Mpox (Monkeypox) Virus and Its Co-Infection with HIV, Sexually Transmitted Infections, or Bacterial Superinfections: Double Whammy or a New Prime Culprit?

Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections.

Bacterial community structure analysis of sludge from Taozi lake and isolation of an efficient 17ß-Estradiol (E2) degrading strain Sphingobacterium sp. GEMB-CSS-01.

Environmental challenges arising from organic pollutants pose a significant problem for modern societies. Efficient microbial resources for the degradation of these pollutants are highly valuable. In this study, the bacterial community structure of sludge samples from Taozi Lake (polluted by urban sewage) was studied using 16S rRNA sequencing. The bacterial phyla Proteobacteria, Bacteroidetes, and Chloroflexi, which are potentially important in organic matter degradation by previous studies, were identified as the predominant phyla in our samples, with relative abundances of 48.5%, 8.3%, and 6.6%, respectively. Additionally, the FAPROTAX and co-occurrence network analysis suggested that the core microbial populations in the samples may be closely associated with organic matter metabolism. Subsequently, sludge samples from Taozi Lake were subjected to enrichment cultivation to isolate organic pollutant-degrading microorganisms. The strain Sphingobacterium sp. GEMB-CSS-01, tolerant to sulfanilamide, was successfully isolated. Subsequent investigations demonstrated that Sphingobacterium sp. GEMB-CSS-01 efficiently degraded the endocrine-disrupting compound 17ß-Estradiol (E2). It achieved degradation efficiencies of 80.0% and 53.5% for E2 concentrations of 10 mg/L and 20 mg/L, respectively, within 10 days. Notably, despite a reduction in degradation efficiency, Sphingobacterium sp. GEMB-CSS-01 retained its ability to degrade E2 even in the presence of sulfanilamide concentrations ranging from 50 to 200 mg/L. The findings of this research identify potential microbial resources for environmental bioremediation, and concurrently provide valuable information about the microbial community structure and patterns within Taozi Lake.

Uterine rupture in patients with a history of hysteroscopy procedures: Case series and review of literature.

RATIONALE: Uterine rupture during pregnancy poses significant risks to both the fetus and the mother, resulting in high mortality and morbidity rates. While awareness of uterine rupture prevention after a cesarean section has increased, insufficient attention has been given to cases caused by pregnancy following hysteroscopy surgery. PATIENT CONCERNS: We report 2 cases here, both of whom had a history of hysteroscopy surgery and presented with severe abdominal pain during pregnancy. DIAGNOSES: Both patients had small uterine ruptures, with no significant abnormalities detected on ultrasonography. The diagnosis was confirmed by a CT scan, which showed hemoperitoneum. INTERVENTIONS: We performed emergency surgeries for the 2 cases. OUTCOMES: We repaired the uterus in 2 patients during the operation. Both patients recovered well. The children survived. No abnormalities were detected during their follow-up visits. LESSONS: Attention should be paid to the cases of pregnancy after hysteroscopy.

Copper removal from aqueous solutions by white rot fungus Pleurotus ostreatus GEMB-PO1 and its potential in co-remediation of copper and organic pollutants.

Addressing the environmental contamination from heavy metals and organic pollutants remains a critical challenge. This study explored the resilience and removal potential of Pleurotus ostreatus GEMB-PO1 for copper. P. ostreatus GEMB-PO1 showed significant tolerance, withstanding copper concentrations up to 2 mM. Its copper removal efficiency ranged from 64.56 % at 0.5 mM to 22.90 % at 8 mM. Transcriptomic insights into its response to copper revealed a marked upregulation in xenobiotic degradation-related enzymes, such as laccase and type II peroxidases. Building on these findings, a co-remediation system using P. ostreatus GEMB-PO1 was developed to remove both copper and organic pollutants. While this approach significantly enhanced the degradation efficiency of organic contaminants, it concurrently exhibited a diminished efficacy in copper removal within the composite system. This study underscores the potential of P. ostreatus GEMB-PO1 in environmental remediation. Nevertheless, further investigation is required to optimize the simultaneous removal of organic pollutants and copper.

Identifying the distinct roles of dual dopants in stabilizing the platinum-nickel nanowire catalyst for durable fuel cell.

Stabilizing active PtNi alloy catalyst toward oxygen reduction reaction is essential for fuel cell. Doping of specific metals is an empirical strategy, however, the atomistic insight into how dopant boosts the stability of PtNi catalyst still remains elusive. Here, with typical examples of Mo and Au dopants, we identify the distinct roles of Mo and Au in stabilizing PtNi nanowires catalysts. Specifically, due to the stronger interaction between atomic orbital for Ni-Mo and Pt-Au, the Mo dopant mainly suppresses the outward diffusion of Ni atoms while the Au dopant contributes to the stabilization of surface Pt overlayer. Inspired by this atomistic understanding, we rationally construct the PtNiMoAu nanowires by integrating the different functions of Mo and Au into one entity. Such catalyst assembled in fuel cell cathode thus presents both remarkable activity and durability, even surpassing the United States Department of Energy technical targets for 2025.

La-related protein 4 is enriched in vaccinia virus factories and is required for efficient viral replication in primary human fibroblasts.

In addition to the 3'-poly(A) tail, vaccinia virus mRNAs synthesized after viral DNA replication (post-replicative mRNAs) possess a 5'-poly(A) leader that confers a translational advantage in virally infected cells. These mRNAs are synthesized in viral factories, the cytoplasmic compartment where vaccinia virus DNA replication, mRNA synthesis, and translation occur. However, a previous study indicates that the poly(A)-binding protein (PABPC1)-which has a well-established role in RNA stability and translation-is absent in the viral factories. This prompts the question of whether other poly(A)-binding proteins engage vaccinia virus post-replicative mRNA in viral factories. Here, in this study, we found that La-related protein 4 (LARP4), a poly(A) binding protein, was enriched in viral factories in multiple types of cells during vaccinia virus infection. Further studies showed that LARP4 enrichment in the viral factories required viral post-replicative gene expression and functional decapping enzymes encoded by vaccinia virus. We further showed that knockdown of LARP4 expression in human foreskin fibroblasts (HFFs) reduced vaccinia virus DNA replication, post-replicative protein levels, and viral production. Interestingly, the knockdown of LARP4 expression also reduced protein levels from transfected mRNA containing a 5'-poly(A) leader in vaccinia virus-infected and uninfected HFFs. Taken together, our results identified a poly(A)-binding protein, LARP4, being enriched in the vaccinia virus viral factories and facilitating viral replication in HFFs. IMPORTANCE Vaccinia virus, the prototype poxvirus, encodes over 200 open reading frames (ORFs). Over 90 of vaccinia virus ORFs are transcribed post-viral DNA replication. All these mRNAs contain a 5'-poly(A) leader, as well as a 3'-poly(A) tail. They are synthesized in viral factories, where vaccinia virus DNA replication, mRNA synthesis, and translation occur. However, surprisingly, the poly(A) binding protein, PABPC1, that is important for mRNA metabolism and translation is not present in the viral factories, suggesting other poly(A) binding protein(s) may be present in viral factories. Here, we found another poly(A)-binding protein, La-related protein 4 (LARP4), enriched in viral factories during vaccinia virus infection. We also showed that LARP4 enrichment in the viral factories depends on viral post-replicative gene expression and functional viral decapping enzymes. The knockdown of LARP4 expression in human foreskin fibroblasts reduced vaccinia virus DNA replication, post-replicative gene expression, and viral production.

Antiviral activities of two nucleos(t)ide analogs against vaccinia, mpox, and cowpox viruses in primary human fibroblasts.

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox (formerly monkeypox). Identifying novel and potent antiviral compounds is critical to successful drug development targeting poxviruses. Here we tested two compounds, nucleoside trifluridine, and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV), mpox virus (MPXV), and cowpox virus (CPXV) in physiologically relevant primary human fibroblasts. Both compounds potently inhibited the replication of VACV, CPXV, and MPXV (MA001 2022 isolate) in plaque assays. In our recently developed assay based on a recombinant VACV expressing secreted Gaussia luciferase, they both exhibited high potency in inhibiting VACV replication with EC50s in the low nanomolar range. In addition, both trifluridine and adefovir dipivoxil inhibited VACV DNA replication and downstream viral gene expression. Our results characterized trifluridine and adefovir dipivoxil as strong poxvirus antiviral compounds and further validate the VACV Gaussia luciferase assay as a highly efficient and reliable reporter tool for identifying poxvirus inhibitors. Given that both compounds are FDA-approved drugs, and trifluridine is already used to treat ocular vaccinia, further development of trifluridine and adefovir dipivoxil holds great promise in treating poxvirus infections, including mpox.

QTL Mapping for Ovary- and Fruit-Related Traits in Cucumis sativus-C. hystrix Introgression Line IL52.

IL52 is a valuable introgression line obtained from interspecific hybridization between cultivated cucumber (Cucumis sativus L., 2n = 14) and the wild relative species C. hystrix Chakr. (2n = 24). IL52 exhibits high resistance to a number of diseases, including downy mildew, powdery mildew, and angular leaf spot. However, the ovary- and fruit-related traits of IL52 have not been thoroughly investigated. Here, we conducted quantitative trait loci (QTL) mapping for 11 traits related to ovary size, fruit size, and flowering time using a previously developed 155 F7:8 RIL population derived from a cross between CCMC and IL52. In total, 27 QTL associated with the 11 traits were detected, distributed on seven chromosomes. These QTL explained 3.61% to 43.98% of the phenotypic variance. Notably, we identified a major-effect QTL (qOHN4.1) on chromosome 4 associated with the ovary hypanthium neck width and further delimited it into a 114-kb candidate region harboring 13 candidate genes. Furthermore, the QTL qOHN4.1 is co-localized with the QTL detected for ovary length, mature fruit length, and fruit neck length, all residing within the consensus QTL FS4.1, suggesting a plausible pleiotropic effect.

La-related protein 4 is enriched in vaccinia virus factories and is required for efficient viral replication in primary human fibroblasts.

In addition to the 3'-poly(A) tail, vaccinia virus mRNAs synthesized after viral DNA replication (post-replicative mRNAs) possess a 5'-poly(A) leader that confers a translational advantage in virally infected cells. These mRNAs are synthesized in viral factories, the cytoplasmic compartment where vaccinia virus DNA replication, mRNA synthesis, and translation occur. However, a previous study indicates that the poly(A)-binding protein (PABPC1)-which has a well-established role in RNA stability and translation-is not present in the viral factories. This prompts the question of whether another poly(A)-binding protein engages vaccinia virus post-replicative mRNA in viral factories. In this study, we found that La-related protein 4 (LARP4), a poly(A) binding protein, was enriched in viral factories in multiple types of cells during vaccinia virus infection. Further studies showed that LARP4 enrichment in the viral factories required viral post-replicative gene expression and functional decapping enzymes encoded by vaccinia virus. We further showed that knockdown of LARP4 expression in human foreskin fibroblasts (HFFs) significantly reduced vaccinia virus post-replicative gene expression and viral replication. Interestingly, the knockdown of LARP4 expression also reduced 5'-poly(A) leader-mediated mRNA translation in vaccinia virus-infected and uninfected HFFs. Together, our results identified a poly(A)-binding protein, LARP4, enriched in the vaccinia virus viral factories and facilitates viral replication and mRNA translation. Importance: Poxviruses are a family of large DNA viruses comprising members infecting a broad range of hosts, including many animals and humans. Poxvirus infections can cause deadly diseases in humans and animals. Vaccinia virus, the prototype poxvirus, encodes over 200 open reading frames (ORFs). Over 90 of vaccinia virus ORFs are transcribed post-viral DNA replication. All these mRNAs contain a 5'-poly(A) leader, as well as a 3'-poly(A) tail. They are synthesized in viral factories, where vaccinia virus DNA replication, mRNA synthesis and translation occur. However, surprisingly, the poly(A) binding protein (PABPC1) that is important for mRNA metabolism and translation is not present in the viral factories, suggesting other poly(A) binding protein(s) may be present in viral factories. Here we found another poly(A)-binding protein, La-related protein 4 (LARP4), is enriched in viral factories during vaccinia virus infection. We also showed that LARP4 enrichment in the viral factories depends on viral post-replicative gene expression and functional viral decapping enzymes. The knockdown of LARP4 expression in human foreskin fibroblasts (HFFs) significantly reduced vaccinia virus post-replicative gene expression and viral replication. Overall, this study identified a poly(A)-binding protein that plays an important role in vaccinia virus replication.

Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts.

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts. Both trifluridine and adefovir dipivoxil potently inhibited replication of VACV and MPXV (MA001 2022 isolate) in a plaque assay. Upon further characterization, they both conferred high potency in inhibiting VACV replication with half maximal effective concentrations (EC 50 ) at low nanomolar levels in our recently developed assay based on a recombinant VACV secreted Gaussia luciferase. Our results further validated that the recombinant VACV with Gaussia luciferase secretion is a highly reliable, rapid, non-disruptive, and simple reporter tool for identification and chracterization of poxvirus inhibitors. Both compounds inhibited VACV DNA replication and downstream viral gene expression. Given that both compounds are FDA-approved drugs, and trifluridine is used to treat ocular vaccinia in medical practice due to its antiviral activity, our results suggest that it holds great promise to further test trifluridine and adefovir dipivoxil for countering poxvirus infection, including mpox.

A universal synthesis of ultrathin Pd-based nanorings for efficient ethanol electrooxidation.

Metallic nanorings (NRs) with open hollow structures are of particular interest in energy-related catalysis due to their unique features, which include the high utilization of active sites and facile accessibility for reactants. However, there is still a lack of general methods for synthesizing Pd-based multimetallic NRs with a high catalytic performance. Herein, we develop a template-directed strategy for the synthesis of ultrathin PdM (M = Bi, Sb, Pb, BiPb) NRs with a tunable size. Specifically, ultrathin Pd nanosheets (NSs) are used as a template to steer the deposition of M atoms and the interatomic diffusion between Pd and M, subsequently resulting in the hollow structured NRs. Taking the ethanol oxidation reaction (EOR) as a proof-of-concept application, the PdBi NRs deliver a substantially improved activity relative to the Pd NSs and commercial Pd/C catalysts, simultaneously showing outstanding stability and CO tolerance. Mechanistically, density functional theory (DFT) calculations disclose that the incorporation of Bi reduces the energy barrier of the rate-determining step in the EOR C2-path, which, together with the high ratio of exposed active sites, endows the PdBi NRs with an excellent EOR activity. We believe that our work can illuminate the general synthesis of multimetallic NRs and the rational design of advanced electrocatalysts.

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles.

We utilized a high-throughput cell-based assay to screen several chemical libraries for inhibitors of herpes simplex virus 1 (HSV-1) gene expression. From this screen, four aurora kinase inhibitors were identified that potently reduced gene expression during HSV-1 lytic infection. HSV-1 is known to interact with cellular kinases to regulate gene expression by modulating the phosphorylation and/or activities of viral and cellular proteins. To date, the role of aurora kinases in HSV-1 lytic infection has not been reported. We demonstrated that three aurora kinase inhibitors strongly reduced the transcript levels of immediate-early (IE) genes ICP0, ICP4, and ICP27 and impaired HSV-1 protein expression from all classes of HSV-1, including ICP0, ICP4, ICP8, and gC. These restrictions caused by the aurora kinase inhibitors led to potent reductions in HSV-1 viral replication. The compounds TAK 901, JNJ 7706621, and PF 03814735 decreased HSV-1 titers by 4,500-, 13,200-, and 8,400-fold, respectively, when present in a low micromolar range. The antiviral activity of these compounds correlated with an apparent decrease in histone H3 phosphorylation at serine 10 (H3S10ph) during viral infection, suggesting that the phosphorylation status of H3 influences HSV-1 gene expression. Furthermore, we demonstrated that the aurora kinase inhibitors also impaired the replication of other RNA and DNA viruses. These inhibitors significantly reduced yields of vaccinia virus (a poxvirus, double-stranded DNA, cytoplasmic replication) and mouse hepatitis virus (a coronavirus, positive-sense single-strand RNA [ssRNA]), whereas vesicular stomatitis virus (rhabdovirus, negative-sense ssRNA) yields were unaffected. These results indicated that the activities of aurora kinases play pivotal roles in the life cycles of diverse viruses. IMPORTANCE We have demonstrated that aurora kinases play a role during HSV-1 lytic infection. Three aurora kinase inhibitors significantly impaired HSV-1 immediate-early gene expression. This led to a potent reduction in HSV-1 protein expression and viral replication. Together, our results illustrate a novel role for aurora kinases in the HSV-1 lytic cycle and demonstrate that aurora kinase inhibitors can restrict HSV-1 replication. Furthermore, these aurora kinase inhibitors also reduced the replication of murine coronavirus and vaccinia virus, suggesting that multiple viral families utilize the aurora kinases for their own replication.

CO2 electroreduction to multicarbon products in strongly acidic electrolyte via synergistically modulating the local microenvironment.

Electrochemical CO2 reduction to multicarbon products faces challenges of unsatisfactory selectivity, productivity, and long-term stability. Herein, we demonstrate CO2 electroreduction in strongly acidic electrolyte (pH ≤ 1) on electrochemically reduced porous Cu nanosheets by combining the confinement effect and cation effect to synergistically modulate the local microenvironment. A Faradaic efficiency of 83.7 ± 1.4% and partial current density of 0.56 ± 0.02 A cm-2, single-pass carbon efficiency of 54.4%, and stable electrolysis of 30 h in a flow cell are demonstrated for multicarbon products in a strongly acidic aqueous electrolyte consisting of sulfuric acid and KCl with pH ≤ 1. Mechanistically, the accumulated species (e.g., K+ and OH-) on the Helmholtz plane account for the selectivity and activity toward multicarbon products by kinetically reducing the proton coverage and thermodynamically favoring the CO2 conversion. We find that the K+ cations facilitate C-C coupling through local interaction between K+ and the key intermediate *OCCO.

Molecular characterization and expression analysis of selenoprotein W gene in rainbow trout (Oncorhynchus mykiss) with dietary selenium levels.

Selenium (Se) plays an essential role in the growth of fish and performs its physiological functions mainly through incorporation into selenoproteins. Our previous studies suggested that the selenoprotein W gene (selenow) is sensitive to changes in dietary Se in rainbow trout. However, the molecular characterization and tissue expression pattern of selenow are still unknown. Here, we revealed the molecular characterization, the tissue expression pattern of rainbow trout selenow and analyzed its response to dietary Se. The open reading frame (ORF) of the selenow gene was composed of 393 base pairs (bp) and encodes a 130-amino-acid protein. The 3' untranslated region (UTR) was 372 bp with a selenocysteine insertion sequence (SECIS) element. Remarkably, the rainbow trout selenow gene sequence was longer than those reported for mammals and most other fish. A ß1-α1-ß2-ß3-ß4-α2 pattern made up the secondary structure of SELENOW. Furthermore, multiple sequence alignment revealed that rainbow trout SELENOW showed a high level of identity with SELENOW from Salmo salar. In addition, the selenow gene was ubiquitously distributed in 13 tissues with various abundances and was predominantly expressed in muscle and brain. Interestingly, dietary Se significantly increased selenow mRNA expression in muscle. Our results highlight the vital role of selenow in rainbow trout muscle response to dietary Se levels and provide a theoretical basis for studies of selenow.

Optimal therapeutic conditions for the neural stem cell-based management of ischemic stroke: a systematic review and network meta-analysis based on animal studies.

BACKGROUND: In order to promote the clinical translation of preclinical findings, it is imperative to identify the most optimal therapeutic conditions and adopt them for further animal and human studies. This study aimed to fully explore the optimal conditions for neural stem cell (NSC)-based ischemic stroke treatment based on animal studies. METHODS: The PubMed, Ovid-Embase, and Web of Science databases were searched in December 2021. The screening of search results, extraction of relevant data, and evaluation of study quality were performed independently by two reviewers. RESULTS: In total, 52 studies were included for data analysis. Traditional meta-analysis showed that NSCs significantly reduced the modified neurological severity score (mNSS) and volume of cerebral infarct in animal models of ischemic stroke. Network meta-analysis showed that allogeneic embryonic tissue was the best source of NSCs. Further, intracerebral transplantation was the most optimal route of NSC transplantation, and the acute phase was the most suitable stage for intervention. The optimal number of NSCs for transplantation was 1-5×105 in mouse models and 1×106 or 1.8×106 in rat models. CONCLUSIONS: We systematically explored the therapeutic strategy of NSCs in ischemic stroke, but additional research is required to develop optimal therapeutic strategies based on NSCs. Moreover, it is necessary to further improve and standardize the design, implementation, measuring standards, and reporting of animal-based studies to promote the development of better animal experiments and clinical research.

Monkeypox emergency: Urgent questions and perspectives.

Amidst the COVID-19 pandemic, we now face another public health emergency in the form of monkeypox virus. As of August 1, the Centers for Disease Control and Prevention report over 23,000 cases in 80 countries. An inclusive and global collaborative effort to understand the biology, evolution, and spread of the virus as well as commitment to vaccine equity will be critical toward containing this outbreak. We share the voices of leading experts in this space on what they see as the most pressing questions and directions for the community.

Early Enteral Nutrition Tolerance in a Duodenal Fistula Patient Undergoing Open Abdomen with Vacuum-assisted Temporary Abdominal Closure.

This case sought to manage a duodenal fistula patient who underwent an open abdomen with vacuum-assisted temporary abdominal closure (VAC) by evaluating his tolerance to early enteral nutrition therapy (ENT). A review of the patient suggested that he developed an abdominal infection as a result of a high duodenal fistula, which necessitated an open abdomen and VAC. Prior to the initiation of ENT, the patient had a patient-generated subjective global assessment (PG-SGA) score of 8 (1st day) suggesting the need for nutritional intervention. Upon ENT intervention, the patient's PG-SGA score dropped to 2 (30th day) indicating an improvement in the nutritional status, probably due to measures such as formulation, implementation, and management of early ENT. The improved nutritional status of the patient led to the success of duodenal fistula repair and abdominal wall defect reconstruction within a short time, thus ensuring a successful surgery. Key Words: Duodenal fistula, Open abdomen, Enteral nutrition.

Glycitein exerts neuroprotective effects in Rotenone-triggered oxidative stress and apoptotic cell death in the cellular model of Parkinson's disease.

Parkinson's disease (PD) is one of the prevalent neurodegenerative diseases among aging populations. Despite recent advancements, still, no therapy exists for the prevention of PD. Given the remarkable pharmacological properties of flavonoids, this study was designed to investigate the protective effects of a plant-derived flavonoid, glycitein in a cellular model of PD. Rotenone, a prevalently used pesticide, has been employed to study the pathology of PD. The results of the present study showed that Glycitein significantly (P<0.05) prevented the rotenone-induced inhibition of cell viability as evident from the MTT assay. Additionally, it was found that the increased ROS levels triggered by rotenone in human SK-N-SH neuroblastoma cells were significantly (P<0.05) diminished upon glycitein treatment. Glycitein treatment also restored the mitochondrial membrane potential of the rotenone treated SK-N-SH cells. These effects of Glycitein were mainly due to its ability to trigger the increased activity of the ROS scavenging enzymes such as GSH, SOD and CAT. The ATP estimates showed that the ATP levels were significantly (P<0.05) reduced in the rotenone treated SK-N-SH cells. Nonetheless, glycitein treatment could restore the ATP levels of the SK-N-SH cells in a dose-dependent manner. Rotenone has also been shown to induce apoptosis in human cells and the results of the annexin V/PI staining showed that glycitein exhibits remarkable potential to prevent in the rotenone triggered apoptosis in SK-N-SH cells. This was also accompanied by alteration in the expression of Bax, Bcl-2 and caspase-3 expression. Taken together, the study indicates that glycitein exhibits neuroprotective effects by preventing rotenone induce oxidative stress and apoptotic cell death. These findings point towards the use of glycitein in the management of neurodegenerative diseases such as PD.

A Poxvirus Decapping Enzyme Colocalizes with Mitochondria To Regulate RNA Metabolism and Translation and Promote Viral Replication.

Decapping enzymes remove the 5' cap of eukaryotic mRNA, leading to accelerated RNA decay. They are critical in regulating RNA homeostasis and play essential roles in many cellular and life processes. They are encoded in many organisms and viruses, including vaccinia virus, which was used as the vaccine to eradicate smallpox. Vaccinia virus encodes two decapping enzymes, D9 and D10, that are necessary for efficient viral replication and pathogenesis. However, the underlying molecular mechanisms regulating vaccinia decapping enzymes' functions are still largely elusive. Here, we demonstrated that vaccinia D10 almost exclusively colocalized with mitochondria. As mitochondria are highly mobile cellular organelles, colocalization of D10 with mitochondria can concentrate D10 locally and mobilize it to efficiently decap mRNAs. Mitochondria were barely observed in "viral factories," where viral transcripts are produced, suggesting that mitochondrial colocalization provides a spatial mechanism to preferentially decap cellular mRNAs over viral mRNAs. We identified three amino acids at the N terminus of D10 that are required for D10's mitochondrial colocalization. Loss of mitochondrial colocalization significantly impaired viral replication, reduced D10's ability to remove the RNA 5' cap during infection, and diminished D10's gene expression shutoff and mRNA translation promotion abilities. IMPORTANCE Decapping enzymes comprise many members from various organisms, ranging from plants, animals, and viruses. The mechanisms regulating their functions vary and are still largely unknown. Our study provides evidence that a vaccinia virus-encoded decapping enzyme, D10, colocalizes with mitochondria. Loss of mitochondrial colocalization significantly impairs viral replication, D10's gene expression shutoff, and mRNA translation promotion ability. Overall, our results suggest that mitochondrial colocalization is a spatial mechanism to concentrate D10 locally and mobilize it to efficiently and preferentially target cellular mRNAs for decapping and promote viral mRNA translation. Our results have broad impacts for understanding the functions and regulatory mechanisms of decapping enzymes.