy paid more attention in future research instead of acute and immediate effect studies. • Marine medaka larvae and adults can ingest and egest microplastics (MPs). • Feeding status was found to significantly affect the ingestion in medaka adults. • Larvae had no capacity to select food sources like the adults. • Increased mortality, decreased growth and reproduction were observed after exposure. • The chronic and legacy effect of MPs should be paid more attention in future. [ABSTRACT FROM AUTHOR]

The negative effects of metal oxide nanoparticles on aquatic environment and organisms have caused much concern. In this study, the embryotoxicity of zinc oxide nanoparticles (ZnO NP) to marine medaka, Oryzias melastigma , was explored and compared with that of aqueous Zn (ZnSO 4 ·7H 2 O). The Zn 2+ released from ZnO NP in artificial seawater at exposure concentrations was also measured. Results showed that zinc ion release percentage (%) decreased with increasing concentration, which was 44%, 41% and 25% at 0.1, 1 and 10 mg/L of ZnO NP suspension, respectively. After 20 d exposure of medaka embryos to ZnO NP, we observed increased mortality and heart rate, reduced percent total hatching success, delayed hatching of embryos and increased malformation% of newly-hatched larvae in ZnO NP treatment compared to the control group. Furthermore, ZnO NPs have significantly greater effects than the aqueous Zn for mortality and heart rate, indicating that ZnO NPs themselves, in particulate or aggregate form, contribute to the observed toxicity. Edema was the most commonly found malformation in newly-hatched larvae after ZnO NP exposure. Overall, our findings suggest that the embryonic stage of marine medaka is sensitive to ZnO NP exposure. Studies of the toxic mechanism of ZnO NPs should not ignore the impact of NPs since the greater effects of ZnO NPs than of aqueous Zn ions observed in this study cannot be explained by the ZnO NP dissolution. The ion release profile of ZnO NPs in marine environment is related to both NP and seawater characteristics, which should be analyzed on a case-by-case basis. The ZnO NP-related Zn speciation may play an important role in the dissolution and toxicity processes of ZnO NPs in marine environment, and further speciation study may contribute to the interpretation of ZnO NP toxicity. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell-mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (Tregs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Tregs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in Tregs and restore the ability of conventional CD4+ T cells to upregulate Foxp3 and generate peripherally derived Tregs. Moreover, we demonstrate that suppression mediated by Tregs from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction-mediated intercellular communication as an important component of the Tregs suppression mechanism compromised in NOD mice and suggests how Tregs mediated immune regulation can be improved. [ABSTRACT FROM AUTHOR]

In this study, the toxicities of sediment-associated silver added to sediment as commercially available silver nanoparticles (Ag NPs, 20 and 80 nm) and aqueous Ag (AgNO 3 ) to the estuarine polychaete, Nereis (Hediste) diversicolor , were investigated for both individual and subcellular endpoints after 10 d of exposure. Both Ag NP types were characterized in parallel to the toxicity studies and found to be polydispersed and overlapping in size. Burrowing activity decreased (marginally) with increasing Ag concentration and depended on the form of Ag added to sediment. All worms accumulated Ag regardless of the form in which it was added to the sediment, and worm size (expressed as dry weight) was found to significantly affect bioaccumulation such that smaller worms accumulated more Ag per body weight than larger worms. Lysosomal membrane permeability (neutral red retention time, NRRT) and DNA damage (comet assay tail moment and tail DNA intensity %) of Nereis coelomocytes increased in a concentration-dependent manner in all three Ag treatments. Ag NP treatments were more toxic than aqueous Ag for all toxicity endpoints, even though bioaccumulation did not differ significantly among Ag forms. No significant difference in toxicity was observed between the two Ag NP treatments which was attributed to their overlap in particle size. [ABSTRACT FROM AUTHOR]

Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharornyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy. We further identified the autophagy signaling component Atg3 as a substrate for Esa1. Specifically, acetylation of K19 and K48 of Atg3 regulated autophagy by controlling Atg3 and Atg8 interaction and lipidation of AtgS. Starvation induced transient K19-K48 acetylation through spatial and temporal regulation of the localization of acetylase Esa1 and the deacetylase Rpd3 on pre-autophagosomal structures (PASs) and their interaction with Atg3. Attenuation of K19-K48 acetylation was associated with attenuation of autophagy. Increased K19-K48 acetylation after deletion of the deacetylase Rpd3 caused increased autophagy. Thus, protein acetylation contributes to control of autophagy. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing concern about the toxicities and potential risks, both still poorly understood, of silver nanoparticles for the aquatic environment after their eventual release via wastewater discharges. In this study, the toxicities of sediment associated nano (<100nm)-, micron (2–3.5μm)- and ionic (AgNO3)-Ag on the sediment-dwelling polychaete, Nereis diversicolor, were compared after 10 days of sediment exposure, using survival, DNA damage (comet assay) and bioaccumulation as endpoints. The nominal concentrations used in all exposure scenarios were 0, 1, 5, 10, 25, and 50μgAg/g dry weight (dw) sediment. Our results showed that Ag was able to cause DNA damage in Nereis coelomocytes, and that this effect was both concentration- and Ag form-related. There was significantly greater genotoxicity (higher tail moment and tail DNA intensities) at 25 and 50μg/gdw in nano- and micron-Ag treatments and at 50μg/gdw in the ionic-Ag treatment compared to the controls (0μg/gdw). The nano-Ag treatment had the greatest genotoxic effect of the three tested Ag forms, and the ionic-Ag treatment was the least genotoxic. N. diversicolor did accumulate sediment-associated Ag from all three forms. Ag body burdens at the highest exposure concentration were 8.56±6.63, 6.92±5.86 and 9.86±4.94μg/gdw for worms in nano-, micron- and ionic-Ag treatments, respectively, but there was no significant difference in Ag bioaccumulation among the three treatments. [Copyright &y& Elsevier]

The aim of our study was to describe and compare nutritional status and food related behaviours in rural pregnant women of Li ethnicity as they had been divided into mountainous and costal groups by residential area. One hundred and ninety-six randomly selected healthy rural pregnant women of Li ethnicity for the mountainous group (MG), and eighty-two for the coastal group (CG) were recruited. Data were collected via demographic questionnaires, anthropometric measurements, food related behaviour questionnaires, five day dietary diaries and plasma folate tests. The mean (SD) age, years of education, and height of all participants were respectively 25.7 (3.99) years, 7.57 (2.45) years and 155 (5.04) cm, without significant group differences (p>0.05). Significant differences were shown in dietary intakes of protein, fat, carbohydrate, dietary fibre, thiantine, vitamin C, folate, potassium, sodium and magnesium between MG and CG (p<0.05). The prevalence of plasma folate deficiency differed significantly between groups (3.08% in MG vs 37.8% in CG, p<0.001). High prevalence of active or passive smoking (65.1% in MG vs 68.4% in CG), alcohol consumption (13.8% in MG vs 2.6% in CG), and betel quid chewing (19.6% in MG vs 53.9% in CG) were found in all participants. Differences in alcohol consumption and betel quid chewing rates between groups were also significant (p<0.05). In general, coastal Li pregnant women have a poorer plane of nutrition than their mountainous counterparts. Therefore, healthy diet and lifestyle education are urgently required and should be emphasised during routine prenatal care. [ABSTRACT FROM AUTHOR]

Abstract: N-n-Butyl haloperidol iodide (F2), a novel compound derived from haloperidol, protects against the damaging effects of ischemia/reperfusion (I/R) injury in vitro and in vivo. We tested whether the myocardial protection of F2 on cardiomyocyte hypoxia/reoxygenation (H/R) injury is mediated by modulating protein kinase C (PKC) activity in primary cultured cardiomyocytes. Primary cultures of ventricular cardiomyocytes underwent 2-h hypoxia and 30-min reoxygenation. Total PKC activity was measured, and the translocation pattern of PKCα, βII, δ and ɛ isoforms was assessed by fractionated western blot analysis. We investigated the association of PKC isoform translocation and H/R-induced injury in the presence and absence of the specific inhibitors and activator. Measurements included cell damage evaluated by creatine kinase (CK) release, and apoptosis measured by annexin V-FITC assay. In primary cultured cardiomyocytes exposed to H/R, PKCα, δ and ɛ were translocated, with no change in PKCβII activity. Total PKC activity, CK release and apoptosis were increased after H/R. Treatment with the conventional PKC inhibitor Gő6976 reduced early growth response-1 (Egr-1) protein expression and attenuated apoptosis. The PKCɛ inhibitor peptide ɛV1–2 increased H/R injury without influencing Egr-1 expression. Pretreatment with F2 inhibited translocation of PKCα, increased translocation of PKCɛ, and relieved the CK release and apoptosis. The protection of F2 was blocked in part by the conventional PKC activator thymeleatoxin (TXA) and ɛV1–2 peptide. F2 significantly alleviated H/R-induced injury, which might be attributed to the combined benefits of inhibiting PKCα and activating PKCɛ. [Copyright &y& Elsevier]

Nephrotoxicity is the major limiting factor for the use of cisplatin in cancer therapy. Recent studies have demonstrated an important role for p53 in cisplatin-induced renal injury. Nevertheless, pharmacological and genetic blockade of p53 only provides partial renoprotective effects, suggesting the presence of p53-independent injury mechanisms. To understand the p53-independent mechanisms, we have now examined cisplatin-induced apoptosis in p53-deficient kidney cells. We show that cisplatin could induce Bax activation, cytochrome c release, and apoptosis in primary cultures of p53-deficient renal tubular cells, albeit at a level that was lower than in the wild-type cells. Cisplatin could also induce typical apoptosis in p53-deficient baby mouse kidney (BMK) cells. The apoptosis was caspase dependent and could be completely blocked by general caspase inhibitors. Bax and Bak, two key molecules in the mitochondrial pathway of apoptosis, were interdependently activated by cisplatin, with Bax translocation to and Bax/Bak oligomerization in mitochondria, leading to cytochrome c release. Importantly, cytochrome c release and apoptosis were diminished in Bax/Bak single or double-knockout BMK cells. Furthermore, overexpression of Bcl-2 could ameliorate cisplatin-induced cytochrome c release and apoptosis. Together, the results have demonstrated a p53-independent mechanism of cisplatin nephrotoxicity that involves the mitochondrial pathway of apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we have demonstrated evidence suggesting that SUMO4 negatively regulates NFκB transcriptional activity, probably through sumoylation of IκBα. Here, we present data indicating that SUMO4 possesses the capacity to conjugate to IκBα. Luciferase reporter assays in 3T3 cells deficient for IκBα further demonstrated that SUMO4 regulates NFκB signaling dependent on its sumoylation of IκBα. More importantly, a putative NFκB binding motif has been characterized within the SUMO4 promoter. Subsequent promoter reporter assays revealed that SUMO4 promoter with disrupted NFκB binding motif failed to response to NFκB specific IL-1β stimulation. ChIP assays showed that NFκB binds to SUMO4 promoter and activates its transcription. Together, our data suggest that SUMO4 may act as a negative feedback regulator to prevent excessive activation of NFκB. Given the importance of NFκB signaling in immune response, SUMO4 could play a role to tightly control the potency of immune response to prevent autoimmunity. [Copyright &y& Elsevier]

Abstract: For the mechanism of production of γ-ray bursts (GRBs) it is rather generally recognized that the long-term γ-ray burst (LGRB) originates from the deaths of massive stars while the short-term γ-ray burst (SGRB) originates from the merging of close binaries. Therefore the speculation naturally follows that the number of LGRBs is directly proportional to the star formation rate (SFR). However, it is indicated from recent data analyses that this speculation does not fit the observations very well. It is considered that only massive stars with masses greater than a certain critical mass can produce the LGRB, so the initial mass function (IMF) of stars can significantly affect the production rate of LGRBs. In this paper it is considered that the IMF of stars can be used to explain the observed number distribution of the LGRBs with the redshift, and this has led to some good results. [Copyright &y& Elsevier]

Spores of Laminaria japonica were cryopreserved in liquid nitrogen. Dimethyl sulphoxide was found to be the most effective and least toxic cryoprotectant for cryopreservation of spores of L. japonica. By comparing the post-thaw viability of cryopreserved spores, rapid or gradual cooling procedures were found to be suitable means to cool spores. Following a process of gradual cooling, 24 h storing in liquid nitrogen and quick thawing, 50% of cryopreserved spores remained viable. Such spores developed into gametophytes, which retained the potential to form gametophyte clones or to give rise to sporophytes. Significantly greater numbers of male gametophytes than female gametophytes were observed to develop from thawed spores. The cryopreservation of spores of L. japonica is not only simple to perform but permits the cryopreservation of many strains with minimal requirements of both labour and space. [ABSTRACT FROM AUTHOR]

Genomewide linkage analyses since the early 1990s suggested over 20 genomic intervals that may contain susceptibility genes for type 1 diabetes. However, the identification of the specific genes in these intervals presents a formidable challenge due to a number of difficulties associated with genetic mapping and cloning of genes implicated in complex diseases. One of the difficulties is due to the presence of many weak and different susceptibility genes in different patients and populations, a phenomenon known as genetic heterogeneity. In 2004, we reported the cloning of a novel small ubiquitin-like modifier ( SUMO) gene, SUMO4, in the IDDM5 interval on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 is a susceptibility gene for type 1 diabetes mellitus (T1DM). In this article, we will summarize genetic association data suggesting that SUMO4 is consistently associated with T1DM in the Asian populations while the association is more heterogeneous in the Caucasian populations. We will also discuss the possible molecular pathways through which sumoylation may regulate T1DM and autoimmunity. [ABSTRACT FROM AUTHOR]

Background: We have recently cloned and characterized a novel gene family named ancient conserved domain protein (ACDP) in humans. To facilitate the functional study of this novel gene family, we have cloned and characterized Acdp, the mouse homologue of the human ACDP gene family. Results: The four Acdp genes (Acdp1, Acdp2, Acdp3 and Acdp4) contain 3,631 bp, 3,244 bp, 2,684 bp and 2,743 bp of cDNA sequences, and encode deduced proteins of 951, 874, 713 and 771 amino acids, respectively. The mouse Acdp genes showed very strong homologies (>90%) in both nucleotide and amino acid sequences to their human counterparts. In addition, both nucleotide and amino acid sequences within the Ancient Conserved Domain (ACD) are highly conserved in many different taxonomic species. Particularly, Acdp proteins showed very strong AA homologies to the bacteria CorC protein (35% AA identity with 55% homology), which is involved in magnesium and cobalt efflux. The Acdp genes are widely expressed in all tissues tested except for Acdp1, which is only highly expressed in the brain with low levels of expression in kidney and testis. Immunostaining of Acdp1 in hippocampus neurons revealed a predominant localization on the plasma membrane. Conclusion: The Acdp genes are evolutionarily conserved in diverse species and ubiquitously expressed throughout development and adult tissues suggesting that Acdp may be an essential gene. Acdp showed strong homology to bacteria CorC protein and predominantly localized on the plasma membrane. These results suggest that Acdp is probably a family of proteins involved in ion transport in mammalian cells. [ABSTRACT FROM AUTHOR]

We have recently cloned four novel human genes that encode the ancient conserved domain proteins (ACDP). The full-length cDNA sequence of ACDP1 consists of 5898 bp and encodes a predicted protein of 951 amino acids (AA). The transcript for ACDP2 has 4058 bp of cDNA sequence, encoding a protein of 875 AA. ACDP3 contains 3113 bp of cDNA sequence and encodes a putative protein of 707 AA. ACDP4 contains 4765 bp of cDNA sequence and encodes a protein of 775 AA. The ACDP genes belong to a highly conserved new gene family. The conserved region showed 62.8% of nucleotide sequence identity, and 65.5% of AA identity with 92% of AA homologies among ACDP members. The conserved domain is also found in genes from evolutionarily divergent species from bacteria, yeast, Caenorhabditis elegans, and Drosophila melanogaster to mammals. All ACDP genes except ACDP1 have a ubiquitous expression pattern while ACDP1 expression is restricted to the brain and testis. Immunofluorescence staining of premeablized HeLa cells showed that ACDP proteins are predominantly localized in the nucleus. Sequence homology analyses revealed AA property and structural homologies between the ACD domain and cyclin molecules. [Copyright &y& Elsevier]

The genus Impatiens comprises more than 1000 species and displays enormous morphological diversity. As a taxon that is notoriously difficult to classify morphologically, the taxonomic significance of pollen morphology has been discussed in previous studies. However, there was only limited study on the evolution of palynological and macroscopic character in this genus before. In this paper, we observed pollen of 143 species of Impatiens, including all representatives of infrageneric groups and discussed their taxonomic value. Meanwhile, based on the reconstructed phylogenetic framework, we selected five pollen traits, and nine macroscopic traits including both vegetative and reproductive organs for evolutionary analysis. The character reconstruction showed that the morphology and number of aperture, granules in lumina, seed number of per capsule, number of sepals, lateral united petals connate, spur length, and phyllotaxy could be identified as unambiguous, while other characters were ambiguous in the last common ancestor of Impatiens. The results of comprehensively macroscopic characters and palynological evidence suggest that these traits experienced a complicated evolution, exhibit high levels of instability and variability and occur character multiple reversals in the evolutionary processes of Impatiens due to different selection pressures. In addition, we found that there is an evident mosaic evolution in this genus. Pollen and macroscopic character are conserved with a slower evolutionary rate in the I. subgen. Clavicarpa, however, these characters showed higher diversity with a rapid rate of evolution in the I. subgen. Impatiens. Furthermore, the relationship between floral morphology and pollinators was discussed. [ABSTRACT FROM AUTHOR]

Impatiens rapiformis (Balsaminaceae), a new species from Malipo County, Yunnan, China, is described and illustrated. The new species is superficially similar to I. apalophylla, I. malipoensis and I. guizhouensis, but differs by having cylindric or subfusiform root tuber, elliptic or obovate‐oblong leaf blades and falcate outer lateral sepals. The characters of its seed micromorphology and pollen morphology under SEM are given. A preliminary molecular phylogenetic study suggests that I. rapiformis should be placed in I. subg. Clavicarpa. [ABSTRACT FROM AUTHOR]

Aldehyde dehydrogenase 2 (ALDH2), an acetaldehyde dehydrogenase in mitochondria, is primarily responsible for metabolizing alcohol-derived acetaldehyde and other endogenous aldehydes. Inactivating ALDH2 rs671 polymorphism is found in up to 8 % of the global population and 40 % of the East Asian population. Recent studies have shown that rs671 SNP mutation in the human ALDH2 gene is associated with an increased risk of metabolic dysfunction-associated steatotic liver diseases (MASLD), but the mechanism remains unclear. Here, we identify the role of ALDH2 in MASLD. Firstly, ALDH2 activity was lower in MASLD patients and the methionine-choline deficiency (MCD) diet induced MASLD model. Secondly, activation of ALDH2 activity with Alda-1 (ALDH2 agonist) attenuated MCD-diet induced hepatic triglyceride (TG) accumulation and steatosis, whereas the opposite result was observed with cyanamide (CYA, ALDH2 inhibitor). Furthermore, ALDH2 deficiency exacerbated hepatic steatosis, inflammation, and fibrosis in the MCD-diet induced mice. RNA sequencing (RNA-seq) revealed that oxysterol 7-α hydroxylase (Cyp7b1) and the related metabolic pathway significantly changed in the MCD-diet challenged ALDH2−/− mice. In ALDH2−/− mice, the expression of Cyp7b1 was downregulated and FXR/SHP signaling was inhibited, reducing the alternative bile acid (BA) synthetic pathway. In our in vitro experiments, knockdown of ALDH2 exacerbated TG accumulation in hepatocytes, whereas the opposite result was observed with overexpression of ALDH2. Moreover, chenodeoxycholic acid (CDCA) rescued ALDH2 downregulation induced TG accumulation in hepatocytes. Our study reveals that ALDH2 attenuates hepatocyte steatosis by regulating the alternative BA synthesis pathway, and ALDH2 may serve as a potential target for the treatment of MASLD. [Display omitted] • MASLD induces a decrease in hepatic ALDH2 activity. • ALDH2 deficiency down-regulates BA metabolism pathway-related genes in liver and exacerbates hepatic steatosis, inflammation and fibrosis. • ALDH2 attenuates hepatocyte steatosis by upregulating Cyp7b1 related alternative BA synthesis pathway and FXR/SHP signaling. • CDCA can alleviate ALDH2 downregulation induced TG accumulation in hepatocytes. [ABSTRACT FROM AUTHOR]

Background: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result: Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion: Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on the association between type 1 diabetes and multiple polymorphisms in and near the gene SUMO4, encoding a new small ubiquitin-like modifier.

Abnormal level of glutathione (GSH) was usually related to some physiological and pathological diseases. Thus, developing an intelligent probe for the quantification of GSH was of great significance. Here, we proposed a general, simple, and rapid in situ synthesis strategy for preparing a novel plasmonic core-shell nanoprobe gold nanobipyramids@zeolitic imidazolate framework-67 (Au NBPs@ZIF-67) to realize the quantification of GSH in human serum sample at the single particle level. Mechanism research showed that the Co2+ (the metal node of ZIF-67) would be reduced by GSH, which resulted in the breakdown of ZIF-67 in the presence of GSH, and the scattering color of the nanoprobe would change from green to red under dark-field microscopy. Tricolor (RGB) analysis exhibited that the R/G value was linearly related to the concentration of GSH in the range of 0.01–1 μM (R 2 = 0.999) and the detection limit was 5.7 nM. Besides, this GSH sensing strategy exhibited high selectivity, which demonstrated a satisfactory recovery in human serum sample. This work provided a general method of synthesizing a type of intelligent core-shell scattering nanoprobe and the single particle detection strategy indicated promising application under the biological milieu. • A general synthesis strategy was proposed to perpare Au NBPs@ZIF-67 nanoprobes. • The coordination metal center endows the composite probe with a universal redox response ability. • The glutathione detection strategy possessed high spatial resolution. [ABSTRACT FROM AUTHOR]

Nanoplastics (NPs) are emerging pollutants posing risks to marine biota and human health due to their small size and high bioavailability. However, there are still knowledge gaps regarding effects of co-existing pollutants on NPs toxicity to marine organisms at their respective environmentally relevant concentrations. Herein we investigated developmental toxicity and histopathological alterations caused by co-exposure of polystyrene nanoplastics (PS-NPs) and bisphenol A (BPA) to marine medaka, Oryzias melastigma. Embryos at 6 h post-fertilization were exposed to 50-nm PS-NPs (55 μg/L) or BPA (100 μg/L) or co-exposed to a combination of both. Results showed that PS-NPs exhibited decreased embryonic heart rate, larval body length, and embryonic survival as well as larval deformities such as hemorrhaging and craniofacial abnormality. When co-exposed, BPA mitigated all the adverse developmental effects caused by PS-NPs. PS-NPs also led to an increase in histopathological condition index of liver with early inflammatory responses, while co-exposure of BPA with PS-NPs did not. Our data suggest that the toxicity reduction of PS-NPs in the presence of BPA might result from the decreased bioaccumulation of PS-NPs caused by the interaction between BPA and PS-NPs. This study unveiled the impact of BPA on the toxicity of nanoplastics in marine fish during early developmental stages and highlight the need of more research on the long-term effects of complex mixtures in the marine environment by applying omics approaches to better understand the toxicity mechanism. [Display omitted] • PS-NPs showed a declined waterborne concentration in the presence of BPA. • PS-NPs caused mortality, growth inhibition and deformities of developing medaka. • PS-NPs caused liver inflammatory responses with vacuolation, apoptosis and necrosis. • BPA mitigated the developmental toxicity of PS-NPs. • BPA reduced the liver inflammatory responses caused by PS-NPs. [ABSTRACT FROM AUTHOR]

Background: The HIN-200 family genes in humans have been linked to several autoimmune diseases-particularly to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, its human counterpart gene cluster, the Ifi200 family in mice, has been linked to spontaneous arthritis disease (SAD). However, many immune-mediated diseases (including RA and SLE) show gender difference. Understanding whether or not and how these genes play a role in sex difference in immune-mediated diseases is essential for diagnosis/treatment.Methods: This study takes advantage of the whole genome gene expression profiles of recombinant inbred (RI) strain populations from female and male mice to analyze potential sex differences in a variety of genes in disease pathways. Expression levels and regulatory QTL of Ifi200 family genes between female and male mice were first examined in a large mouse population, including RI strains derived from C57BL/6J, DBA/2J (BXD), and classic inbred strains. Sex similarities and differences were then analyzed for correlations with gene expression levels between genes in the Ifi200 family and four selected gene sets: known immune Ifi200 pathway-related genes, lupus-relevant genes, osteoarthritis- (OA-) and RA-relevant genes, and sex hormone-related genes.Results: The expression level of Ifi202b showed the most sex difference in correlation with known immune-related genes (the P value for Ifi202b is 0.0004). Ifi202b also showed gender difference in correlation with selected sex hormone genes, with a P value of 0.0243. When comparing coexpression levels between Ifi200 genes and lupus-relevant genes, Ifi203 and Ifi205 showed significant sex difference (P values: 0.0303 and 0.002, resp.). Furthermore, several key genes (e.g., Csf1r, Ifnb1, IL-20, IL-22, IL-24, Jhdm1d, Csf1r, Ifnb1, IL-20, IL-22, IL-24, and Tgfb2 that regulate sex differences in immune diseases) were discovered.Conclusions: Different genes in the Ifi200 family play different roles in sex difference among dissimilar pathways of these four gene groups. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained β cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory β cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The article identifies C-C motif chemokine receptor 2 (CCR2) as the host entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV), shedding light on its previously uncharacterized mode of entry. Topics include CCR2's role in enhancing SFTSV binding, its connection to disease pathogenesis, and its potential as a target for anti-SFTSV therapeutics.

Impatiens spiralis, a new species of Balsaminaceae from Hekou County, Yunnan, China, is described and illustrated. This new species is similar to I. hongkongensis, but differs in its obovate‐lanceolate or oblong lamina, without glands at base, spirally curved spur and dorsal petal suborbicular or oblate. Moreover, a phylogenetic analysis based on nuclear ITS and plastid atpB‐rbcL suggests that the new species should be placed in I. subg. Clavicarpa. [ABSTRACT FROM AUTHOR]

The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented CD8+ T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on CD8+ T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage- CD8+ T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis. [ABSTRACT FROM AUTHOR]

Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13-Mec1 interaction revealed two previously unrecognized protein regions, the Mec1-Binding Region (MBR) on Atg13 and the Atg13-Binding Region (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS. [ABSTRACT FROM AUTHOR]

In situ growing transition metals on N‐doped carbon by atomic doping produces a class of promising alternatives to replace Pt‐based catalysts for redox reactions, yet still suffer from unsatisfactory activity and durability in acidic and basic media. Herein, a simple synthetic strategy to fabricate an MnO modifying Co‐Nx/C catalyst with high activity and robust durability is presented. The interphase engineering well controls the Co and N species in the carbon matrix, affording the material with more pyridine N and graphite N; the interaction between Co‐Nx and MnO phase is also well discussed. Accordingly, the obtained Co‐Nx/C‐MnO catalyst exhibits excellent electrocatalytic properties towards oxygen reduction reaction, achieving a half‐wave potential of 0.87 and 0.66 V versus reversible hydrogen electrode in 0.1 m KOH and 0.1 m HClO4 solutions, as well as excellent durability with only −16.9 and −12.2 mV shift after 1000 cycles, respectively. This study provides insights into the design of noble‐metal‐free electrocatalysts from the perspective of active sites and catalyst carriers. [ABSTRACT FROM AUTHOR]

The dispersion and filler network of fibrillar silicate (FS) in elastomers were studied. The results showed that a good dispersion of FS in matrix during mechanical blending in unvulcanized composites contributed to a strong FS filler network, different from that of traditional reinforcing fillers. Meanwhile, the filler re-aggregation during vulcanization caused by the overlapping and intertwining of FS further strengthened the filler network. The factors including Mooney viscosity and molecular polarity of elastomer, type and amount of silane coupling agents used for filler modification, that may influence the filler network, were studied. Our study helps us to understand the mechanism for the formation of filler network of FS in elastomers and provides guidance for the preparation of high performance FS/elastomer composites. [ABSTRACT FROM AUTHOR]

Macrophages are widely distributed in various tissues and organs. They not only participate in the regulation of innate and adaptive immune response, but also play an important role in tissue homeostasis. Dysregulation of macrophage function is closely related to the initiation, development and prognosis of multiple diseases, including infection and tumorigenesis. Forkhead box transcription factor O1 (FoxO1) is an important member among the forkhead box transcription factor family. Through directly binding to the promoter regions of downstream target genes, FoxO1 is implicated in cell proliferation, apoptosis, metabolic activities and other biological processes. In this review, we summarized the regulatory role of FoxO1 in macrophage phagocytosis, migration, differentiation and inflammatory activation. We also emphasized that macrophage reciprocally modulated FoxO1 activity via a post-translational modification (PTM) dominant manner. [ABSTRACT FROM AUTHOR]

Background and Purpose: Tacrolimus a first‐line medication used after transplantation can induce β‐cell dysfunction, causing new‐onset diabetes mellitus (NODM). Regenerating islet‐derived protein 3 gamma (Reg3g), a member of the pancreatic regenerative gene family, has been reported to improve type 1 diabetes by promoting β‐cell regeneration. We aim to investigate the role of Reg3g in reversing tacrolimus‐induced β‐cell dysfunction and NODM in mice. Experimental Approach Circulating REG3A (the human homologue of mouse Reg3g) in heart transplantation patients treated with tacrolimus was detected. The glucose‐stimulated insulin secretion and mitochondrial functions, including mitochondria membrane potential (MMP), mitochondria calcium, ATP production, oxygen consumption rate and mitochondrial morphology were investigated in β‐cells. Additionally, effects of Reg3g on tacrolimus‐induced NODM in mice were analysed. Key Results: Circulating REG3A level in heart transplantation patients with NODM significantly decreased compared with those without diabetes. Tacrolimus down‐regulated Reg3g via inhibiting STAT3‐mediated transcription activation. Moreover, Reg3g restored glucose‐stimulated insulin secretion suppressed by tacrolimus in β‐cells by improving mitochondrial functions, including increased MMP, mitochondria calcium uptake, ATP production, oxygen consumption rate and contributing to an intact mitochondrial morphology. Mechanistically, Reg3g increased accumulation of pSTAT3(Ser727) in mitochondria by activating ERK1/2‐STAT3 signalling pathway, leading to restoration of tacrolimus‐induced mitochondrial impairment. Reg3g overexpression also effectively mitigated tacrolimus‐induced NODM in mice. Conclusion and Implications: Reg3g can significantly ameliorate tacrolimus‐induced β‐cell dysfunction by restoring mitochondrial function in a pSTAT3(Ser727)‐dependent manner. Our observations identify a novel Reg3g‐mediated mechanism that is involved in tacrolimus‐induced NODM and establish the novel role of Reg3g in reversing tacrolimus‐induced β‐cell dysfunction. [ABSTRACT FROM AUTHOR]

A catalyst-free co-reaction luminol-H2O2–K2S2O8 chemiluminescence (CL) system was developed, with long-life and high-intensity emission, and CL emission lasting for 6 h. A possible mechanism of persistent and intense emission in this CL system was discussed in the context of CL spectra, cyclic voltammetry, electron spin resonance (ESR), and the effects of radical scavengers on luminol-H2O2–K2S2O8 system. H2O2 and K2S2O8 co-reactants can promote each other to continuously generate corresponding radicals (OH•, 1O2, O2•−, SO4•−) that trigger the CL emission of luminol. H2O2 can also be constantly produced by the reaction of K2S2O8 and H2O to further extend the persistence of this CL system. CL emission can be quenched via ascorbic acid (AA), which can be generated through hydrolysis reaction of L-ascorbic acid 2-phosphate trisodium salt (AAP) and alkaline phosphatase (ALP). Next, a CL-based method was established for the detection of ALP with good linearity from 0.08 to 5 U·L−1 and a limit of detection of 0.049 U·L−1. The proposed method was used to detect ALP in human serum samples. [ABSTRACT FROM AUTHOR]

Aging has been recognized to be a highly complex biological health problem with a high risk of chronic diseases, including type 2 diabetes, atherosclerosis, chronic bronchitis or emphysema, cancer and Alzheimer's disease. Particularly, age-related turnover in adipose tissue is a major contributor to metabolic syndromes and shortened lifespan. Adipocytes undergo senescence in early stage, which results in adipose tissue metabolic dysfunction, redistribution, and inflammation. The well-established association between DNA methylation (DNAm) and aging has been observed in the past few decades. Indeed, age-related alteration in DNAm is highly tissue-specific. This review intends to summarize the advancements how DNAm changes coupled with aging process in adipose tissue, by which DNAm regulates cellular senescence, metabolic function, adipokine secretion and beiging process in adipocytes. Elucidation of the effect of DNAm on adipose aging would have great potential to the development of epigenetic therapeutic strategies against aging-related diseases in clinical settings. [ABSTRACT FROM AUTHOR]

Recent studies have shown mitochondrial fragmentation during cell stress and have suggested a role for the morphological change in mitochondrial injury and ensuing apoptosis. However, the underlying mechanism remains elusive. Here we demonstrate that mitochondrial fragmentation facilitates Bax insertion and activation in mitochondria, resulting in the release of apoptogenic factors. In HeLa cells, overexpression of mitofusins attenuated mitochondrial fragmentation during cisplatin- and azide-induced cell injury, which was accompanied by less apoptosis and less cytochrome c release from mitochondria. Similar effects were shown by inhibiting the mitochondrial fission protein Drp1 with a dominant negative mutant (dn-Drp1). Mitofusins and dn-Drp1 did not seem to significantly affect Bax translocation/accumulation to mitochondria; however, they blocked Bax insertion and activation in mitochondrial membrane. Consistently, in rat kidney proximal tubular cells, small interfering RNA knockdown of Drp1 prevented mitochondrial fragmentation during azide-induced ATP depletion, which was accompanied by less Bax activation, insertion, and oligomerization in mitochondria. These cells released less cytochrome c and AIF from mitochondria and showed significantly lower apoptosis. Finally, mitofusin-null mouse embryonic fibroblasts (MEF) had fragmented mitochondria. These MEFs were more sensitive to cisplatin-induced Bax activation, release of cytochrome c, and apoptosis. Together, this study provides further support for a role of mitochondrial fragmentation in mitochondrial injury and apoptosis. Mechanistically, mitochondrial fragmentation may sensitize the cells to Bax insertion and activation in mitochondria, facilitating the release of apoptogenic factors and consequent apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Foot-and-mouth disease virus is a positive-sense, single-stranded RNA virus with a negative strand as its replication intermediate, which can cause severe acute infection in sensitive cell lines. To investigate better the actual state of virus infection, there is a need to measure the amount of FMDV RNA in a single acutely infected cell rather than in a large number of cells. Therefore, in the present study, a strand-specific single-cell quantitative real-time RT-PCR was developed to analyze the RNA or FMDV. This new method uses two techniques in concert with each other: a technique for isolating single cells with micromanipulators, which is coupled to an assay for detecting viral RNA by real-time RT-PCR. In the assay of acute infection, 185 of 224 (82.6%) single-cell samples were positive and contained viral genome copies ranging from several to thousands, and up to 1000000 copies. However, not all cells were infected and there were differences in the number of viral RNA copies between cells. A single-cell quantitative RT-PCR was validated to be feasible and effective. [Copyright &y& Elsevier]

Cisplatin induces renal cell injury and death, resulting in nephrotoxicity that limits its use in cancer therapy. Using cell culture models, recent work has suggested the involvement of p53 in renal cell apoptosis during cisplatin treatment. However, the signals upstream of p53 remain elusive. ATM and ATR are critical regulators of p53 under various conditions of DNA damage. Here, we show that ATM, and not ATR, was proteolytically cleaved into specific fragments of ~210 and 150 kDa during cisplatin-induced tubular cell apoptosis. ATM cleavage was paralleled by the development of apoptosis. VAD, a broad-spectrum inhibitor of caspases, attenuated the cleavage of ATM, whereas the inhibitors of specific caspases were less effective. In caspase-3-deficient MCF-7 cells, ATM was cleaved, releasing the 210- but not the 150-kDa fragment. Recombinant caspase-3 was much more effective than caspase-7 in cleaving ATM that was immunoprecipitated from cell lysates. During cisplatin incubation, VAD protected ATM and enhanced p53 phosphorylation. In vitro assay of protein kinase activity further showed that ATM immunoprecipitated from cisplatin-treated cells had significantly lower kinase activity toward p53 than that from control cells. Importantly, the protein kinase activity was restored in ATM that was protected by VAD during cisplatin incubation. ATM deficiency sensitized the cells to cisplatin-induced apoptosis, suggesting a cytoprotective role of ATM in this experimental model. Thus proteolysis of ATM by caspases may inactivate this regulatory molecule to facilitate the progression of apoptosis. [ABSTRACT FROM AUTHOR]

Random amplified polymorphism DNA (RAPD) analysis was applied to germplasm characterization in 33 different selected Laminaria male and female gametophytes. The positional homology of the RAPD analysis using sequence characterized applied region (SCAR) method was successfully conducted. A total of 233 polymorphic loci were obtained from 18 selected primers after screening, of which 27 stable and clear bands were selected to construct a fingerprint map for discrimination of each gametophyte. Seven RAPD markers from five primers were finally determined by a computer program to construct the fingerprint map. Three specific markers closely related with gametophytes were obtained and were converted to gametophytic SCAR markers, the first SCAR marker report on Laminaria germplasm and applicable to cultivars identification. These results demonstrated the feasibility of applying RAPD markers to germplasm characterization in selected Laminaria gametophytes, and can provide a molecular basis for breeding new Laminaria strains. [Copyright &y& Elsevier]

Robust neuroprotective effects have been shown for minocycline. Whether it also protects nonneuronal cells or tissues is unknown. More importantly, the mechanisms of minocylcine protection appear multifaceted and remain to be clarified. Here we show that minocycline can protect kidney epithelial cells in vitro and protect the kidneys from ischemic injury in vivo. We further show that Bcl-2 is a key molecular determinant of minocycline protection. Minocycline protected kidney epithelial cells against apoptosis induced by hypoxia, azide, cisplatin, and staurosporine. The protection occurred at mitochondria, involving the suppression of Bax accumulation, outer membrane damage, and cytochrome c release. Minocycline induced Bcl-2, which accumulated in mitochondria and interacted with death-promoting molecules including Bax, Bak, and Bid. Down-regulation of Bcl-2 by specific antisense oligonucleotides abolished the cytoprotective effects of minocycline. Thus, minocycline can protect neuronal as well as nonneuronal cells and tissues. One mechanism for minocycline protection involves the induction of Bcl-2, an antiapoptotic protein. [ABSTRACT FROM AUTHOR]