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1.
Microbiome ; 9(1): 207, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34654476

RESUMO

BACKGROUND: Dimethyl sulfide (DMS) is the dominant volatile organic sulfur in global oceans. The predominant source of oceanic DMS is the cleavage of dimethylsulfoniopropionate (DMSP), which can be produced by marine bacteria and phytoplankton. Polar oceans, which represent about one fifth of Earth's surface, contribute significantly to the global oceanic DMS sea-air flux. However, a global overview of DMS and DMSP cycling in polar oceans is still lacking and the key genes and the microbial assemblages involved in DMSP/DMS transformation remain to be fully unveiled. RESULTS: Here, we systematically investigated the biogeographic traits of 16 key microbial enzymes involved in DMS/DMSP cycling in 60 metagenomic samples from polar waters, together with 174 metagenome and 151 metatranscriptomes from non-polar Tara Ocean dataset. Our analyses suggest that intense DMS/DMSP cycling occurs in the polar oceans. DMSP demethylase (DmdA), DMSP lyases (DddD, DddP, and DddK), and trimethylamine monooxygenase (Tmm, which oxidizes DMS to dimethylsulfoxide) were the most prevalent bacterial genes involved in global DMS/DMSP cycling. Alphaproteobacteria (Pelagibacterales) and Gammaproteobacteria appear to play prominent roles in DMS/DMSP cycling in polar oceans. The phenomenon that multiple DMS/DMSP cycling genes co-occurred in the same bacterial genome was also observed in metagenome assembled genomes (MAGs) from polar oceans. The microbial assemblages from the polar oceans were significantly correlated with water depth rather than geographic distance, suggesting the differences of habitats between surface and deep waters rather than dispersal limitation are the key factors shaping microbial assemblages involved in DMS/DMSP cycling in polar oceans. CONCLUSIONS: Overall, this study provides a global overview of the biogeographic traits of known bacterial genes involved in DMS/DMSP cycling from the Arctic and Antarctic oceans, laying a solid foundation for further studies of DMS/DMSP cycling in polar ocean microbiome at the enzymatic, metabolic, and processual levels. Video Abstract.

2.
Microbiol Spectr ; : e0046321, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643440

RESUMO

Alteromonas is a ubiquitous, abundant, copiotrophic and phytoplankton-associated marine member of the Gammaproteobacteria with a range extending from tropical waters to polar regions and including hadal zones. Here, we describe a novel Alteromonas phage, ZP6, that was isolated from surface coastal waters of Qingdao, China. ZP6 contains a linear, double-stranded, 38,080-bp DNA molecule with 50.1% G+C content and 47 putative open reading frames (ORFs). Three auxiliary metabolic genes were identified, encoding metal-dependent phosphohydrolase, diaminopurine synthetase, and nucleotide pyrophosphohydrolase. The first two ORFs facilitate the replacement of adenine (A) by diaminopurine (Z) in phage genomes and help phages to evade attack from host restriction enzymes. The nucleotide pyrophosphohydrolase enables the host cells to stop programmed cell death and improves the survival rate of the host in a nutrient-depleted environment. Phylogenetic analysis based on the amino acid sequences of whole genomes and comparative genomic analysis revealed that ZP6 is most closely related to Enhodamvirus but with low similarity (shared genes, <30%, and average nucleotide sequence identity, <65%); it is distinct from other bacteriophages. Together, these results suggest that ZP6 could represent a novel viral genus, here named Mareflavirus. Combining its ability to infect Alteromonas, its harboring of a diaminopurine genome-biosynthetic system, and its representativeness of an understudied viral group, ZP6 could be an important and novel model system for marine virus research. IMPORTANCE Alteromonas is an important symbiotic bacterium of phytoplankton, but research on its bacteriophages is still at an elementary level. Our isolation and genome characterization of a novel Alteromonas podovirus, ZP6, identified a new viral genus of podovirus, namely, Mareflavirus. The ZP6 genome, with a diaminopurine genome-biosynthetic system, is different from those of other isolated Alteromonas phages and will bring new impetus to the development of virus classification and provide important insights into novel viral sequences from metagenomic data sets.

3.
Appl Environ Microbiol ; : AEM0116021, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469192

RESUMO

Nordic Seas are the subarctic seas connecting the Arctic Ocean and North Atlantic Ocean with complex water masses, experiencing an abrupt climate change. Though the knowledge of the marine virosphere has been expanded rapidly, the diversity of viruses and their relationships with host cells and water masses in the Nordic Seas remains to be fully revealed. Here we establish the Nordic Seas DNA viromes (NSVs) dataset of 55,315 viral contigs including 1,478 unique viral populations from seven stations influenced by both the warm Atlantic and cold Arctic water masses. Caudovirales dominated in the seven NSVs, especially in the warm Atlantic waters. The major giant nucleocytoplasmic large DNA viruses (NCLDVs) contributed a significant proportion of the classified viral contigs in the NSVs (32.2%), especially in the cold Arctic waters (44.9%). The distribution patterns of Caudovirales and NCLDVs were a reflection of the community structure of their hosts in the corresponding water masses and currents. Latitude, pH, and flow speed were found to be key factors influencing the microbial communities and co-influencing the variation of viral communities. Network analysis illustrated the tight coupling between the variation of viral communities and microbial communities in the Nordic Seas. This study suggests a probable linkage between the viromes, host cells and the surface water masses from both the cool Arctic and warm Atlantic Oceans. Importance: This is a systematic study of Nordic Seas Viromes using metagenomic analysis. The viral diversity, community structure, and their relationships with host cells and the complex water masses from both the cool Arctic and warm Atlantic Oceans were illustrated. The NCLDVs and Caudovirales are proposed as the viral characteristics of the cold Arctic and the warm Atlantic waters, respectively. This study provided an important background for the viromes in the subarctic seas connecting the Arctic Ocean and North Atlantic Ocean, and will shed a light on their responses to the abrupt climate change in the future.

4.
J Neurosurg ; : 1-8, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479209

RESUMO

OBJECTIVE: MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive alternative for medication-refractory tremor in Parkinson's disease (PD). However, the impact of MRgFUS thalamotomy on spontaneous neuronal activity in PD remains unclear. The purpose of the current study was to evaluate the effects of MRgFUS thalamotomy on local fluctuations in neuronal activity as measured by the fractional amplitude of low-frequency fluctuations (fALFF) in patients with PD. METHODS: Participants with PD undergoing MRgFUS thalamotomy were recruited. Tremor scores were assessed before and 3 and 12 months after treatment using the Clinical Rating Scale for Tremor. MRI data were collected before and 1 day, 1 week, 1 month, 3 months, and 12 months after thalamotomy. The fALFF was calculated. A whole-brain voxel-wise paired t-test was used to identify significant changes in fALFF at 12 months after treatment compared to baseline. Then fALFF in the regions with significant differences were extracted from fALFF maps of patients for further one-way repeated-measures ANOVA to investigate its dynamic alterations. The association between fALFF changes induced by thalamotomy and tremor improvement were evaluated using the nonparametric Spearman rank test. RESULTS: Nine participants with PD (mean age ± SD 64.7 ± 6.1 years, 8 males) were evaluated. Voxel-based analysis showed that fALFF in the left occipital cortex (Brodmann area 17 [BA17]) significantly decreased at 12 months after thalamotomy compared to baseline (voxel p < 0.001, cluster p < 0.05 family-wise error [FWE] corrected). At baseline, fALFF in the left occipital BA17 in patients was elevated compared with that in 9 age- and gender-matched healthy subjects (p < 0.05). Longitudinal analysis displayed the dynamic changes of fALFF in this region (F (5,40) = 3.61, p = 0.009). There was a significant positive correlation between the falling trend in fALFF in the left occipital BA17 and hand tremor improvement after treatment over 3 time points (Spearman's rho = 0.44, p = 0.02). CONCLUSIONS: The present study investigated the impact of MRgFUS ventral intermediate nucleus thalamotomy on spontaneous neural activity in medication-refractory tremor-dominant PD. The visual area is, for the first time, reported as relevant to tremor improvement in PD after MRgFUS thalamotomy, suggesting a distant effect of MRgFUS thalamotomy and the involvement of specific visuomotor networks in tremor control in PD.

5.
Nat Commun ; 12(1): 5416, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518544

RESUMO

Hypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with LUBAC, the linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.

6.
Medicine (Baltimore) ; 100(34): e27123, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449517

RESUMO

ABSTRACT: The specific method and dose of tranexamic acid (TXA) topically applied for intertrochanteric fractures have not been well established. The aim of this study is to investigate the efficacy and safety of TXA topically administered via our protocol for perioperative bleeding management in elderly patients with intertrochanteric fractures who underwent proximal femoral nail anti-rotation (PFNA).A retrospective comparative analysis was performed. The TXA group was composed of 82 patients with topical use of TXA, and the control group was composed of 82 patients without TXA use during the PFNA procedure. Intraoperative, total and hidden amounts of blood loss, drainage volumes, postoperative blood transfusion volumes and complications were compared between the 2 groups.The intraoperative, total and hidden amounts of blood loss and the drainage volumes were significantly lower in the TXA group than in the control group (P = .012, P < .01, P < .01, P = .014, respectively). The volume and rate of blood transfusion in the TXA group were significantly lower than those in the control group (P < .01). There were no significant differences in complications between the 2 groups (P > .05).Topical application of TXA offers an effective and safe option for reducing perioperative blood loss and transfusion in elderly patients with intertrochanteric fractures undergoing PFNA.


Assuntos
Antifibrinolíticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Ácido Tranexâmico/administração & dosagem , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
7.
Sci Rep ; 11(1): 17178, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433839

RESUMO

Obstructive sleep apnea (OSA) is a common sleep respiratory disease. Previous studies have found that the wakefulness electroencephalogram (EEG) of OSA patients has changed, such as increased EEG power. However, whether the microstates reflecting the transient state of the brain is abnormal is unclear during obstructive hypopnea (OH). We investigated the microstates of sleep EEG in 100 OSA patients. Then correlation analysis was carried out between microstate parameters and EEG markers of sleep disturbance, such as power spectrum, sample entropy and detrended fluctuation analysis (DFA). OSA_OH patients showed that the microstate C increased presence and the microstate D decreased presence compared to OSA_withoutOH patients and controls. The fifth microstate E appeared during N1-OH, but the probability of other microstates transferring to microstate E was small. According to the correlation analysis, OSA_OH patients in N1-OH showed that the microstate D was positively correlated with delta power, and negatively correlated with beta and alpha power; the transition probability of the microstate B → C and E → C was positively correlated with alpha power. In other sleep stages, the microstate parameters were not correlated with power, sample entropy and FDA. We might interpret that the abnormal transition of brain active areas of OSA patients in N1-OH stage leads to abnormal microstates, which might be related to the change of alpha activity in the cortex.

8.
Chin Med J (Engl) ; 134(16): 1967-1976, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34310400

RESUMO

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).


Assuntos
COVID-19 , Idoso , Anticorpos Antivirais , COVID-19/terapia , Vacinas contra COVID-19 , Método Duplo-Cego , Humanos , Imunização Passiva , Proteínas Recombinantes de Fusão , SARS-CoV-2
9.
Emerg Microbes Infect ; 10(1): 1589-1597, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34197281

RESUMO

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase I clinical trials in humans. A Randomized, double-blind, placebo-controlled Phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive the vaccine (10, 25, and 50 µg) or placebo (V-01: Placebo = 4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed a promising safety profile with approximately 25% vaccine-related overall adverse events (AEs) within 30 days and no grade 3 or worse AEs. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10 µg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in Phase II/III clinical trials.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Interferons/imunologia , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , China , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina G/sangue , Interferons/administração & dosagem , Interferons/genética , Masculino , Pessoa de Meia-Idade , Placebos , Vacinação/efeitos adversos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Adulto Jovem
10.
Jpn J Radiol ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34076855

RESUMO

PURPOSE: PET enables a concurrent evaluation of perfusion status and metabolic activity. We aimed to evaluate the feasibility of perfusion and early-uptake 18F-FDG PET/CT in hepatocellular carcinoma (HCC) using a dual-input dual-compartment uptake model. MATERIALS AND METHODS: Data from 5 min dynamic PET/CT and conventional PET/CT scans were retrospectively collected from 17 pathologically diagnosed HCCs. Parameters such as hepatic arterial blood flow (Fa), portal vein blood flow (Fv), total blood flow (F), hepatic arterial perfusion index (HPI), portal vein perfusion index (PPI), blood volume (BV), extracellular mean transit time (MTT) and intracellular uptake rate (Ki) were calculated. Fa, HPI, MTT and Ki images were generated and used to identify HCC. RESULTS: Compared with the surrounding liver tissue, HCCs showed significant increases in Fa, HPI, Ki and the maximum standard uptake value (SUVmax) (all P < 0.001) and significant reductions in Fv (P < 0.05) and PPI (P < 0.001). F, BV and MTT (all P > 0.05) did not differ significantly between HCCs and the surrounding liver tissue. Perfusion and early-uptake PET/CT increased the positivity rate of HCCs from 52.9% with conventional PET/CT alone to 88.2% with the combined method (P < 0.05). CONCLUSIONS: Perfusion and early-uptake PET/CT are feasible for diagnosing HCC and provide added functional information to enhance diagnostic performance.

11.
J Cell Biol ; 220(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33988695

RESUMO

Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Cálcio/metabolismo , Calmodulina/metabolismo , Espinhas Dendríticas/fisiologia , Plasticidade Neuronal , Neurônios/fisiologia , Sinapses/fisiologia , Animais , Calmodulina/genética , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/citologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33961558

RESUMO

To establish robust semantic correspondence between images covering different objects belonging to the same category, there are three important types of information including inter-image relationship, intra-image relationship and cycle consistency. Most existing methods only exploit one or two types of the above information and cannot make them enhance and complement each other. Different from existing methods, we propose a novel end-to-end Consistency Graph Modeling Network (CGMNet) for semantic correspondence by modeling inter-image relationship, intra-image relationship and cycle consistency jointly in a unified deep model. The proposed CGMNet enjoys several merits. First, to the best of our knowledge, this is the first work to jointly model the three kinds of information in a deep model for semantic correspondence. Second, our model has designed three effective modules including cross-graph module, intra-graph module and cycle consistency module, which can jointly learn more discriminative feature representations robust to local ambiguities and background clutter for semantic correspondence. Extensive experimental results show that our algorithm performs favorably against state-of-the-art methods on four challenging datasets including PF-PASCAL, PF-WILLOW, Caltech-101 and TSS.

13.
Extremophiles ; 25(3): 235-248, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33938982

RESUMO

Picoeukaryotes constitute an important component of the living biomass of oceanic communities and play major roles in biogeochemical cycles. There are very few studies on picoeukaryotes found in the Chukchi Sea. This work shows the relationship between community distribution and composition of picoeukaryotes residing in water masses and physicochemical factors in the southern Chukchi Sea studied in both midsummer (July) and early autumn (September), 2012. Illumina 18S V4 rDNA metabarcoding were used as the main tool. In July, Mamiellophyceae, Dinophyceae, and Trebouxiophyceae were the main microbial classes, with Micromonas, Prasinoderma, Telonema, Amoebophrya, Bathycoccus, Picomonas, and Bolidomonas representing the main genera. In September, Trebouxiophyceae surpassed Dinophyceae and was the second main microbial class, with Micromonas, Prasinoderma, Bathycoccus, Bolidomonas, Telonema, Choricystis, and Diaphanoeca representing the main genera. Water mass was the primary factor determining the community composition and diversity of picoeukaryotes. Abundance of Bathycoccus was found to be highly correlated with Alaskan Coastal Water and that of Prasinoderma, Bolidomonas, and Diaphanoeca with Bering Seawater. Nitrate and phosphate content of water in midsummer and dissolved oxygen (DO) and temperature in early autumn were the main factors that shaped the abundance of the picoeukaryote community.


Assuntos
Clorófitas , Água do Mar , Clorófitas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Oceanos e Mares , Estações do Ano
14.
Arch Virol ; 166(6): 1653-1659, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33796884

RESUMO

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.


Assuntos
Enterovirus Humano A , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , China/epidemiologia , Genótipo , Humanos , Incidência , Epidemiologia Molecular , Filogenia , Estudos Retrospectivos
15.
Water Res ; 196: 116990, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33725645

RESUMO

Noroviruses (NoVs) are the leading cause of acute gastroenteritis (AGE) outbreaks. Since 2014, novel genetic variants of NoV have been continuously identified and have caused a sharp increase in the number of AGE outbreaks. The specific geographical distribution and expanding genetic diversity of NoV has posed a challenge to conventional surveillance. Here, we describe the long-term dynamic correlation between NoV distribution in sewage and in the local population through the molecular surveillance of NoV in Guangdong, 2013-2018. The relative viral loads of the GI and GII genotypes in sewage were calculated through RT-PCR. A high-throughput sequencing method and operational taxonomic unit (OTU) clustering pipeline were developed to illustrate the abundances of different genotypes and genetic variants in sewage. Our results showed that the NoV viral loads and the emergence of new variants in sewage were closely associated with NoV outbreak risks in the population. Compared with the outbreaks surveillance, the dominance of the newly emerged variants, GII.P17-GII.17 and GII.P16-GII.2, could be detected one or two months ahead in sewage of a hub city. In addition, the dynamics of pre-epidemic variants, which were rarely detected in clinics, could be captured through sewage surveillance, thus improving our understanding of the origin and evolution of these novel epidemic variants. Our data highlight that sewage surveillance could provide nearly real-time and high-throughput data on NoV circulation in the community. With the advances in sequencing techniques, the sewage surveillance system could also be extended to other related infectious diseases.


Assuntos
Infecções por Caliciviridae , Norovirus , Infecções por Caliciviridae/epidemiologia , China/epidemiologia , Cidades , Surtos de Doenças , Genótipo , Humanos , Norovirus/genética , Filogenia , Esgotos
16.
Curr Pharm Des ; 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33781189

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an acute or subacute demyelinating disease that affects mainly the optic nerve and spinal cord. A major proportion of NMOSD cases have a relationship with autoimmunity to aquaporin 4 (AQP4) found on the central nervous system. NMOSD can occur repeatedly, causing symptoms such as decreased vision and weakness of limbs. The main goal of current therapy is to relieve acute symptoms and prevent recurrence of the disease. Without timely and appropriate treatment, the recurrence and disability rates are high. In the present work, we review recent advances in the diagnosis and treatment of patients with NMOSD, as well as the pathogenesis and mechanisms of AQP4-IgG-seropositive NMOSD.

17.
J Cell Biol ; 220(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33533934

RESUMO

The centrosome is the main microtubule-organizing center in animal cells. It comprises of two centrioles and the surrounding pericentriolar material. Protein organization at the outer layer of the centriole and outward has been studied extensively; however, an overall picture of the protein architecture at the centriole core has been missing. Here we report a direct view of Drosophila centriolar proteins at ∼50-nm resolution. This reveals a Sas6 ring at the C-terminus, where it overlaps with the C-terminus of Cep135. The ninefold symmetrical pattern of Cep135 is further conveyed through Ana1-Asterless axes that extend past the microtubule wall from between the blades. Ana3 and Rcd4, whose termini are close to Cep135, are arranged in ninefold symmetry that does not match the above axes. During centriole biogenesis, Ana3 and Rcd4 are sequentially loaded on the newly formed centriole and are required for centriole-to-centrosome conversion through recruiting the Cep135-Ana1-Asterless complex. Together, our results provide a spatiotemporal map of the centriole core and implications of how the structure might be built.


Assuntos
Centríolos/metabolismo , Centríolos/ultraestrutura , Animais , Linhagem Celular , Centríolos/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Domínios Proteicos
18.
Virus Res ; 295: 198265, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33550041

RESUMO

Although Pseudoalteromonas is an abundant, ubiquitous, marine algae-associated bacterial genus, there is still little information on their phages. In the present study, a marine phage AL, infecting Pseudoalteromonas marina, was isolated from the coastal waters off Qingdao. The AL phage is a siphovirus with an icosahedral head of 53 ± 1 nm and a non-contractile tail, length of 99 ± 1 nm. A one-step growth curve showed that the latent period was approximately 70 min, the rise period was 50 min, and the burst size was 227 pfu/cell. The genome sequence of this phage is a 33,582 bp double-stranded DNA molecule with a GC content of 40.1 %, encoding 52 open reading frames (ORFs). The order of the functional genes, especially those related to the structure module, is highly conserved and basically follows the common pattern used by siphovirus. The stable order has been formed during the long-term evolution of phages in the siphovirus group, which has helped the phages to maintain their normal morphology and function. Phylogenetic trees based on the major capsid protein (mcp) and genome-wide sequence have shown that the AL phage is closely related to four Pseudoalteromonas phages, including PHS21, PHS3, SL25 and Pq0. Further analysis using all-to-all BLASTP also confirmed that this phage shared high sequence homology with the same four Pseudoalteromonas phages, with amino acid sequence identities ranging from 44 % to 71 %. In particular, their similarity in virion structure module may imply that these phages share common assembly mechanism characteristics and infection pathways. Pseudoalteromonas phage AL not only provides basic information for the further study of the evolution of Pseudoalteromonas phages and interactions between marine phage and host but also helps to explain the unknown viral sequences in the metagenomic databases.

19.
J Sep Sci ; 44(12): 2465-2473, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32367689

RESUMO

A facile strategy based on the boronate affinity and polydopamine coating was proposed for the preparation of surface molecularly imprinted polymer microspheres using naringin as the glycoside template. The poly(methacrylic acid-co-methyl methacrylate-co-ethyleneglycol dimethacrylate) microspheres were firstly synthesized as inner cores by suspension polymerization method, and then functionalized with 3-aminophenylboronic acid. The imprinted shell layer was obtained by self-polymerization of dopamine on the surface of boronic acid-functionalized polymer microspheres after reversible immobilization of naringin. The resultant surface molecularly imprinted microspheres showed good imprinting efficiency and recognition specificity toward the template molecule in aqueous environment. The isothermal and kinetic adsorption behaviors of the polymers were investigated. The results showed that the covalent surface imprinted microspheres possessed homogeneous recognition sites, strong adsorption affinity, and rapid rebinding kinetics. In addition, the surface imprinted microspheres were utilized as the sorbents of solid phase extraction to successfully separate and enrich naringin from Citri Grandis extract, and the recovery of naringin in eluting solution reached 84.4%.

20.
Mol Oncol ; 15(1): 279-298, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33155366

RESUMO

Deubiquitinase BAP1 is an important tumor suppressor in several malignancies, but its functions and critical substrates in prostate cancer (PCa) remain unclear. Here, we report that the mRNA and protein expression levels of BAP1 are downregulated in clinical PCa specimens. BAP1 can physically bind to and deubiquitinate PTEN, which inhibits the ubiquitination-mediated degradation of PTEN and thus stabilizes PTEN protein. Ectopically expressed BAP1 in PCa cells increases PTEN protein level and subsequently inhibits the AKT signaling pathway, thus suppressing PCa progression. Conversely, knockdown of BAP1 in PCa cells leads to the decrease in PTEN protein level and the activation of the Akt signaling pathway, therefore promoting malignant transformation and cancer metastasis. However, these can be reversed by the re-expression of PTEN. More importantly, we found that BAP1 protein level positively correlates with PTEN in a substantial fraction of human cancers. These findings demonstrate that BAP1 is an important deubiquitinase of PTEN for its stability and the BAP1-PTEN signaling axis plays a crucial role in tumor suppression.

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