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Some tropical sea cucumbers of the family Holothuriidae can efficiently repel or even fatally ensnare predators by sacrificially ejecting a bioadhesive matrix termed the Cuvierian organ (CO), so named by the French zoologist Georges Cuvier who first described it in 1831. Still, the precise mechanisms for how adhesiveness genetically arose in CO and how sea cucumbers perceive and transduce danger signals for CO expulsion during defense have remained unclear. Here, we report the first high-quality, chromosome-level genome assembly of Holothuria leucospilota , an ecologically significant sea cucumber with prototypical CO. The H. leucospilota genome reveals characteristic long-repeat signatures in CO-specific outer-layer proteins, analogous to fibrous proteins of disparate species origins, including spider spidroin and silkworm fibroin. Intriguingly, several CO-specific proteins occur with amyloid-like patterns featuring extensive intramolecular cross- β structures readily stainable by amyloid indicator dyes. Distinct proteins within the CO connective tissue and outer surface cooperate to give the expelled matrix its apparent tenacity and adhesiveness, respectively. Genomic evidence offers further hints that H. leucospilota directly transduces predator-induced mechanical pressure onto the CO surface through mediation by transient receptor potential channels, which culminates in acetylcholine-triggered CO expulsion in part or in entirety. Evolutionarily, innovative events in two distinct regions of the H. leucospilota genome have apparently spurred CO’s differentiation from the respiratory tree to a lethal defensive organ against predators.

In food processing environments, various microorganisms can adhere and aggregate on the surface of equipment, resulting in the formation of multispecies biofilms. Complex interactions among microorganisms may affect the formation of multispecies biofilms and resistance to disinfectants, which are food safety and quality concerns. This article reviews the various interactions among microorganisms in multispecies biofilms, including competitive, cooperative, and neutral interactions. Then, the preliminary mechanisms underlying the formation of multispecies biofilms are discussed in relation to factors, such as quorum-sensing signal molecules, extracellular polymeric substances, and biofilm-regulated genes. Finally, the resistance mechanisms of common contaminating microorganisms to disinfectants in food processing environments are also summarized. This review is expected to facilitate a better understanding of interspecies interactions and provide some implications for the control of multispecies biofilms in food processing. HIGHLIGHTS

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a mortal threat to human health. The elucidation of the relationship between peripheral immune cells and the development of inflammation is essential for revealing the pathogenic mechanism of COVID-19 and developing related antiviral drugs. The immune cell metabolism-targeting therapies exhibit a desirable anti-inflammatory effect in some treatment cases. In this study, based on differentially expressed gene (DEG) analysis, a genome-scale metabolic model (GSMM) was reconstructed by integrating transcriptome data to characterize the adaptive metabolic changes in peripheral blood mononuclear cells (PBMCs) in severe COVID-19 patients. Differential flux analysis revealed that metabolic changes such as enhanced aerobic glycolysis, impaired oxidative phosphorylation, fluctuating biogenesis of lipids, vitamins (folate and retinol), and nucleotides played important roles in the inflammation adaptation of PBMCs. Moreover, the main metabolic enzymes such as the solute carrier (SLC) family 2 member 3 (SLC2A3) and fatty acid synthase (FASN), responsible for the reactions with large differential fluxes, were identified as potential therapeutic targets. Our results revealed the inflammation regulation potentials of partial metabolic reactions with differential fluxes and their metabolites. This study provides a reference for developing potential PBMC metabolism-targeting therapy strategies against COVID-19.

Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

Objective: To compare the efficacy of the traditional Chinese medicine SanJieZhenTong (SJZT) capsules versus gonadotropin-releasing hormone analogs (GnRHa) or oral contraceptives (OCs) in the postoperative treatment of moderate-to-severe endometriosis. Methods: In this prospective clinical trial, women with stage III–IV endometriosis according to the revised American Fertility Society scoring system received three doses of GnRHa immediately after laparoscopic conservative surgery, followed by random assignment to receive treatment with SJZT, GnRHa, or OCs for another 6 months. The primary endpoint was 2-year recurrence, and the secondary endpoints were adverse events, changes in physical function, and quality of life (QoL). Recurrence was assessed using Kaplan–Meier curves and log-rank tests. Generalized estimating equations were used to determine the parameters of the secondary endpoints. Results: A total of 66 women were randomly assigned to the SJZT (n = 21), GnRHa (n = 21), and OCs (n = 24) groups. At a median follow-up of 22 months, no difference in recurrence was found (P = 0.72), with one (4.8%), two (9.5%), and one (4.2%) incidence in the SJZT, GnRHa, and OCs groups, respectively. Expectedly, the incidence of side effects such as hot flush, insomnia, and arthralgia in the SJZT and OCs groups was significantly lower than that in the GnRHa group (P = 0.00). In addition, the female sexual function index was significantly improved in the SJZT group, with a higher value than that in the GnRHa (odds ratio [OR] = 5.25, 95% confidence interval [CI]: 2.09–13.14, P = 0.00) and OCs (OR = 3.94, 95% CI: 1.58–9.83, P = 0.00) groups. Conclusions: SJZT showed more effective pain relief and QoL improvement in patients with moderate-to-severe endometriosis than GnRHa or OCs did. Fewer adverse events than those observed with other agents indicate that this alternative medicine, SJZT, could be a novel option for the long-term management of endometriosis.

In birds, vitelline membrane outer layer protein 1 (VMO1) is an exogenous protein that can be absorbed by eggs as a barrier to prevent the mixing of yolk and egg white. However, researches on VMO1 are limited in birds but not other non-avian species until now. In this study, we first identified a novel Vmo1 cDNA (Lv-Vmo1) in Pacific white shrimp (Litopenaeus vannamei), the most important cultured shrimp in the world. We further analyzed its gene organization, phylogenetic relationship and protein structure. The Lv-Vmo1 transcript was specifically expressed in the hepatopancreas without sexual dimorphism. During ovarian development in female, the hepatopancreatic Lv-Vmo1 mRNA levels showed a significant increase. By in situ hybridization, Lv-Vmo1 mRNA was present in three cell types of the hepatopancreas but neither oocytes nor follicle cells of the ovary. In contrast, immunofluorescence revealed that Lv-VMO1 protein was distributed in the cytoplasms of both hepatopancreatic cells and ovarian oocytes. Western blot showed that Lv-VMO1 protein was produced in the hepatopancreas and transported to the ovary via hemolymph circulation. Identification of a species-specific egg-entry guide protein is the key to the receptor-mediated ovarian transduction of cargo, a novel gene editing approach in oviparous animals. This study lays the mechanism for exogenous transport into penaeid shrimp eggs by VMO1, as a foundation for achieving exogenous protein-mediated incorporation into oocytes.

Salmonella enterica is a prominent foodborne pathogen, including diverse serotypes that are prolific biofilm formers. Its ability to form biofilm can be affected by multiple environmental factors. In this study, the effect of salinity on biofilm formation by S. enterica was evaluated by using two recently isolated strains of Salmonella serotypes Enteritidis and Newport. Although supplementing the growth medium with a low concentration (0.5 to 2%) of sodium chloride (NaCl) slightly enhanced biofilm formation for the strain S. enterica serovar Enteritidis 110, it sharply reduced or abolished biofilm formation by the strain S. enterica serovar Newport 193. This differential effect of salinity on S. enterica strains of different serotypes was poorly correlated with inhibition of planktonic growth but strongly correlated with cell motility. Examining genes known to affect biofilm formation showed that the expression of adrA, csgD, and fliC, which encode proteins required for surface adhesion and cell motility, was significantly downregulated with salinity increase in Salmonella Newport 193 but not in Salmonella Enteritidis 110. Therefore, it is plausible that the differential effect of salinity on biofilm formation by Salmonella Enteritidis 110 and Salmonella Newport 193 resulted from the differential regulation to genes required for cell adherence and motility.

A fluorescence immunoassay has been widely applied in different fields due to its high sensitivity, simple operations, and high accuracy. Quantum dots (QDs) are often selected as labels in a fluorescence immunoassay due to their high fluorescence, better stability, and biocompatibility. In this study, novel doped CdTe : Zn/ZnS QDs with stability and a high photoluminescence quantum yield (40.78%) were prepared by the water synthesis method and used as labels to conjugate with goat anti-rabbit IgG to establish a fluorescence immunoassay (FLISA) for bacteria compared to the traditional enzyme-linked immunosorbent assay (ELISA) based on the reaction between an antibody and an antigen. A good linear relationship between the fluorescence intensity and concentrations of D. tsuruhatensis CM13 was found when the concentrations were in the range of 103 CFU mL−1–108 CFU mL−1. The limit of detection (LOD) of D. tsuruhatensis CM13 was 1.25 × 103 CFU mL−1 by FLISA, which was about 80 times lower than the LOD obtained from ELISA (105 CFU mL−1). This indicated that our FLISA method has higher sensitivity than traditional ELISA, and the CdTe : Zn/ZnS QDs synthesized in this paper have good applications in the rapid sensitive detection of microorganisms.

Circular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor‐suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor‐suppressive roles in various cancers, including liver cancer (circARSP91, circADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA‐3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor‐suppressive circRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs., Tumor‐suppressive circRNAs may be used as potential and potent therapeutic targets. Moreover, we can propose a new method for the classification of circRNAs: based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs.

Background As far as gastric cancer is concerned, there is a lack of specific early diagnostic biomarkers in clinical diagnosis. Circular RNAs (circRNAs) have been found to be stable in gastric cancer tissues and plasma, so they have the potential to become new type of diagnostic biomarkers for gastric cancer. Materials and Methods The hsa_circ_0001811 expressions in gastric cancer tissues and paired non‐cancer tissues, preoperative and postoperative plasma of patients with gastric cancer, and plasma of healthy volunteers were detected using quantitative reverse transcription‐polymerase chain reaction. The receiver operating characteristic (ROC) curves were drawn; and the combined ROC curves were used to analyze their diagnostic values. The correlation between the plasma or tissue hsa_circ_0001811 levels and the clinicopathological factors of gastric cancer was further analyzed. Results Hsa_circ_0001811 was found to be lowly expressed in gastric cancer tissues and plasma from patients with gastric cancer. The area under the ROC curve (AUC) in the gastric cancer tissues and the plasma of patients with gastric cancer was 0.658 and 0.747, respectively. The AUC increased to 0.824 after combination of both. The expression level of hsa_circ_0001811 in gastric cancer tissue correlated with carcinoembryonic antigen (CEA) (P = .0347), tissue differentiation (P = .0138), and lymph node metastasis (P = .0234), while plasma hsa_circ_0001811 level was related to carbohydrate antigen (CA19‐9) (P = .0278), lymph node metastasis (P = .0469), distant metastasis (P = .0384), and age (P = .0085). Conclusions The above results indicate that hsa_circ_0001811 may become a new biomarker for clinical diagnosis of gastric cancer., Sanger sequence results of qRT‐PCR products of hsa_circ_0001811 are consistent with the sequence of target circRNA. Compared with paired non‐cancer tissues, hsa_circ_0001811 was low expressed in gastric cancer tissues (2A); and the expression of plasma specimens one day before surgery in gastric cancer patients was lower, then those in ten days after surgery and plasma samples of healthy volunteers (2B). The AUC of hsa_circ_0001811 in gastric cancer tissues was 0.658, while the AUC in plasma was 0.747. When tissues and plasma were combined used, the AUC increased to 0.824, further showing the higher diagnostic value of hsa_circ_0001811.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been found to play important roles in the occurrence and development of cancers. However, the tsRNA profile in gastric cancer is unknown. In this study, we aimed to identify the global tsRNA profile in plasma from gastric cancer patients and elucidate the role of tRF-33-P4R8YP9LON4VDP in gastric cancer. Differentially expressed tsRNAs in the plasma of gastric cancer patients and healthy controls were investigated using RNA sequencing. The expression levels of tRF-33-P4R8YP9LON4VDP in the plasma of gastric cancer patients, healthy controls and gastric cancer cell lines were first detected by quantitative reverse transcription-polymerase chain reaction. The effects of tRF-33-P4R8YP9LON4VDP overexpression or downregulation in gastric cancer cells on proliferation, migration, apoptosis, and cell cycle were analyzed using the Cell Counting Kit‐8, scratch assay, Transwell assay, and flow cytometry, respectively. There were 21 upregulated and 46 downregulated tsRNAs found in plasma from gastric cancer patients. The significantly upregulated tsRNAs included tRF-18-S3M83004, tRF-31-PNR8YP9LON4VD, tRF-19-3L7L73JD, tRF-33-P4R8YP9LON4VDP, tRF-31-PER8YP9LON4VD, tRF-18-MBQ4NKDJ, and tRF-31-PIR8YP9LON4VD. The significantly downregulated tsRNAs included tRF-41-YDLBRY73W0K5KKOVD, tRF-18-07QSNHD2, tRF-28-86J8WPMN1E0J, tRF-29-86V8WPMN1EJ3, tRF-31-6978WPRLXN4VE, tRF-30-MIF91SS2P46I, tRF-26-MI7O3B1NR8E, tRF-30-RRJ89O9NF5W8, tRF-26-XIP2801MK8E, and tRF-35-V0J8O9YEKPRS93, In vitro studies showed that tRF-33-P4R8YP9LON4VDP inhibited proliferation of gastric cancer cells. In conclusion, tsRNAs such as tRF-33-P4R8YP9LON4VDP could serve as a novel diagnostic biomarker and target for gastric cancer therapeutics.

Objective: To investigate factors that may be associated with the recurrence of deep infiltrating endometriosis (DIE) and DIE-related symptoms. Methods: Starting in September 2014, women with a confirmed diagnosis of DIE based on surgical and histological findings were included in the prospective study with a 2-year follow-up in our hospital. A total of 84 consecutive patients were included, all of whom underwent laparoscopic surgery. The data were obtained from the medical records of the patients. Follow-up data, including presence of pain as assessed using the visual analog scale (VAS) score and ultrasonography/magnetic resonance imaging findings, were obtained at 3, 6, 9, 12, and 24 months postoperatively. Variables, such as age, body mass index, severity and duration of symptoms, size and location of the lesion, and pre- and postoperative medical treatment, were evaluated using univariate and multivariate analyses to identify factors correlated to recurrence. Results: A total of 11 (13.1%) patients presented with recurrence, with a mean time to recurrence of 14.2 months. The univariate analysis showed that the longer duration of menstruation (7.4 vs. 6.0, P = 0.010), the more advanced revised American Fertility Society (rAFS) stage (Stages I and II vs. III and IV, χ2 = 9.964, P = 0.001), the higher VAS score for dysmenorrhea (9.4 vs. 5.2, P = 0.001), and the more severe pain during defecation (7.8 vs. 4.8, P = 0.016) were positively correlated to DIE recurrence. However, the multivariate analysis also revealed that a more severe dysmenorrhea and advanced rAFS stage were the independent factors associated with the recurrence of DIE, with an odds ratio of 1.895 (confidence interval [CI]: 1.061–3.385, P = 0.031) and 4.310 (CI: 1.091–17.028, P = 0.037), respectively. Conclusions: More than 10% of patients presented with recurrence of DIE 2 years after surgery. Recurrence of DIE was more common in patients who complained of more severe dysmenorrhea and had an advanced rAFS stage.

Trehalases are a group of enzymes that catalyse the conversion of trehalose to glucose, and they are observed in most organisms. In this study, the first echinoderm trehalase, designated Hl-Tre, was identified from a tropical sea cucumber, Holothuria leucospilota. The full-length cDNA of H. leucospilota trehalase (Hl-Tre) is 2461 bp in length with an open reading frame (ORF) of 1788 bp that encodes a 595-amino-acid protein with a deduced molecular weight of 67.95 KDa. The Hl-Tre protein contains a signal peptide at the N-terminal and a functional trehalase domain, which includes the signature motifs 1 and 2. The mRNA expression of Hl-Tre was ubiquitously detected in all selected tissues, with the highest level being detected in the intestine. By in situ hybridization (ISH), the positive Hl-Tre signals were observed in the brush borders of the intestinal mucosa. In embryonic and larval stages, the transcript levels of Hl-Tre decreased during embryonic development and increased after the pentactula stage. After a challenge of starvation, the intestinal Hl-Tre mRNA levels were observed to be first decreased and partially recovered thereafter. Overall, our study provided the first evidence for trehalase in echinoderms and showed that this enzyme was potentially linked to a trehalose metabolic pathway in sea cucumbers.

To ascertain the trends and burden of malaria in China and the costs of interventions for 2011-2015.We analysed the spatiotemporal and demographic features of locally transmitted and imported malaria cases using disaggregated surveillance data on malaria from 2011 to 2015, covering the range of dominant malaria vectors in China. The total and mean costs for malaria elimination were calculated by funding sources, interventions and population at risk.A total of 17 745 malaria cases, including 123 deaths (0.7%), were reported in mainland China, with 15 840 (89%) being imported cases, mainly from Africa and south-east Asia. Almost all counties of China (2855/2858) had achieved their elimination goals by 2015, and locally transmitted cases dropped from 1469 cases in 2011 to 43 cases in 2015, mainly occurring in the regions bordering Myanmar whereThe locally transmitted malaria burden in China has decreased. The key challenge is to address the remaining local transmission, as well as to reduce imported cases from Africa and south-east Asia. Continued efforts and appropriate levels of investment are needed in the 2016-2020 period to achieve elimination.Déterminer l'évolution et la charge du paludisme en Chine ainsi que les coûts des interventions visant son élimination, pour la période de 2011 à 2015.Nous avons analysé les caractéristiques spatio-temporelles et démographiques des cas de transmission locale et d'importation du paludisme, en utilisant des données de surveillance désagrégées sur le paludisme couvrant les principaux vecteurs en Chine sur la période de 2011 à 2015. Les coûts totaux et moyens des efforts d'élimination du paludisme ont été calculés pour chaque source de financement, chaque type d'intervention et en fonction de la population exposée.Un total de 17 745 cas de paludisme, dont 123 mortels (0,7%), a été recensé en Chine continentale, avec 15 840 cas importés (89%), essentiellement depuis l'Afrique et l'Asie du Sud-Est. Pratiquement tous les comtés de Chine (2855/2858) ont atteint leurs objectifs vers l’élimination du paludisme en 2015, et les cas de transmission locale ont chuté de 1469 cas en 2011 à 43 cas en 2015, survenus principalement dans les régions bordant le Myanmar, où les espècesLa charge des cas de transmission locale du paludisme en Chine a diminué. Le principal défi consiste désormais à lutter contre la transmission locale résiduelle et à réduire les cas importés depuis l'Afrique et l'Asie du Sud-Est. Des efforts continus et des niveaux d'investissement appropriés sont nécessaires sur la période 2016-2020 pour atteindre l'objectif d'élimination du paludisme.Determinar las tendencias y la carga de paludismo en China y los costes de las intervenciones entre 2011 y 2015.Se analizaron las características espacio-temporales y demográficas de los casos de paludismo importado y transmitido localmente utilizando datos de seguimiento desglosados sobre el paludismo entre 2011 y 2015, y se cubrió la gama de vectores del paludismo dominantes en China. Se calcularon los costes totales y medios para la eliminación del paludismo teniendo en cuenta las fuentes de financiación, las intervenciones y la población en riesgo.En China continental se registró un total de 17 745 casos de paludismo, incluyendo 123 muertes (0,7%), de los cuales 15 840 (89%) fueron casos importados, principalmente de África y el sudeste asiático. Casi todos los condados de China (2 855/2 858) habían logrado sus objetivos de eliminación para 2015, y los casos transmitidos localmente descendieron de 1 469 casos en 2011 a 43 casos en 2015, principalmente en las regiones fronterizas con Myanmar, dondeLa carga de paludismo transmitido localmente en China ha disminuido. El reto principal es poner remedio a los casos transmitidos localmente que quedan, además de reducir los casos de importación de la infección desde África y el sudeste asiático. Durante el periodo 2016-2020, se necesitan esfuerzos continuos y niveles de inversión adecuados para lograr su eliminación.الغرض الوقوف على الاتجاهات السائدة وأعباء الملاريا في الصين وتكاليف التدخلات للفترة ما بين عامي 2011 و2015. الطريقة حللنا السمات المكانية والزمانية والديمغرافية لحالات الملاريا المنقولة محليًا والواردة باستخدام بيانات مراقبة مفصلة عن الملاريا في الفترة ما بين عامي 2011 و2015، والتي تغطي مجموعة ناقلات الملاريا السائدة في الصين. وقد تم حساب التكاليف الإجمالية والمتوسطة للتخلص من الملاريا على أساس مصادر التمويل والتدخلات والقطاعات السكانية المعرضة للخطر. النتائج وقد تم الإبلاغ عن وجود 17,745 حالة من حالات الملاريا، بما في ذلك 123 حالة وفاة (0.7‏%)، في البر الرئيسي للصين، مع وجود 15,840 حالة واردة (89‏%)، معظمها من أفريقيا وجنوب شرق آسيا. حققت جميع مقاطعات الصين تقريبًا (2855/2858) أهداف القضاء عليها بحلول عام 2015، وانخفضت الحالات المنقولة محليًا من 1469 حالة في عام 2011 إلى 43 حالة في عام 2015، والتي ظهرت أساسًا في المناطق المتاخمة لميانمار حيث تكون كلاً من الأنوفيلة الصغيرة والأنوفيلة الفظيعة كأنواع مسيطرة ناقلة للأمراض. وتم إنفاق ما يصل إلى 134.6 مليون دولار أمريكي في إطار الجهود المبذولة للقضاء على الملاريا خلال الفترة ما بين عامي 2011 و2015، حيث تم الحصول على 57.2 مليون دولار أمريكي (43‏%) من الصندوق العالمي لمحاربة الإيدز والسل والملاريا، و77.3 مليون دولار أمريكي (‏57%) من الحكومة المركزية الصينية. وبلغ متوسط الاستثمار السنوي (27 مليون دولار أمريكي) للشخص المعرض للخطر (574 مليون شخص) 0.05 دولار أمريكي (الانحراف المعياري: 0.03). الاستنتاج انخفض عبء الملاريا المنقولة محليًا في الصين. ويتمثل التحدي الرئيسي في معالجة النقل المحلي المتبقي، بالإضافة إلى الحد من الحالات الواردة من أفريقيا وجنوب شرق آسيا. ويلزم بذل جهود متواصلة ومستويات مناسبة من الاستثمار في الفترة ما بين عامي 2016 و2020 لتحقيق القضاء الكامل عليها.旨在明确 2011-2015 年间中国的疟疾流行趋势和压力及其干预措施成本。.我们使用 2011 至 2015 年间的分散型疟疾监测数据(涵盖中国的显性疟疾媒介的范围)分析了本地传播型及输入型疟疾病例的时空特征和人口特征。 消除疟疾的总成本及平均成本按资金来源、干预措施及危险人群数量进行计算。.中国大陆共报告了 17 745 件疟疾病例,其中包括 123 件 (0.7%) 死亡案例,15 840 件 (89%) 输入型病例。输入来源主要为非洲及东南亚。 中国几乎所有区县 (2855/2858) 已在 2015 年实现了其消灭疟疾的目标,本地传播型病例已由 2011 年的 1469 例下降至 2015 年的 43 例,主要发病区位于缅甸边境地带,该地区主要的媒介种类是中国的本地传播型疟疾疫情已经减轻。 应对剩余的本地传播以及减少来自非洲及东南亚地区的输入型病例是主要挑战。 2016-2020 年期间,中国仍需继续努力并进行适当投资以实现消除疟疾的目标。.Выяснить тенденции и нагрузку в отношении малярии в Китае, а также определить расходы на проведение необходимых мероприятий в период 2011–2015 гг.Мы провели анализ пространственно-временных и демографических особенностей случаев местнотрансмиссивной и завезенной малярии с использованием дезагрегированных данных эпиднадзора за малярией в период с 2011 по 2015 год, охватывающих диапазон доминирующих векторов малярии в Китае. Общие и средние затраты на ликвидацию малярии рассчитывались с учетом источников финансирования, необходимых мероприятий и групп населения, подверженных риску.Всего в континентальном Китае было зарегистрировано 17 745 случаев малярии, в том числе 123 случая со смертельным исходом (0,7%), из которых 15 840 случаев (89%) были завезены, главным образом из Африки и Юго-Восточной Азии. Почти все уезды Китая (2855 из 2858) достигли своих целей по ликвидации заболевания к 2015 году, а число местнотрансмиссивных случаев сократилось с 1469 случаев в 2011 году до 43 случаев в 2015 году, главным образом в регионах, граничащих с Мьянмой, гдеМестнотрансмиссивное бремя малярии в Китае снизилось. Основная задача состоит в том, чтобы решить сохраняющуюся проблему местной передачи инфекции, а также сократить случаи завоза инфекции из Африки и Юго-Восточной Азии. Для завершения ликвидации в 2016–2020 гг. необходимы дальнейшие усилия и соответствующие уровни инвестиций.

Terminally sialylated N-glycoproteins are of great interest in therapeutic applications. Due to the inability of prokaryotes to carry out this post-translational modification, they are currently predominantly produced in eukaryotic host cells. In this study, we report a synthetic pathway to produce a terminally sialylated N-glycoprotein in the periplasm of Escherichia coli, mimicking the sialylated moiety (Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-) of human glycans. A sialylated pentasaccharide, Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-β-1,3-Gal-β-1,3-GlcNAc-, was synthesized through the activity of co-expressed glycosyltransferases LsgCDEF from Haemophilus influenzae, Campylobacter jejuni NeuBCA enzymes, and Photobacterium leiognathi α-2,6-sialyltransferase in an engineered E. coli strain which produces CMP-Neu5Ac. C. jejuni oligosaccharyltransferase PglB was used to transfer the terminally sialylated glycan onto a glyco-recognition sequence in the tenth type III cell adhesion module of human fibronectin. Sialylation of the target protein was confirmed by lectin blotting and mass spectrometry. This proof-of-concept study demonstrates the successful production of terminally sialylated, homogeneous N-glycoproteins with α-2,6-linkages in the periplasm of E. coli and will facilitate the construction of E. coli strains capable of producing terminally sialylated N-glycoproteins in high yield.

Holothuria leucospilota (Echinodermata: Holothuroidea) is a widespread tropical sea cucumber with strong value for the ecological restoration of coral reefs. Therefore, some studies regarding the artificial breeding and cultivation of H. leucospilota have been undertaken recently. However, the biological functions of the digestive system of this species have not been elucidated. In this study, a cDNA coding for α-amylase, an indicator of digestive maturity in animals, was identified from H. leucospilota and designated Hl-Amy. The full-length cDNA of the Hl-Amy gene, which is 1734 bp in length with an open reading frame (ORF) of 1578 bp, encodes a 525 amino acid (a.a.) protein with a deduced molecular weight of 59.34 kDa. According to the CaZy database annotation, Hl-Amy belongs to the class of GH-H with the official nomenclature of α-amylase (EC 3.2.1.1) or 4-α-D-glucan glucanohydrolase. The Hl-Amy protein contains a signal peptide at the N-terminal followed by a functional amylase domain, which includes the catalytic activity site. The mRNA expression of Hl-Amy was abundantly exhibited in the intestine, followed by the transverse vessel with a low level, but was hardly detected in other selected tissues. During embryonic and larval development, Hl-Amy was constitutively expressed in all stages, and the highest expression level was observed in the blastula. By in situ hybridization (ISH), positive Hl-Amy signals were observed in different parts of the three different intestinal segments (foregut, midgut and hindgut). The Hl-Amy recombinant protein was generated in an E. coli system with codon optimization, which is necessary for Hl-Amy successfully expressed in this heterogenous system. The Hl-Amy recombinant protein was purified by immobilized metal ion affinity chromatography (IMAC), and its activity of starch hydrolysis was further detected. The optimal temperatures and pH for Hl-Amy recombinant protein were 55°C and 6.0, respectively, with an activity of 62.2 U/mg. In summary, this current study has filled a knowledge gap on the biological function and expression profiles of an essential digestive enzyme in sea cucumber, which may encourage future investigation toward rationalized diets for H. leucospilota in artificial cultivation, and optimized heterogenous prokaryotic systems for producing recombinant enzymes of marine origins.

A fluorescence immunoassay has been widely applied in different fields due to its high sensitivity, simple operations, and high accuracy. Quantum dots (QDs) are often selected as labels in a fluorescence immunoassay due to their high fluorescence, better stability, and biocompatibility. In this study, novel doped CdTe : Zn/ZnS QDs with stability and a high photoluminescence quantum yield (40.78%) were prepared by the water synthesis method and used as labels to conjugate with goat anti-rabbit IgG to establish a fluorescence immunoassay (FLISA) for bacteria compared to the traditional enzyme-linked immunosorbent assay (ELISA) based on the reaction between an antibody and an antigen. A good linear relationship between the fluorescence intensity and concentrations of

Escherichia coli has been considered as a promising host for the production of N-glycosylated therapeutic proteins and glycoconjugate vaccines. In this study, we developed a simple and efficient strategy for improving the production of N-glycosylated recombinant proteins by combining auto-induction with the use of a leaky E. coli strain. A leaky E. coli strain, designated as CLM37-Δlpp, was engineered by deleting the Braun’s lipoprotein (lpp) gene of E. coli strain CLM37. Three distinct acceptor model N-glycosylated proteins, glyco-tagged human tenth fibronectin type III domain (FN3-Gly), enhanced green fluorescent protein (eGFP-Gly), and scFv of vascular endothelial growth factor receptor 3 (scFv-VEGFR3-Gly) were then expressed in CLM37-Δlpp, which carried an N-glycosylation machinery from Campylobacter jejuni for the investigation of glycoprotein production. As much as 75%, 65%, and 60% of the glycosylated FN3-Gly, eGFP-Gly, and scFv-VEGFR3-Gly, respectively, were found in the culture medium. The yields of glycosylated FN3-Gly, eGFP-Gly, and scFv-VEGFR3-Gly were 106 ± 7.4 mg/L, 65 ± 2.5 mg/L, and 62 ± 4.3 mg/L, respectively, which were more than three folds the corresponding yields obtained when these proteins were expressed in CLM37, the unmodified strain. The results suggested that this simplified approach could improve the production of N-glycosylated proteins with E. coli to facilitate large-scale production.

Background In addition to non‐coding RNAs (lncRNAs) and microRNAs (miRNAs), circular RNAs (circRNAs) are endogenous RNAs with various functions, which have recently become a research hotspot. CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. They are more stable than linear RNAs. Methods Data were collected through PubMed. The following search terms were used: “circular RNA,” “circRNA,” “cancer,” “mechanism,” “biogenesis,” “biomarker,” “diagnosis.” Only articles published in English were included. Results Most circRNAs express tissue/developmental stage specificity. Moreover, circRNAs are involved in the regulation of a variety of biological activities. In this review, we discuss the formation, classification, and biological functions of circRNAs, especially their molecular diagnostic values in common cancers, including gastric cancer (hsa_circ_002059, circ_LARP4, hsa_circ_0000190, hsa_circ_0000096, circ‐SFMBT2, and circ_PVT1), hepatocellular carcinoma (circ_104075, circRNA_100338, circ_MTO1, and circZKSCAN1), colorectal cancer (hsa_circ_0136666 and hsa_circ_0000523), lung cancer (hsa_circ_0006427, circ_100876, and circ_ABCB10), breast cancer (hsa_circ_0089105, circAGFG1, and circEPSTI1), bladder cancer (circFNDC3B and circTFRC), and esophageal squamous cell carcinoma (circ_100876 and circ‐DLG1). Conclusion CircRNAs not only play important roles in tumorigenesis, but also may become new diagnostic biomarkers.

To improve the production yield of N-glycosylated anti-VEGFR2 (vascular endothelial growth factor receptor 2) monobody (FN3VEGFR2-Gly) in lpp knockout Escherichia coli cells harboring Campylobacter jejuni N-glycosylation pathway. The leaky CLM37-Δlpp strain efficiently secreted FN3VEGFR2-Gly into culture medium. The extracellular levels of glycosylated FN3VEGFR2-Gly in CLM37-Δlpp culture medium were approximately 11 and 15 times higher compared to those in CLM37 cells via IPTG and auto-induction, respectively. In addition, the highest level of total glycosylated FN3VEGFR2-Gly (70 ± 3.4 mg/L) was found in culture medium via auto-induction. Furthermore, glycosylated FN3VEGFR2-Gly was more stable than unglycosylated FN3VEGFR2-Gly in this expression system, but their bioactivities were relatively similar. Lpp knockout leaky E. coli strain combined with auto-induction method can enhance the extracellular production of homogenous N-glycosylated FN3VEGFR2-Gly, and facilitate the downstream protein purification. The findings of this study may provide practical implications for the large-scale production and cost-effective harvesting of N-glycosylation proteins.

Escherichia coli has been considered as a promising host for the production of N-glycosylated therapeutic proteins and glycoconjugate vaccines. In this study, we developed a simple and efficient strategy for improving the production of N-glycosylated recombinant proteins by combining auto-induction with the use of a leaky E. coli strain. A leaky E. coli strain, designated as CLM37-Δlpp, was engineered by deleting the Braun’s lipoprotein (lpp) gene of E. coli strain CLM37. Three distinct acceptor model N-glycosylated proteins, glyco-tagged human tenth fibronectin type III domain (FN3-Gly), enhanced green fluorescent protein (eGFP-Gly), and scFv of vascular endothelial growth factor receptor 3 (scFv-(VEGFR3)-Gly) were then expressed in CLM37-Δlpp, which carried an N-glycosylation machinery from Campylobacter jejuni for the investigation of glycoprotein production. As much as 75%, 65%, and 60% of the glycosylated FN3-Gly, eGFP-Gly, and scFv-(VEGFR3)-Gly, respectively, were found in the culture medium. The yields of glycosylated FN3-Gly, eGFP-Gly, and scFv-(VEGFR3)-Gly were 106 ± 7.4 mg/L, 65 ± 2.5 mg/L, and 62 ± 4.3 mg/L, respectively, which were more than three folds the corresponding yields obtained when these proteins were expressed in CLM37, the unmodified strain. The results suggested that this simplified approach could improve the production of N-glycosylated proteins with E. coli to facilitate large-scale production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-019-1830-5) contains supplementary material, which is available to authorized users.

In the crystal of the title compound, C10H13N2O3, inversion dimers linked by pairs of N—H...O hydrogen bonds generate R 2 2(6) loops. The dimers are linked by weak C—H...O and C—H...π interactions, resulting in a three-dimensional network. A short NO2...NO2 contact [3.107 (2) Å] is also seen.

Alternative splicing is an essential molecular mechanism that increase the protein diversity of a species to regulate important biological processes. As a transcription factor, Interleukin-2 enhancer binding factor 2 (ILF2) regulates the functions of interleukin-2 (IL-2) at the levels of transcription, splicing and translation, and plays other critical roles in the immune system. ILF2 is well-documented in vertebrates, while little is currently known in crustacean species such as the Pacific white shrimp (Litopenaeus vannamei). In the present study, five cDNA for spliced isoforms of Lv-ILF2 were identified, in which four of them are the full-length long isoforms (Lv-ILF2-L1, Lv-ILF2-L2, Lv-ILF2-L3 and Lv-ILF2-L4) and one of them is a truncated short isoform (Lv-ILF2-S). The whole sequence of ILF2 gene from L. vannamei was obtained, which is 11,680 bp in length with 9 exons separated by 8 introns. All five isoforms contain a domain associated with zinc fingers (DZF). Two alternative splicing types (alternative 5' splice site and alternative 3' splice site) were identified in the five isoforms. The Lv-ILF2 mRNA showed a broad distribution in all detected tissues, and the Lv-ILF2-L transcript levels were higher than those of Lv-ILF2-S in corresponding tissues. The mRNA levels of Lv-ILF2-S in the hepatopancreas, heart, muscle and stomach, but not in the eyestalk, were significantly increased after challenges with Vibrio harveyi or lipopolysaccharide (LPS), while no significant changes were observed for the transcript levels of Lv-ILF2-L in these tissues under the same immune stimulants. On the contrary, the transcript levels of neither Lv-ILF2-S nor Lv-ILF2-L were affected by challenges of polyinosinic: polycytidylic acid [Poly (I:C)]. In addition, after knockdown of the Lv-ILF2 mRNA level by siRNA, the mortality of shrimp and the hepatopancreatic bacterial numbers were significantly increased under V. harveyi challenge, indicating that Lv-ILF2 might participate in the immune defenses against V. harveyi invasion. Collectively, our study here supplied the first evidence for a novel splicing mechanism of ILF2 transcripts, and provided a functional link between the Lv-ILF2 isoforms and the capacity against pathogenic Vibrio in penaeid shrimp.

Egg spoilage is a microecological phenomenon, involving several specific spoilage microorganisms, that is affected by numerous factors. The specific biological characteristics of egg spoilage microorganisms are particularly significant for their survival in eggs. This research focusses on the specific biological characteristics of 24 spoilage bacteria isolated from eggs. Their protease activities, alkalinity tolerance, egg white and lysozyme tolerance, and survival rates in egg whites were analysed. The results showed that the strains of Bacillus spp. had the strongest protease activity, the strains of Staphylococcus spp. had the strongest alkaline pH tolerance, and most of the spoilage bacteria could tolerate an egg white or lysozyme environment. Notably, the survival rate test of egg whites showed that only the strains of Dermacoccus spp. could survive and grow in egg whites. This study of the specific biological characteristics of spoilage microorganisms in eggs aims to extend eggs’ shelf life and provide theoretical guidance for controlling spoilage microorganisms during storage.

Na+/H+ exchangers are the most common membrane proteins involved in the regulation of intracellular pH that concurrently transport Na+ into the cells and H+ out of the cells. In this study, the full-length cDNA of the Na+/H+ exchanger (NHE) from the Pacific white shrimp (Litopenaeus vannamei) was cloned. The LvNHE cDNA is 3167 bp long, contains a 5'-untranslated region (UTR) of 74 bp and a 3'-UTR of 456 bp and an open reading frame (ORF) of 2637 bp, coding for a protein of 878 amino acids with 11 putative transmembrane domains and a long cytoplasmic tail. LvNHE shows high sequence homology with mud crab NHE at the amino acid level. LvNHE mRNA was detected in the hepatopancreas, gill, eyestalk, skin, heart, intestine, muscle, brain and stomach, with the highest abundance in the intestine. In the shrimp intestinal fragment cultures exposed to gradually declining pH medium (from pH 8.0 to pH 6.4), the LvNHE mRNA expression was significantly stimulated, with the highest response when incubated in pH 7.0 medium for 6 h. To investigate the functional roles of LvNHE in pH regulation at the physiological and cellular levels, the LvNHE mRNA expression was silenced by siRNA knockdown. Upon low-pH challenge, the hemolymph pH was significantly reduced in the LvNHE mRNA knockdown shrimp. In addition, knockdown of LvNHE mRNA reduced the recovery capacity of intracellular pH in intestinal fragment cultures after acidification. Altogether, this study demonstrates the role of NHE in shrimp response to low pH stress and provides new insights into the acid/base homeostasis mechanisms of crustaceans.

Precise diagnosis is a key measure for malaria control and elimination, and malaria microscopy is still the gold standard method recommended by the World Health Organization (WHO) for malaria diagnosis. Analysis of the competency in malaria microscopy in China will benefit to identify the challenges in this skill and provide some suggestions for improvement in order to reach the requirement of WHO procedures for certification of malaria elimination, and finally contribute to malaria elimination by 2020 in China. According to a series of external assessment activities about malaria microscopy, malaria microscopists from both the national and provincial level but not the levels below provincial level performed quite well in Plasmodium spp identification, but their competency in differentiation of P. ovale and P. vivax and parasite counting by microscopy were not good enough at all levels. Therefore, it is necessary to strengthen the competency in species identification and parasite counting especially at the lower levels in the first line through training and practice as well as regular quality assurance with enough policy support.

Background Hypercholesterolemia is an important key contributory factor for ischemic heart disease and is associated with age, high blood pressure, a family history of hypercholesterolemia, and diabetes. Chinese herbal medicines have been used for a long time as lipid-lowering agents. Objectives To assess the effects of Chinese herbal medicines on hypercholesterolemia. Search methods We searched the following databases: The Cochrane Library (issue 8, 2010), MEDLINE (until July 2010), EMBASE (until July 2010 ), Chinese BioMedical Database (until July 2010), Traditional Chinese Medical Literature Analysis and Retrieval System (until July 2010), China National Knowledge Infrastructure (until July 2010), Chinese VIP Information (until July 2010), Chinese Academic Conference Papers Database and Chinese Dissertation Database (until July 2010), and Allied and Complementary Medicine Database (until July 2010). Selection criteria We considered randomized controlled clinical trials in hypercholesterolemic participants comparing Chinese herbal medicines with placebo, no treatment, and pharmacological or non-pharmacological interventions. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias. We resolved any disagreements with this assessment through discussion and a decision was achieved based by consensus. We assessed trials for the risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective outcome reporting and other sources of bias. Main results We included 22 randomized trials (2130 participants). The mean treatment duration was 2.3 ± 1.3 months (ranging from one to six months). Twenty trials were conducted in China and 18 trials were published in Chinese. Overall, the risk of bias of included trials was high or unclear. Five different herbal medicines were evaluated in the included trials, which compared herbs with conventional medicine in six comparisons (20 trials), or placebo (two trials). There were no outcome data in any of the trials on cardiovascular events and death from any cause. One trial each reported well-being (no significant differences) and economic costs. No serious adverse events were observed. Xuezhikang was the most commonly used herbal formula investigated. A significant effect on total cholesterol (two trial, 254 participants) was shown in favor of Xuezhikang when compared with inositol nicotinate (mean difference (MD) -0.90 mmol/L, 95% confidence interval (CI) -1.13 to -0.68) . Authors' conclusions Some herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.

Background The number of pulmonary tuberculosis (PTB) cases in China ranks third in the world. A continuous increase in cases has recently been recorded in Zhaotong prefecture-level city, which is located in the northeastern part of Yunnan province. This study explored the space-time dynamics of PTB cases in Zhaotong to provide useful information that will help guide policymakers to formulate effective regional prevention and control strategies. Methods The data on PTB cases were extracted from the nationwide tuberculosis online registration system. Time series and spatial cluster analyses were applied to detect PTB temporal trends and spatial patterns at the town level between 2011 and 2015 in Zhaotong. Three indicators of PTB treatment registration history were used: initial treatment registration rate, re-treatment registration rate, and total PTB registration rate. Results Seasonal trends were detected with an apparent symptom onset peak during the winter season and a registration peak during the spring season. A most likely cluster and six secondary clusters were identified for the total PTB registration rate, one most likely cluster and five secondary clusters for the initial treatment registration rate, and one most likely cluster for the re-treatment registration rate. The most likely cluster of the three indicators had a similar spatial distribution and size in Zhenxiong County, which is characterised by a poor socio-economic level and the largest population in Yunnan. Conclusion This study identified temporal and spatial distribution of PTB in a high PTB burden area using existing health data. The results of the study provide useful information on the prevailing epidemiological situation of PTB in Zhaotong and could be used to develop strategies for more effective PTB control at the town level. The cluster that overlapped the three PTB indicators falls within the geographic areas where PTB control efforts should be prioritised.