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Thromboembolism caused by the use of extracorporeal membrane oxygenation (ECMO) remains common among patients with existing heart diseases and contributes to significant morbidity and mortality during the COVID-19 pandemic. Various surface modification strategies have been proposed, showing that the methacrylated alginate (MA-SA) hydrogel layer is transparent, which aids the observation of the thromboembolism from the inner wall of the tubing. In the combined dynamic and static blood of ECMO tubing inner surface in vitro experiments, it was also demonstrated that the adhesion of blood clots to the surface of vessels was remarkably reduced, and the MA-SA-based hydrogel coating could significantly prolong the activated partial thrombin time and block the endogenous coagulation. The favorable properties of natural polysaccharides of hydrogel coatings make them the best surface material choices to be applied for blood-contacting medical devices and significantly improve anticoagulant performance.

ABSTRACT: Bacterial antimicrobial resistance (AMR) continues to develop, with the horizontal transfer of antibiotic resistance genes (ARGs) through plasmids playing a major role. Recently, the antimicrobial resistance of R. anatipestifer has become increasingly severe, jeopardizing the development of the poultry industry. In this study, we used PromethION to determine the whole genome sequence of R. anatipestifer RCAD0416, a multidrug-resistant isolate from China. We detected a plasmid in the isolate. We named the plasmid pRCAD0416RA-1; the plasmid was 37356 bp in size with 36 putative open reading frames and included the blaOXA-347, floR, tet(X), ermF, ereD, and AadS resistance genes. Most resistance genes might be obtained from R. anatipestifer HXb2. Mobile elements and floR might be transmitted by plasmid pB18–2 from Acinetobacter indicus, and the ICEPg6Chn1 mobile elements can be transmitted from Proteus genomosp. The plasmid pRCAD0416RA-1 was transferred to Escherichia coli K-12 × 7232 via electroporation. Subsequent antimicrobial sensitivity tests (AST) showed a noticeable levels of antimicrobial resistance to β-lactams (4–8 fold), tigecycline (8 fold), and florfenicol (8 fold). These types of antibiotics are in common clinical use. The purpose of this article is to elucidate the basic characteristics of pRCAD0416RA-1 and the level of resistance mediated by blaOXA-347, floR, and tet(X).

ABSTRACT Tembusu virus (TMUV), an avian mosquito-borne flavivirus, was first identified from Culex tritaeniorhynchus in 1955. To validate the effects of the 3′-untranslated region (3′UTR) in viral host-specific adaptation, we generated a set of chimeric viruses using CQW1 (duck strain) and MM 1775 (mosquito strain) as backbones with heterogeneous 3′UTRs. Compared with rMM 1775, rMM-CQ3′UTR (recombinant MM 1775 virus carrying the 3′UTR of CQW1) exhibited enhanced proliferation in vitro, with peak titers increasing by 5-fold in duck embryonic fibroblast (DEF) cells or 12-fold in baby hamster kidney (BHK-21) cells; however, the neurovirulence of rMM-CQ3′UTR was attenuated in 14-day-old Kunming mice via intracranial injection, with slower weight loss, lower mortality, and reduced viral loads. In contrast, rCQ-MM3′UTR showed similar growth kinetics in vitro and neurovirulence in mice compared with those of rCQW1. Then, the Stem-loop I (SLI) structure, which showed the highest variation within the 3′UTR between CQW1 and MM 1775, was further chosen for making chimeric viruses. The peak titers of rMM-CQ3′UTRSLI displayed a 15- or 4-fold increase in vitro, and the neurovirulence in mice was attenuated, compared with that of rMM 1775; rCQ-MM3′UTRSLI displayed comparable multiplication ability in vitro but was significantly attenuated in mice, in contrast with rCQW1. In conclusion, we demonstrated that the TMUV SLI structure of the 3′UTR was responsible for viral host-specific adaptation of the mosquito-derived strain in DEF and BHK-21 cells and regulated viral pathogenicity in 14-day-old mice, providing a new understanding of the functions of TMUV 3′UTR in viral host switching and the pathogenicity changes in mice. IMPORTANCE Mosquito-borne flaviviruses (MBFVs) constitute a large number of mosquito-transmitted viruses. The 3′-untranslated region (3′UTR) of MBFV has been suggested to be relevant to viral host-specific adaptation. However, the evolutionary strategies for host-specific fitness among MBFV are different, and the virulence-related structures within the 3′UTR are largely unknown. Here, using Tembusu virus (TMUV), an avian MBFV as models, we observed that the duck-derived SLI of the 3′UTR significantly enhanced the proliferation ability of mosquito-derived TMUV in baby hamster kidney (BHK-21) and duck embryonic fibroblast (DEF) cells, suggesting that the SLI structure was crucial for viral host-specific adaptation of mosquito-derived TMUVs in mammalian and avian cells. In addition, all SLI mutant viruses exhibited reduced viral pathogenicity in mice, indicating that SLI structure was a key factor for the pathogenicity in mice. This study provides a new insight into the functions of the MBFV 3′UTR in viral host switching and pathogenicity changes in mice.

Duck plague virus (DPV) belongs to the alphaherpesvirinae and causes high morbidity and mortality in waterfowl. UL47 is a large abundant structural protein in DPV, which means that UL47 protein plays an important role in virus replication. US3 protein, as a viral protein kinase in alphaherpesviruses, has been reported to be critical for DPV virion assembly. In this study, we over-expressed UL47 and US3 proteins and found that DPV UL47 protein was a phosphorylated substrate of US3 protein, which interacted and co-localized with US3 protein in the cytoplasm. US3-regulated phosphorylation of UL47 was important for the cytoplasmic localization of UL47 because non-phosphorylated UL47 was localized in the nucleus. The six sites of UL47 at Thr29, Ser30, Ser42, Thr47, Ser161, and Thr775 were identified as the phosphorylation targets of US3 protein. In vivo, UL47 phosphorylation was also detected but not in ΔUS3-infected cells. US3 protein promoted the cytoplasmic localization of UL47 at the late stage of infection, and the lack of US3 protein caused a delay in UL47 translocation to the cytoplasm. These results enhance our understanding of the functions of US3 during DPV infection and provide some references for DPV assembly.

Salmonella enterica is a widespread foodborne pathogen with concerning antimicrobial resistance (AMR). Waterfowl are a major source of Salmonella transmission, but there are few systematic studies on Salmonella prevalence in waterfowl species. In this study, 126 Salmonella isolates (65 collected in 2018–2020 and 61 collected in 2002–2005) were obtained from waterfowl samples in Sichuan, China. Their serotypes, pulsed-field gel electrophoresis (PFGE) types, and phenotypic and genotypic AMR profiles were systematically examined. The isolates were distributed in 7 serotypes, including serovars Enteritidis (46.0%), Potsdam (27.8%), Montevideo (7.9%), Cerro (6.3%), Typhimurium (4.8%), Kottbus (4.0%) and Apeyeme (3.2%). Their PFGE characteristics were diverse; all isolates were distributed in four groups (cutoff value: 60.0%) and 20 clusters (cutoff value: 80.0%). Moreover, all isolates were multidrug resistant, and high rates of AMR to lincomycin (100.0%), rifampicin (100.0%), sulfadiazine (93.7%), erythromycin (89.7%), ciprofloxacin (81.0%), and gentamicin (75.4%) were observed. Finally, 49 isolates were subjected to whole-genome sequencing, and a wide variety of AMR genes were found, including multiple efflux pump genes and specific resistance genes. Interestingly, the tet(A)/tet(B) and catII resistance genes were detected in only isolates obtained in the first collection period, while the gyrA (S83F, D87N and D87G) and gyrB (E466D) mutations were detected at higher frequencies in the isolates obtained in the second collection period, supporting the findings that isolates from different periods exhibited different patterns of resistance to tetracycline, chloramphenicol and nalidixic acid. In addition, various incompatible plasmid replicon fragments were detected, including Col440I, Col440II, IncFIB, IncFII, IncX1, IncX9, IncI1-I and IncI2, which may contribute to the horizontal transmission of AMR genes and provide competitive advantages. In summary, we demonstrated that the Salmonella isolates prevalent in Sichuan waterfowl farms exhibited diverse serotypes, multiple AMR phenotypes and genotypes, and AMR changes over time, indicating their potential risks to public health.

ABSTRACT: Flavivirus RNA cap-methylation plays an important role in viral infection, proliferation, and escape from innate immunity. The methyltransferase (MTase) of the flavivirus NS5 protein catalyzes viral RNA methylation. The E218 amino acid of the NS5 protein MTase domain is one of the active sites of flavivirus methyltransferase. In flaviviruses, the E218A mutation abolished 2’-O methylation activity and significantly reduced N-7 methylation activity. Tembusu virus (TMUV, genus Flavivirus) was a pathogen that caused neurological symptoms in ducklings and decreased egg production in laying ducks. In this study, we focused on a comprehensive understanding of the effects of the E218A mutation on TMUV characteristics and the host immune response. E218A mutation reduced TMUV replication and proliferation, but did not affect viral adsorption and entry. Based on a TMUV replicon system, we found that the E218A mutation impaired viral translation. In addition, E218A mutant virus might be more readily recognized by RIG-I-like receptors to activate the corresponding antiviral immune signaling than WT virus. Together, our data suggest that the E218A mutation of TMUV MTase domain impairs viral replication and translation and may activates RIG-I-like receptor signaling, ultimately leading to a reduction in viral proliferation.

ABSTRACT: The nomenclature of duck viral hepatitis (DVH) was historically not a problem. However, 14 hepatotropic viruses among 10 different genera are associated with the same disease name, DVH. Therefore, the disease name increasingly lacks clarity and may no longer fit the scientific description of the disease. Because one disease should not be attributed to 10 genera of viruses, this almost certainly causes misunderstanding regarding the disease-virus relationship. Herein, we revisited the problem and proposed an update to DVH disease classification. This classification is based on the nomenclature of human viral hepatitis and the key principle of Koch's postulates (“one microbe and one disease”). In total, 10 types of disease names have been proposed. These names were literately matched with hepatitis-related viruses. We envision that this intuitive nomenclature system will facilitate scientific communication and consistent interpretation in this field, especially in the Asian veterinary community, where these diseases are most commonly reported.

With the large-scale use of antibiotics, antibiotic resistant bacteria (ARB) continue to rise, and antibiotic resistance genes (ARGs) are regarded as emerging environmental pollutants. The new tetracycline-class antibiotic, tigecycline is the last resort for treating multidrug-resistant (MDR) bacteria. Plasmid-mediated horizontal transfer enables the sharing of genetic information among different bacteria. The tigecycline resistance gene tet(X) threatens the efficacy of tigecycline, and the adjacent ISCR2 or IS26 are often detected upstream and downstream of the tet(X) gene, which may play a crucial driving role in the transmission of the tet(X) gene. Since the first discovery of the plasmid-mediated high-level tigecycline resistance gene tet(X4) in China in 2019, the tet(X) genes, especially tet(X4), have been reported within various reservoirs worldwide, such as ducks, geese, migratory birds, chickens, pigs, cattle, aquatic animals, agricultural field, meat, and humans. Further, our current researches also mentioned viruses as novel environmental reservoirs of antibiotic resistance, which will probably become a focus of studying the transmission of ARGs. Overall, this article mainly aims to discuss the current status of plasmid-mediated transmission of different tet(X) genes, in particular tet(X4), as environmental pollutants, which will risk to public health for the “One Health” concept.

Primary seminal vesicle tumors are extremely rare. Several rare pathological types of primary seminal vesicle tumors have been reported, such as adenocarcinoma, but there is no report on adenofibroma. We report the first case of adenofibroma arising from the seminal vesicle. A 50-year-old man, with no history or clinical evidence of any other tumors, accidentally found a pelvic mass during an ultrasound examination. As the mass grew, the patient developed mild constipation, without genitourinary or other symptoms. All laboratory examinations were normal. MRI of the pelvis revealed a mixed density, measuring 11.7×9.9×8.2cm, well circumscribed mass. The rectum, bladder, prostate and lymph nodes were normal. We successfully performed the open surgery and removed the mass. Histopathological results confirmed that the mass was a primary seminal vesicle adenofibroma. In literature, we found that for biphasic differentiated tumors, it is easy to reduce the accuracy of pathological diagnosis because of insufficient puncture. Therefore, preoperative puncture biopsy for seminal vesicle tumors should be investigated further.

BackgroundDiastolic wall shear stress (WSS), assessed by using vector flow mapping (VFM), is the result of the interaction between the blood flow and the ventricular wall. This study aimed to evaluate the trend of left ventricular (LV) WSS in normal subjects.Methods and resultsA total of 371 healthy volunteers were recruited and divided into four age groups (group I: 18–30 years; group II: 31–43 years; group III: 44–56 years; group IV: 57–70 years). LV WSS of different age groups was measured at each diastolic phase (P1: isovolumic diastolic period, P2: rapid filling period, P3: slow filling period, and P4:atrial contraction period) to evaluate the change trend of LV WSS. In each age group, LV WSS coincided with a trend of increasing-decreasing-increasing during P1–P4 (P < 0.05). Besides, among groups I, II, III, and IV, WSS of anterolateral, inferoseptal, and anteroseptal in P1 and WSS of inferolateral, inferoseptal, and anteroseptal in P4 all showed an increasing trend with age (P < 0.05). Regarding sex differences, women had greater diastolic WSS compared to men (P < 0.05).ConclusionLV WSS showed a regular variation and had specific age- and sex-related patterns in different diastolic phases.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by local invasion and recurrence. RNA sequencing (RNA-seq) allows the qualification of cellular RNA populations and provides information on the transcriptional state. However, few studies have comprehensively analyzed DFSP transcriptional data.Methods: Fourteen DFSP samples with paired non-neoplastic soft tissue from Chinese patients undergoing Mohs micrographic surgery were used for RNA-seq analysis. Differential expression analysis and enrichment analysis for RNA-seq data were performed to identify fusion genes, biomarkers, and microenvironment characteristics of DFSP.Results: This study systemically describes the transcriptomic characteristics of DFSP. First, we performed gene fusion analysis and identified a novel FBN1-CSAD fusion event in a DFSP patient with fibrosarcomatous transformation. Then, we identified TLK2 as a biomarker for DFSP based on functional enrichment analysis, and validated its accuracy for diagnosing DFSP by immunohistochemical staining and joint analysis with public data. Finally, microenvironment analysis described the infiltration characteristics of immune and stromal cells in DFSP.Conclusion: This study demonstrates that RNA-seq can serve as a promising strategy for exploring molecular mechanisms in DFSP. Our results provide new insights into accurate diagnosis and therapeutic targets of DFSP.

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that are implicated in RNA metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most hnRNPs were predominantly located in the nucleus, but some of them could redistribute to the cytoplasm during virus infection. HnRNPs consist of different domains and motifs that enable these proteins to recognize predetermined nucleotide sequences. In the virus-host interactions, hnRNPs specifically bind to viral RNA or proteins. And some of the viral protein-hnRNP interactions require the viral RNA or other host factors as the intermediate. Through various mechanisms, hnRNPs could regulate viral translation, viral genome replication, the switch of translation to replication and virion release. This review highlights the common features and the distinguish roles of hnRNPs in the life cycle of positive single-stranded RNA viruses.

Background: DNA methylation is an important form of epigenetic regulation and is closely related to atherosclerosis (AS). The purpose of this study was to identify DNA methylation–related biomarkers and explore the immune-infiltrate characteristics of AS based on methylation data.Methods: DNA methylation data of 15 atherosclerotic and paired healthy tissues were obtained from Gene Expression Omnibus database. Differential methylation positions (DMPs) and differential methylation regions (DMRs) were screened by the ChAMP R package. The methylation levels of DMPs located on CpG islands of gene promoter regions were averaged. The limma R package was used to screen differentially methylated genes in the CpG islands of the promoter regions. The diagnostic values of the methylation levels were evaluated using the pROC R package. The EpiDISH algorithm was applied to quantify the infiltration levels of seven types of immune cells. Subsequently, three pairs of clinical specimens of coronary atherosclerosis with Stary’s pathological stage III were collected, and the methylation levels were detected by the methylation-specific PCR (MS-PCR) assay. Western blot was performed to detect the protein expression levels of monocyte markers.Results: A total of 110, 695 DMPs, and 918 DMRs were screened in the whole genome. Also, six genes with significant methylation differences in the CpG islands of the promoter regions were identified, including 49 DMPs. In total, three genes (GRIK2, HOXA2, and HOXA3) had delta beta greater than 0.2. The infiltration level of monocytes was significantly upregulated in AS tissues. MS-PCR assay confirmed the methylation status of the aforementioned three genes in AS samples. The Western blot results showed that the expression levels of the monocyte marker CD14 and M1-type macrophage marker CD86 were significantly increased in AS while M2-type macrophage marker protein CD206 was significantly decreased.Conclusion: This study identified potential DNA methylation–related biomarkers and revealed the role of monocytes in early AS.

A gas–solid-coupled sandwich combustion model was established for ammonium perchlorate (AP)/hydroxyl-terminated polybutadiene (HTPB) composite propellant. Numerical simulations were conducted to investigate the influence of the content of AP and the relative position of the coarse AP on the flame structure and the burning rate of the propellant. The results indicated that the overall AP mass fraction has a significant effect on the gas-phase flame temperature and burning rate, and there exists an optimal oxygen-to-fuel ratio that maximizes the burning rate. As the mass fraction of fine AP increased, the premixed flame above the binder matrix gradually took over the dominance of the diffusion flame, and the intensity of the diffusion flame near the interface of coarse AP and binder matrix also increased, resulting in a significant increase in the burning rate. As the mass fraction of fine AP increases from 0% to 70.0%, the average surface temperature increases from 937 K to 1026 K, and the burning rate rises from 0.9 cm/s to 2.7 cm/s. The location of the coarse AP causes the flame tilts to the side with less binder matrix, but it had little effect on the burn rate of the propellant.

Microplastics (MPs) have been given considerable attention due to their risk to aquatic organisms in marine environments. In this study, MPs’ abundance and their potential correlation with environmental factors were investigated from 26 sites in Daya Bay, South China Sea. The results showed that the abundance of MPs was 1.8–13.87 items/L in surface water and 190–823 items/kg (dry weight) in sediment. The most abundant shape of MPs in both water and sediment was fiber, the most abundant particle size was 0.5–1 mm and the most abundant color was transparent. In addition, the most common polymer type of MPs was polyethylene terephthalate (PET), followed by rayon (RY), polypropylene (PP), cellulose (CL) and polyethylene (PE). The abundance of MPs in sediment was significantly correlated with sediment organic N and C (p < 0.05), while that in surface water had no significant correlation with the environmental factors except dissolved oxygen (p > 0.05). A factor analysis showed that MPs in sediment might share similar sources with organic N and C, which were mainly from the autochthonous sedimentation of marine organisms, and MPs might sediment jointly with organic matter. In summary, this study reflects on MP pollution and the potential correlation with environmental factors, providing essential data for governmental agencies to formulate microplastic pollution control policies.

Abstract Background Autologous adipose tissue transfer may be performed for aesthetic needs following the resection of dermatofibrosarcoma protuberans (DFSP), the most common cutaneous soft tissue sarcoma, excluding Kaposi sarcoma. The regenerative effectiveness of cell-assisted lipotransfer is dependent on the presence of adipose tissue-derived stem cells (ADSCs). This is the first study to evaluate the potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of DFSP cells. Methods Primary DFSP cells were indirectly co-cultured with ADSCs in a conditioned medium or in a Transwell system. The impact was analyzed by assessing proliferation, migration, invasion, angiogenesis, and tumor-associated genes and proteins. Results of these assays were compared between co-culture and mono-culture conditions. Results Our experimental results showed that ADSCs were able to promote proliferation, migration, invasion, and angiogenesis of DFSP cells; this was accompanied by a significant increase in the expression levels of beta-type platelet-derived growth factor receptor, collagen type I alpha 1 chain, vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor. Conclusions The current report clearly demonstrates that ADSCs can enhance different malignant properties of DFSP cells in vitro, which should not be neglected when considering the clinical use of human ADSCs and its related derivatives in skin regenerative therapies.

The preparation of chiral monolayer-protected metal clusters is interesting for their potential applications in a variety of fields, including catalysis. Here, the authors synthesize chiral Ag14 nanoclusters in an all-achiral environment, and decipher the origin of chirality at the molecular level; the solvent choice is key to achieve homochiral crystallization.

Abstract Background Cassava is an important crop for food security and industry in the least-developed and developing countries. The completion of the cassava genome sequence and identification of large numbers of candidate genes by next-generation sequencing provide extensive resources for cassava molecular breeding and increase the need for rapid and efficient gene function analysis systems in cassava. Several plant virus-induced gene silencing (VIGS) systems have been developed as reverse genetic tools for rapid gene function analysis in cassava. However, these VIGS vectors could cause severe viral symptoms or inefficient gene silencing. Results In this study, we constructed agroinfection-compatible infectious cDNA clones of cassava common mosaic virus isolate CM (CsCMV-CM, genus Potexvirus, family Alphaflexiviridae) that causes systemic infection with mild symptoms in cassava. CsCMV-CM was then modified to a viral vector carrying the Nimble cloning frame, which facilitates the rapid and high-throughput cloning of silencing fragments into the viral genome. The CsCMV-based vector successfully silenced phytoene desaturase (PDS) and magnesium chelatase subunit I (ChlI) in different cassava varieties and Nicotiana benthamiana. The silencing of the ChlI gene could persist for more than two months. Conclusions This CsCMV-based VIGS system provides a new tool for rapid and efficient gene function studies in cassava.

Abstract Background The range of body sizes in Carnivora is unparalleled in any other mammalian order—the heaviest species is 130,000 times heavier than the lightest and the longest species is 50 times longer than the shortest. However, the molecular mechanisms underlying these huge differences in body size have not been explored. Results Herein, we performed a comparative genomics analysis of 20 carnivores to explore the evolutionary basis of the order’s great variations in body size. Phylogenetic generalized least squares (PGLS) revealed that 337 genes were significantly related to both head body length and body mass; these genes were defined as body size associated genes (BSAGs). Fourteen positively-related BSAGs were found to be associated with obesity, and three of these were under rapid evolution in the extremely large carnivores, suggesting that these obesity-related BSAGs might have driven the body size expansion in carnivores. Interestingly, 100 BSAGs were statistically significantly enriched in cancer control in carnivores, and 15 of which were found to be under rapid evolution in extremely large carnivores. These results suggested that large carnivores might have evolved an effective mechanism to resist cancer, which could be regarded as molecular evidence to support Peto’s paradox. For small carnivores, we identified 15 rapidly evolving genes and found six genes with fixed amino acid changes that were reported to reduce body size. Conclusions This study brings new insights into the molecular mechanisms that drove the diversifying evolution of body size in carnivores, and provides new target genes for exploring the mysteries of body size evolution in mammals.

Abstract Microbial flocculants are macromolecular substances produced by microorganisms. Due to its non-toxic, harmless, and biodegradable advantages, microbial flocculants have been widely used in various industrial fields, such as wastewater treatment, microalgae harvest, activated sludge dewatering, heavy metal ion adsorption, and nanoparticle synthesis, especially in the post-treatment process of fermentation with high safety requirement. However, compared with the traditional inorganic flocculants and organic polymeric flocculants, the high production cost is the main bottleneck that restricts the large-scale production and application of microbial flocculants. To reduce the production cost of microbial flocculant, a series of efforts have been carried out and some exciting research progresses have been achieved. This paper summarized the research advances in the last decade, including the screening of high-yield strains and the construction of genetically engineered strains, search of cheap alternative medium, the extraction and preservation methods, microbial flocculants production as an incidental product of other biological processes, combined use of traditional flocculant and microbial flocculant, and the production of microbial flocculant promoted by inducer. Moreover, this paper prospects the future research directions to further reduce the production cost of microbial flocculants, thereby promoting the industrial production and large-scale application of microbial flocculants.

Background: The deeper understanding of the complex hereditary basis of familial hypercholesterolemia (FH) has raised the rationale of genetic testing, which has been underutilized in clinical practice. Objectives: The present study aimed to explore the variant spectrum of FH in an expanding manner and compare its diagnostic performance. Methods: A total of 169 Chinese individuals (124 index cases and 45 relatives) with clinical definite/probable FH were consecutively enrolled. Next-generation sequencing was performed for genetic analysis of 9 genes associated with hypercholesterolemia (major genes: LDLR, APOB, and PCSK9; minor genes: LDLRAP1, LIPA, STAP1, APOE, ABCG5, and ABCG8) including the evaluations of small-scale variants and large-scale copy number variants (CNVs). Results: Among the 169 clinical FH patients included, 98 (58.0%) were men. A total of 85 (68.5%) index cases carried FH-associated variants. The proportion of FH caused by small-scale variants in LDLR, APOB, and PCSK9 genes was 62.1% and then increased by 6.5% when other genes and CNVs were further included. Furthermore, the variants in LDLR, APOB, and PCSK9 genes occupied 75% of all FH-associated variants. Of note, there were 8 non-LDLR CNVs detected in the present study. Conclusions: LDLR, APOB, and PCSK9 genes should be tested in the initial genetic screening, although variants in minor genes also could explain phenotypic FH, suggesting that an expanding genetic testing may be considered to further explain phenotypic FH.

Duck plague caused by duck plague virus (DPV) is a highly contagious disease that can cause serious morbidity and death in waterfowl such as ducks and geese, and bring huge economic losses to the duck industry. In this study, on the basis of the duck plague virus gC gene deletion strain CHv-ΔgC, based on the duck plague virus bacterial artificial chromosome (BAC) platform in our laboratory, the gE gene was knocked out using the traceless deletion technology to obtain gC/gE double gene deletion candidate vaccine strain CHv-ΔgC/gE. The double gene deletion strain (CHv-ΔgC/gE) constructed in this study has greatly weakened virulence, no pathogenicity to ducks, and stable genetic characteristics in vitro and in vivo. Ducks immunized with CHv-ΔgC/gE can produce neutralizing antibodies and ELISA antibody levels comparable to those of commercial duck plague attenuated vaccine immunization, and can resist 100 LD50 CHv challenge of ducks, with good immune protection effect. It has the potential to be further developed into duck plague gC/gE double gene deletion, marked attenuated vaccine.

BackgroundPatients with radioactive iodine refractory progressive (RAIR) differentiated thyroid cancer (DTC) often developed resistance after first-line therapy. Apatinib plus camrelizumab is a therapy with promising efficacy in patients with other malignant cancers. Herein, we presented a case of progressive RAIR DTC treated with apatinib plus camrelizumab.Case presentationWe reported a 43-year-old man diagnosed as DTC with metastases in the lungs, the 7th cervical vertebra, and malignant lymph nodes mainly in the mediastinum. While initially showing disease stabilization after giving the first-line multitargeted kinase inhibitor (MKI) therapy, the patient developed progressive disease and was enrolled into a combined therapy with both apatinib and camrelizumab on November 10, 2020. Upon the first 6 months, the combination therapy showed disease control in terms of both stable structural lesions and biochemical thyroglobulin (Tg) level. Six months later, a decrease over the targeted lesions was observed and a partial response (PR) according to RECIST 1.1 criteria was finally achieved upon 12 months’ assessment, followed by the decline in serum Tg level. The main adverse event was occasional diarrhea without treatment interruption.ConclusionWe reported a case with RAIR DTC that benefited from combination immunotherapy, apatinib plus camrelizumab, after resistance from donafenib. We observed a gradually getting better efficacy and a mild and long duration of this combination therapy and hoped to provide a therapeutic choice for these patients.

The viral envelope glycoprotein E (gE) is required for cell-to-cell transmission, anterograde and retrograde neurotransmission, and immune evasion of alphaherpesviruses. gE can also interact with other proteins of the virus and perform various functions in the virus life cycle. In addition, the gE gene is often the target gene for the construction of gene-deleted attenuated marker vaccines. In recent years, new progress has been made in the research and vaccine application of gE with other proteins of the virus. This article reviews the structure of gE, the relationship between gE and other proteins of the virus, and the application of gE in vaccinology, which provides useful information for further research on gE.

IntroductionAs the presence of hepatic metastases is very important to cancer patients' clinical stage which would directly affect the selection and application of anti-cancer treatments. Although conventional ultrasound is commonly performed as a screening tool, most of the examinations have relatively poor sensitivity and specificity for detecting liver metastases. Contrast-enhanced ultrasound (CEUS) with Sonazoid has been reported to have the advantage of the diagnosis and therapeutic support of focal hepatic lesions and its specific Kupffer phase whole liver scan (KPWLS) is believed to be sensitive to detect liver metastases. And the purpose of this study is to determine the number, size, location and diagnosis of metastatic lesions, and to compare the results with conventional ultrasound and contrast-enhanced computed tomography (CECT), thus to clarify the application value, indications of Sonazoid-CEUS in screening liver metastasis.Methods and analysisKupffer phase whole liver scan for metastases (KPWLSM) is a self-control, blind map-reading, single-center, prospective superiority trial. Approved by the institutional review committee, the study period is planned to be from 1 January 2022 to 31 December 2025. Our study will include 330 patients with history of malignant tumors that cling to metastasize to liver. All patients will undergo the examinations of conventional ultrasound, Sonazoid-CEUS, and contrast-enhanced magnetic resonance imaging (CEMRI), and 65 of them should have additional CECT scans. The primary endpoint is the comparative analysis of the numbers of detected liver metastatic lesions among Sonazoid-CEUS, conventional ultrasound and CECT in screening liver metastases. Subjective conditions of patient after injection of Sonazoid will be followed up 3 and 30 days after KPWLSM, and any short-term and long-term adverse events are to be recorded with telephone interviews.Ethics and disseminationThis study has been granted by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Approval No: 2021-197). When the KPWLSM is completed, we will publish it in an appropriate journal to promote further widespread use.RegistrationTrial Registration Number and Date of Registration: Chinese Clinical Trial Registry, ChiCTR2100054385, December 16, 2021.

Cosmetic skin diseases are a part of many dermatological concerns brought up by patients, which negatively affect mental health and quality of life. Imaging technology has an established role in the diagnosis of cosmetic skin diseases by recognizing information on deep skin lesions. Due to the complex physiological and pathological nature of cosmetic skin diseases, the diagnostic imaging performance varies greatly. Developing noninvasive technology models with wide applicability, particularly high-frequency ultrasound (HFUS), which is able to achieve high-resolution imaging of the skin from the stratum corneum down to the deep fascia, is of great significance to medical cosmetology. To explore the great potential of HFUS in cosmetic skin diseases, a narrative review of literature from PubMed and Web of Science published between 1985 and 2022 was conducted. This narrative review focuses on the progression of HFUS imaging in medical cosmetology, especially on its promising application in the quantitative evaluation and differential diagnosis of cutaneous pathological scar, port wine stain (PWS), acne, skin aging, and other cosmetic applications.

Abstract Although water‐soluble graphene quantum dots (GQDs) have shown various promising bio‐applications due to their intriguing optical and chemical properties, the large heterogeneity in compositions, sizes, and shapes of these GQDs hampers the better understanding of their structure‐properties correlation and further uses in terms of large‐scale manufacturing practices and safety concerns. It is shown here that a water‐soluble atomically‐precise GQD (WAGQD‐C96) is synthesized and exhibits a deep‐red emission and excellent sonodynamic sensitization. By decorating sterically hindered water‐soluble functional groups, WAGQD‐C96 can be monodispersed in water without further aggregation. The deep‐red emission of WAGQD‐C96 facilitates the tracking of its bio‐process, showing a good cell‐uptake and long‐time retention in tumor tissue. Compared to traditional molecular sonosensitizers, WAGQD‐C96 generates superior reactive oxygen species and demonstrates excellent tumor inhibition potency as an anti‐cancer sonosensitizer in in vivo studies. A good biosafety of WAGQD‐C96 is validated in both in vitro and in vivo assays.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.

The herpesvirus UL11 protein is encoded by the UL11 gene and is a membrane-anchored protein with multiple functions. In the last stage of viral replication, UL11 participates in the secondary envelopment process. It also plays a key role in primary envelopment, the transportation of newly assembled viral particles through cytoplasmic vesicles, and virion egress from the cell. UL11 is an important accessory protein and sometimes cooperates with other proteins that participate in virus-induced cell fusion. Cell fusion is necessary for cell-to-cell transmissions. This review summarizes the latest literature and discusses the roles of UL11 in viral assembly, primary and secondary envelopment, and cell-to-cell transmission to obtain a better understanding of the UL11 protein in the life cycle of herpesviruses and to serve as a reference for studying other viruses. Additionally, some recently discovered characteristics of UL11 are summarized.

Duck plague virus (DPV), a member of the alphaherpesvirus subfamily, can cause severe damage and immunosuppression in ducks and geese in China. Since lacking an available cell model, the antiviral signal transduction pathways induction and regulation mechanisms related to DPV infection in duck cells are still enigmatic. Our previous study developed a monocyte/macrophages cell model, which has been applied to study innate immunity with DPV. In the present study, we compared and analyzed transcriptome associated with the DPV infection of CHv (virulent strain) and CHa (avirulent strain) at 48hpi based on the duck monocyte/macrophages cell model and RNA-seq technology. Differentially expressed genes (DEGs) analysis showed 2,909 and 2,438 genes altered in CHv and CHa infected cells compared with control cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were mainly involved in biological processes such as metabolic pathways, viral infectious diseases, immune system, and signal transduction. The CHv and CHa virus differentially regulated MAPK, NF-κB, and IFN signaling pathways based on transcriptome sequencing data and RT-qPCR results. The JNK inhibitor SP600125 enhanced the IFN signaling, but potentially reduced the VSV and DPV titers in the cell culture supernatant, indicating that JNK negatively regulates the IFN pathway and the inflammatory pathway to promote virus proliferation. The research results may provide promising information to understand the pathogenesis of DPV and provide a novel mechanism by which DPV modulates antiviral signaling and facilitate virus proliferation through hijacking the JNK pathway, which provides a new means for the prevention and control of DPV infection.

ObjectiveTo explore the interrelationship between post-traumatic stress symptoms (PTSS), illness uncertainty (IU), and anticipatory grief (AG).MethodsStructural equation modeling with bootstrapping estimation was conducted using data from a convenience sample of 254 family caregivers of patients with advanced lung cancer in China. Participants were recruited from a public cancer hospital in Shenyang, China. The family caregivers completed the Impact of Events Scale-Revised, Uncertainty in Illness Scale Family Caregiver Version, and Anticipatory Grief Scale.ResultsThe measurement model has good reliability and validity, and the final model fit the data well. PTSS positively influenced AG (direct effect estimate = 0.391, p = 0.002). Moreover, IU was found to mediate the relationship between PTSS and AG (Indirect effects estimate = 0.168, p = 0.005). The mediating effect of IU accounted for up to 30.1% of the total effect.ConclusionIU mediated the relationship between PTSS and AG. Healthcare professionals should continuously assess PTSS, IU and AG levels in FCs and provide effective intervention options for mitigation.

Host translation is generally modulated by viral infection, including duck hepatitis A virus (DHAV) infection. Previously, we reported that cellular protein synthesis in a cell model of duck embryo fibroblasts is significantly inhibited by DHAV infection but not viral proteins, suggesting that an important viral-host interaction occurs at the translational level. In this study, we aim to further understand the impact of DHAV virulence on cellular N6-methyladenosine (m6A) modification, which is essential to a wide variety of RNA biological processes, such as mRNA stabilization and translation. Using m6A antibody-based immunoprecipitation, m6A-seq, and LC–MS/MS, we observed that m6A-modified mRNA exists in both virulent and attenuated DHAV-infected duckling livers. Importantly, m6A levels in mRNA were much higher in attenuated DHAV-infected livers compared with virulent DHAV-infected livers, suggesting virulence-dependent regulation of m6A modification. Analysis of modification motifs indicated that GAAGAAG is the most enriched motif. Combined m6A-seq and RNA-seq data analysis indicated a generally positive correlation between m6A and mRNA expression levels in DHAV-infected duckling livers. GO analysis of genes with decreased or increased m6A levels showed that these genes were enriched in various terms, including oxidation–reduction processes and antiviral immune responses. Collectively, our work reveals DHAV virulence-dependent coordination between m6A modification and mRNA expression in duckling livers.

ABSTRACT: To investigate the pivotal roles of the duck plague virus (DPV) tegument protein UL14 in viral replication, we generated 2 mutated viruses of DPV by using the bacterial artifcial chromosome system, the UL14-null mutant virus (CHv-BAC-ΔUL14) and the corresponding revertant virus (CHv-BAC-ΔUL14R). We found that the CHv-BAC-ΔUL14 viruses exhibited impaired virion morphogenesis in transmission electron microscopy (TEM) studies. Furthermore, CHv-BAC-ΔUL14 exhibited a plaque size reduction in duck embryo fibroblasts (DEFs). Finally, CHv-BAC-ΔUL14 exhibited a significant viral growth defect. Taken together, our findings suggest that DPV UL14 protein regulates viral morphogenesis for efficient viral replication.

Abstract Background NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. Methods NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. Results NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. Conclusions We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

Abstract Extensive decoration of backbones is a major factor resulting in resistance of enzymatic conversion in hemicellulose and other branched polysaccharides. Employing debranching enzymes is the main strategy to overcome this kind of recalcitrance at present. A carbohydrate-binding module (CBM) is a contiguous amino acid sequence that can promote the binding of enzymes to various carbohydrates, thereby facilitating enzymatic hydrolysis. According to previous studies, CBMs can be classified into four types based on their preference in ligand type, where Type III and IV CBMs prefer to branched polysaccharides than the linear and thus are able to specifically enhance the hydrolysis of substrates containing side chains. With a role in dominating the hydrolysis of branched substrates, Type III and IV CBMs could represent a non-catalytic approach in overcoming side-chain recalcitrance.

Abstract Iron is essential for most bacteria to survive, but excessive iron leads to damage by the Fenton reaction. Therefore, the concentration of intracellular free iron must be strictly controlled in bacteria. Riemerella anatipestifer (R. anatipestifer), a Gram-negative bacterium, encodes the iron uptake system. However, the iron homeostasis mechanism remains largely unknown. In this study, it was shown that compared with the wild type R. anatipestifer CH-1, R. anatipestifer CH-1Δfur was more sensitive to streptonigrin, and this effect was alleviated when the bacteria were cultured in iron-depleted medium, suggesting that the fur mutant led to excess iron accumulation inside cells. Similarly, compared with R. anatipestifer CH-1∆recA, R. anatipestifer CH-1∆recAΔfur was more sensitive to H2O2-induced oxidative stress when the bacteria were grown in iron-rich medium rather than iron-depleted medium. Accordingly, it was shown that R. anatipestifer CH-1∆recAΔfur produced more intracellular ROS than R. anatipestifer CH-1∆recA in iron-rich medium. Electrophoretic mobility shift assays showed that R. anatipestifer CH-1 Fur suppressed the transcription of putative iron uptake genes through binding to their promoter regions. Finally, it was shown that compared with the wild type, R. anatipestifer CH-1Δfur was significantly attenuated in ducklings and that the colonization ability of R. anatipestifer CH-1Δfur in various tissues or organs was decreased. All these results suggested that Fur is important for iron homeostasis in R. anatipestifer and its pathogenic mechanism.

With the development of combined cycle engines, it is urgent to estimate more quickly and accurately the flow capture capacity and starting performance of variable geometry inlets over a wide Mach number range. Based on the flow field and parameter fitting, two prediction methods for the curved axisymmetric inlet with lip translation scheme have been proposed. The method based on the flow field of the reference inlet is more efficient than the parameters-based prediction method, as it can accurately predict the lip translation distance and the corresponding flow coefficient over the entire working range of the inlet without additional numerical calculations. Moreover, the starting Mach number is accurately predicted by the fitting method based on the throat Mach number of the reference inlet, with a relative error of only 0.95% compared to the numerical simulation. The flow coefficient-based method is simple and accurate for predicting lip translation distances with a known starting Mach number, with a relative error of only 1.65% compared to numerical simulations. The prediction approaches can overcome the drawbacks of the standard iterative algorithms and significantly enhance computational accuracy and efficiency.

A monopost seat is a novel, lightweight seat developed to utilize most of the interior space of vehicles. The space under the seat can be utilized by inserting a monopost columnar structure between a monopost seat rail and the floorboard. This design increases the perceived spaciousness of the vehicle and imparts passengers with a higher degree of freedom, because the seats can be adjusted more easily than standard seats. Meeting these requirements will require the seats to be sufficiently strong and sturdy in order to maintain passenger safety. Compared to traditional seats, it is more likely that a monopost seat will shift under the mass of the passenger, and these seats are more vulnerable to external vehicle collisions. Passenger safety is further compromised if an operational function is added. Therefore, further research on monopost seats is required. This study performed quasi-static and dynamic simulations to determine if the attachment of monopost seats to a vehicle meets international safety requirements in collision events. With a focus on clarifying the dynamic simulation process, the outcomes of quasi-static simulations were compared with the results obtained from dynamic simulations.

As a widely implemented irrigation regime for paddy fields, water-saving irrigation (WSI) is capable of ensuring water resource security and improving nitrogen use efficiency (NUE). Higher gaseous nitrogen losses (GNL) lead to a low recovery rate of basal nitrogen, and this is the primary reason that restricts further improvements in the NUE under WSI. The deep placement of nitrogen fertilizer (DPN) is considered an efficient agricultural management measure to reduce GNL. However, the effects of WSI combined with the deep placement of basal nitrogen fertilizer on NUE, GNL, and rice yield in paddy fields remain largely unknown. In this study, a 2-year field experiment was conducted to measure GNL (N2O emissions and NH3 volatilization), NUE, and rice yield. Four treatments were utilized: (i) conventional flooding irrigation + broadcast of nitrogen fertilizer (110 kg N hm−2, CFN); (ii) water-saving irrigation + deep placement of basal nitrogen fertilizer (110 kg N hm−2, WSN); (iii) water-saving irrigation + deep placement of basal nitrogen fertilizer (99 kg N hm−2, WSN1); (iv) water-saving irrigation + deep placement of basal nitrogen fertilizer (88 kg N hm−2, WSN2). The results showed that the GNL in paddy fields under treatment ranged from 5.29 to 10.67 kg hm−2. Deep placement of basal nitrogen fertilizer mitigated the GNL of the paddy fields under WSI. The GNL of CFN was significantly higher than those of WSN1 and WSN2 by 26.9% and 54.0% in 2021 and 14.4% and 23.3% in 2022, respectively (p < 0.05). Under WSI, the deep placement of basal nitrogen fertilizer reduced the GNL primarily via the reduction of NH3 volatilization. NH3-N of CFN was higher than those treatments under WSI. The rice yield of CFN was significantly lower than those of WSN and WSN1 by 22.4% and 21.6% in 2021 and 4.6% and 1.5% in 2022, respectively. (p < 0.05). Moreover, the NUE of each treatment under WSI was higher than that of CFN. These changes exhibited similar trends in 2021 and 2022. These results demonstrated that deep placement of basal nitrogen fertilizer is an effective practice to ensure food and environmental security under WSI.

Duck enteritis virus (DEV) multifunctional tegument protein UL13 is predicted to be a conserved herpesvirus protein kinase; however, little is known about its subcellular localization signal. In this study, through transfection of 2 predicted nuclear signals of DEV UL13 fused to enhanced green fluorescent protein, 2 bipartite nuclear localization signals (NLS) were identified. We found that ivermectin blocked the NLS-mediated nuclear import of DEV UL13, showing that the nuclear localization signal of DEV UL13 is a classical importin α- and β-dependent process. We constructed a DEV UL13 mutant strain in which the NLS of DEV UL13 was deleted to explore whether deletion of the NLS affects viral replication. Amino acids 4 to 7 and 90 to 96 were predicted to be NLSs, further proving that nuclear import occurs via a classical importin α- and β-dependent process. We also found that the NLS of pUL13 had no effect on DEV replication in cell culture. Our study enhances the understanding of DEV pUL13. Taken together, these results provide significant information regarding the biological function of pUL13 during DEV infection.

We present an numerical and experimental analysis of a Yb:YAG thin disk regenerative amplifier. Group velocity dispersion, third order dispersion, and self-phase modulation (SPM) effects are considered in the simulations of the amplification process. By virtue of the simulations, a compact femtosecond Yb:YAG thin-disk chirped-pulse regenerative amplifier delivering an average power of 50 W at a central wavelength of 1030 nm with a propagation factor of M2 < 1.4 at a repetition rate of 200 kHz and a pulse duration of 500 fs was constructed. Numerical simulation based on this Yb:YAG thin-disk was carried out to investigate the pulse parameters evolution in each round trip. The measured experimental results in pulse width, spectrum, and pulse energy together fitted quite well with the numerical simulation. This plays an important role in the design of high-peak-power regenerative amplifier and will facilitate further power scaling and suppression of gain narrowing of the whole system.

To determine the role of glycoprotein I (gI) in duck plague virus (DPV), a gI-deleted mutant (BAC-CHv-ΔgI) and a gI-revertant virus (BAC-CHv-ΔgI Rev) were constructed by using a markerless two-step Red recombination system implemented on the DPV genome cloned into a bacterial artificial chromosome (BAC). Mutants were characterized on duck embryo fibroblast (DEF) cells compared with wild-type virus. BAC-CHv-ΔgI produced viral plaques on DEF cells that were on average approximately 57.2% smaller than those produced by BAC-CHv-ΔgI Rev and wild-type virus. Electron microscopy confirmed that deleting of gI resulted in nucleocapsids accumulated around the cytoplasm vesicles and few of them could complete the final envelopment process. These results clearly indicated that DPV gI plays significant roles in viral cell-cell spread and viral final envelopment process.

Abstract Background The use of a self-expandable metallic stent (SEMS) as a bridge to surgery has increased for patients with obstructing colorectal cancer. However, relatively few reports have compared SEMS as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC) vs. emergency surgery (ES). This study aimed to evaluate the benefits of elective surgery after SEMS placement vs. ES for patients (including stage IV cases) with acute MORC. Methods Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups. Results In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. Also, there was no significant difference in PFS and OS rates between patients with stage II and III colon cancer. After colectomy for synchronous liver metastases among stage IV patients, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs. combined resection was 3.258 (95% CI 0.858–12.370; P = 0.041). Conclusion Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.

Duck plague (DP) is an acute infectious disease in the duck industry. The duck plague virus (DPV) is the pathogen, a subfamily of alphaherpesvirinae. gE is a type I membrane protein that contains three parts: an extracellular domain, a transmembrane domain, and a cytoplasmic domain. gE is the major virulence determinant of α-herpesvirus. However, the functions of the gE extracellular and cytoplasmic domains have not been reported in DPV. In this study, a gE extracellular domain deletion mutant and a gE cytoplasmic domain deletion mutant were constructed from DPV. Virus replication kinetics showed that the growth titers of both the gE ectodomain-deleted mutant virus and the gE cytoplasmic domain-deleted virus in DEFs were lower than that of the parental virus CHv-50. DPV CHv-gEΔET and DPV CHv-gEΔCT were continuously passed to the 20th passage in DEFs and the 10th in ducklings. The mutant virus DNA after passage was extracted for identification. The results showed that the gE ectodomain and gE cytoplasmic domain deletion mutant viruses have good genetic stability. The ducklings in each group (n=10) were inoculated with the same titers of DPV CHv-gEΔET, DPV CHv-gEΔCT, DPV CHv-ΔgE, and parental CHv-50, respectively. Clinical symptoms and serum antibody levels were detected after inoculation. The results showed that the virulence of DPV CHv-gEΔCT to ducklings was reduced compared with parental CHv-50, while the virulence of DPV CHv-gEΔET to ducklings was significantly reduced. 105 TCID50 DPV CHv-gEΔET or DPV CHv-ΔgE can induce ducklings to produce DPV-specific antibodies, protect the ducklings from virulent CHv challenge. Therefore, DPV CHv-gEΔET may serve as a promising vaccine candidate to prevent and control duck plague.

Dysfunction of protein trafficking has been intensively associated with neurological diseases, including neurodegeneration, but whether and how protein transport contributes to oligodendrocyte (OL) maturation and myelin repair in white matter injury remains unclear. ER-to-Golgi trafficking of newly synthesized proteins is mediated by coat protein complex II (COPII). Here, we demonstrate that the COPII component Sec13 was essential for OL differentiation and postnatal myelination. Ablation of Sec13 in the OL lineage prevented OPC differentiation and inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), while improving protein trafficking by tauroursodeoxycholic acid (TUDCA) or ectopic expression of COPII components accelerated myelination. COPII components were upregulated in OL lineage cells after demyelinating injury. Loss of Sec13 altered the secretome of OLs and inhibited the secretion of pleiotrophin (PTN), which was found to function as an autocrine factor to promote OL differentiation and myelin repair. These data suggest that Sec13-dependent protein transport is essential for OL differentiation and that Sec13-mediated PTN autocrine signaling is required for proper myelination and remyelination.

ObjectiveTo examine the relations between social support, illness uncertainty (IU), and fear of cancer recurrence (FCR).MethodsUsing data from a convenience sample of 231 breast cancer survivors in China to perform structural equation modeling with bootstrapping estimation. Participants were recruited from a general hospital in Shenyang, China. Participants completed the Perceived Social Support Scale, Mishel Uncertainty in Illness Scale, and Fear of Cancer Recurrence Inventory- Shorter Form.ResultsThe majority of breast cancer survivors have FCR (67.5%). FCR was significantly negatively associated with social support, and was significantly positively associated with IU (both P < 0.01). Moreover, IU was found to mediate the relationship between social support and FCR (standardized indirect effect = –0.18; bias-corrected 95% confidence interval: –0.255, –0.123).ConclusionThe findings support the final model. Good social support can directly mitigate FCR, while illness uncertainty can play a mediation role between social support and FCR. Further studies should be conducted to explore effective interventions for social support and IU to ultimately mitigate FCR in cancer survivors.

Abstract Duck enteritis virus (DEV) is a member of the Alphaherpesvirinae subfamily. The characteristics of some DEV genes have been reported. However, information regarding the DEV UL47 gene is limited. In this study, we identified the DEV UL47 gene encoding a late structural protein located in the nucleus of infected cells. We further found that two domains of DEV pUL47, amino acids (aa) 40 to 50 and 768 to 777, could function as nuclear localization sequence (NLS) to guide the nuclear localization of pUL47 and nuclear translocation of heterologous proteins, including enhanced green fluorescent protein (EGFP) and beta-galactosidase (β-Gal). Moreover, pUL47 significantly inhibited polyriboinosinic:polyribocytidylic acid [poly(I:C)]-induced interferon beta (IFN-β) production and downregulated interferon-stimulated gene (ISG) expression, such as Mx and oligoadenylate synthetase-like (OASL), by interacting with signal transducer and activator of transcription-1 (STAT1).

Nested polyhedra are compelling but incredibly complex synthetic targets in cluster chemistry. Here, the authors synthesize a Ag90 nanocluster comprising three concentric polyhedra with apparently incompatible octahedral (Oh) and icosahedral (Ih) symmetry, a mathematical oddity that is solved by the shells’ symmetric arrangement around rotational 2- and 3-fold axes.

Abstract Background Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses. Main body The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion. Conclusions Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.

Abstract Calcium dysregulation is a key pathological event in Alzheimer’s disease (AD). In studying approaches to mitigate this calcium overload, we identified the collapsin response mediator protein 2 (CRMP2), an axonal guidance protein that participates in synapse dynamics by interacting with and regulating activity of N-methyl-D-aspartate receptors (NMDARs). We further identified a 15 amino acid peptide from CRMP2 (designated CBD3, for calcium-binding domain 3), that reduced NMDAR-mediated Ca2+ influx in cultured neurons and post-synaptic NMDAR-mediated currents in cortical slices. Whether targeting CRMP2 could be therapeutically beneficial in AD is unknown. Here, using CBD3, we tested the utility of this approach. Employing the APP/PS1 mouse model of AD which demonstrates robust pathophysiology including Aβ1–42 deposition, altered tau levels, and diminished cognitive functions, we asked if overexpression of CBD3 could rescue these events. CBD3 was engineered into an adeno-associated vector and nasally delivered into APP/PS1 mice and then biochemical (immunohistochemistry, immunoblotting), cellular (TUNEL apoptosis assays), and behavioral (Morris water maze test) assessments were performed. APP/PS1 mice administered adeno-associated virus (AAV, serotype 2) harboring CBD3 demonstrated: (i) reduced levels of Aβ1–42 and phosphorylated-tau (a marker of AD progression), (ii) reduced apoptosis in the hippocampus, and (iii) reduced cognitive decline compared with APP/PS1 mice or APP/PS1 administered a control virus. These results provide an instructive example of utilizing a peptide-based approach to unravel protein-protein interactions that are necessary for AD pathology and demonstrate the therapeutic potential of CRMP2 as a novel protein player in AD.