TM7SF2-induced lipid reprogramming promotes cell proliferation and migration via CPT1A/Wnt/ß-Catenin axis in cervical cancer cells.

Cervical cancer poses a serious threat to women's health globally. Our previous studies found that upregulation of TM7SF2, which works as an enzyme involved in the process of cholesterol biosynthesis expression, was highly correlated with cervical cancer. However, the mechanistic basis of TM7SF2 promoting cervical cancer progression via lipid metabolism remains poorly understood. Therefore, quantification of fatty acids and lipid droplets were performed in vitro and in vivo. The protein-protein interaction was verified by Co-IP technique. The mechanism and underlying signaling pathway of TM7SF2 via CPT1A associated lipid metabolism in cervical cancer development were explored using Western blotting, IHC, colony formation, transwell assay, and wound healing assay. This study reported that overexpression of TM7SF2 increased fatty acids content and lipid droplets both in vivo and in vitro experiments. While knockout of TM7SF2 obviously attenuated this process. Moreover, TM7SF2 directly bonded with CPT1A, a key enzyme in fatty acid oxidation, and regulated CPT1A protein expression in cervical cancer cells. Notably, the proliferation and metastasis of cervical cancer cells were elevated when their CPT1A expression was upregulated. Then, rescue assay identified that CPT1A overexpressed could enhance the cell viability and migration in TM7SF2-knockout cells. Furthermore, depletion of TM7SF2 significantly inhibited WNT and ß-catenin proteins expression, which was enhanced by CPT1A-overexpressed. The proliferation and migration of cervical cancer cells were reversed in CPT1A-overexpressed cells with the treatment of MSAB, an inhibitor of Wnt/ß-Catenin pathway. This study put forward an idea that TM7SF2-induced lipid reprogramming promotes proliferation and migration via CPT1A/Wnt/ß-Catenin axis in cervical cancer, underlying the progression of cervical cancer.

Therapeutic application of manganese-based nanosystems in cancer radiotherapy.

Radiotherapy is an important therapeutic modality in the treatment of cancers. Nevertheless, the characteristics of the tumor microenvironment (TME), such as hypoxia and high glutathione (GSH), limit the efficacy of radiotherapy. Manganese-based (Mn-based) nanomaterials offer a promising prospect for sensitizing radiotherapy due to their good responsiveness to the TME. In this review, we focus on the mechanisms of radiosensitization of Mn-based nanosystems, including alleviating tumor hypoxia, increasing reactive oxygen species production, increasing GSH conversion, and promoting antitumor immunity. We further illustrate the applications of these mechanisms in cancer radiotherapy, including the development and delivery of radiosensitizers, as well as their combination with other therapeutic modalities. Finally, we summarize the application of Mn-based nanosystems as contrast agents in realizing precision therapy. Hopefully, the present review will provide new insights into the biological mechanisms of Mn-based nanosystems, as well as their applications in radiotherapy, in order to address the difficulties and challenges that remain in their clinical application in the future.

Plant Polyphenol Pyrogallol and Polyamine-Based Co-Deposition for High-Efficiency Nanofiltration Membrane Preparation towards Inorganic Salt Removal.

The co-deposition between polyphenols and amines has been demonstrated in order to prepare positively charged nanofiltration (NF) membranes for multivalent cation rejection in recent years; however, the low reactivities of the involved polyphenols usually cause a long co-deposition time and unsatisfactory rejection. Herein, a novel plant polyphenol (PG) was co-deposited with tetraethylenepentamine (TEPA) in a much shorter time period to prepare positively charged NF with high multivalent cation rejection membranes. The performance of the co-deposition membranes can be easily controlled by adjusting the mass ratio of PG and TEPA, reaction time, and pH value of the buffer solution. The optimal membrane, prepared under a polyphenol and polyamine mass ratio of 1:1, coating time of 2 h, and pH value of 8.0, shows a decent pure water permeability of 8.43 L m-2 h-1 bar-1 while maintaining a superior 96.24% MgCl2 rejection. More importantly, the universality of this method was corroborated by employing other amines with different molecular weights in the co-deposition. This work provides new insights for the preparation of high-performance positively charged NF membranes.

Interaction of SERINC5 and IFITM1/2/3 regulates the autophagy-apoptosis-immune network under CSFV infection.

The host restriction factor serine incorporator 5 (SERINC5) plays a key role in inhibiting viral activity and has been shown to inhibit classical swine fever virus (CSFV) infection. However, the action of SERINC5 in the interaction between host cells and CSFV remains poorly understood. This study found that SERINC5 represses CSFV-induced autophagy through MAPK1/3-mTOR and AKT-mTOR signalling pathways. Further research showed that SERINC5 promotes apoptosis by repressing autophagy. Likewise, it was demonstrated that SERINC5 interacting proteins IFITM1/2/3 inhibit CSFV replication and regulate autophagy in a lysosomal-associated membrane protein LAMP1-dependent manner. In addition, IFITM1/2/3 interference promotes the NF-κB signalling pathway for potential immunoregulation by inhibiting autophagy. Finally, the functional silencing of IFITM1/2/3 genes was demonstrated to enhance the inhibitory effect of SERINC5 on autophagy. Taken together, These data uncover a novel mechanism through SERINC5 and its interacting proteins IFITM1/2/3, which mediates CSFV replication, and provides new avenues for controlling CSFV.

Lipid transfer proteins involved in plant-pathogen interactions and their molecular mechanisms.

Nonspecific lipid transfer proteins (LTPs) are small, cysteine-rich proteins that play numerous functional roles in plant growth and development, including cutin wax formation, pollen tube adhesion, cell expansion, seed development, germination, and adaptation to changing environmental conditions. LTPs contain eight conserved cysteine residues and a hydrophobic cavity that provides a wide variety of lipid-binding specificities. As members of the pathogenesis-related protein 14 family (PR14), many LTPs inhibit fungal or bacterial growth, and act as positive regulators in plant disease resistance. Over the past decade, these essential immunity-related roles of LTPs in plant immune processes have been documented in a growing body of literature. In this review, we summarize the roles of LTPs in plant-pathogen interactions, emphasizing the underlying molecular mechanisms in plant immune responses and specific LTP functions.

The roles of gold and silver nanoparticles on ZnIn2S4/silver (gold)/tetra(4-carboxyphenyl)porphyrin iron(III) chloride hybrids in carbon dioxide photoreduction.

The construction of hybrid catalysts composed of inorganic semiconductors and molecular catalysts shows great potential for achieving high photocatalytic carbon dioxide (CO2) conversion efficiency. In this study, ZnIn2S4 was first synthesized via a solvothermal route. Gold (Au) and silver (Ag) nanoparticles were then deposited on ZnIn2S4 via the reduction of noble metal precursor by sulfur vacancy defects. The obtained composite was further combined with tetra(4-carboxyphenyl)porphyrin iron(III) chloride (FeTCPP) molecular catalyst for efficient photocatalytic CO2 conversion. The roles of different noble metal nanoparticles in charge separation and interfacial electron transfer have been comprehensively studied. The photocatalytic performance and photoelectrochemical characterizations demonstrate that the introduction of Ag or Au nanoparticles is beneficial for charge separation. More importantly, the presence of Ag nanoparticles plays a crucial role in promoting the interfacial charge transfer between ZnIn2S4 and FeTCPP, whereas, Au nanoparticles function as active sites for the water reduction reaction.

Epidemiological investigation of duck adenovirus 3 in southern China, during 2018-2020.

RESEARCH HIGHLIGHTSFirst report of the epidemiology of duck adenovirus 3 infection in China.Mutant DAdV-3 strains (truncated ORF67) became predominant.

Extracellular vesicles: Their functions in plant-pathogen interactions.

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well-studied functions in mammalian systems, including cell-to-cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant-pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence-related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram-negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern-recognition receptor- and BRI1-ASSOCIATED RECEPTOR KINASE- and SUPPRESSOR OF BIR1-mediated signalling pathways, and salicylic acid-dependent and -independent processes. The roles of EVs in plant-pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs.

Isolation and characterization of a novel chicken astrovirus in China.

Chicken astrovirus (CAstV) is associated with kidney disease and visceral gout, runting and stunting syndrome, and white chick hatchery disease, causing economic losses to the poultry industry worldwide. In this study, 55.6% of 36 clinical samples from Guangdong province in China were positive for CAstV, but negative for other common enteric viruses, including avian nephritis virus, infectious bronchitis virus, fowl adenovirus Group I, Newcastle disease virus, chicken parvovirus, reovirus, and rotavirus by PCRs and RT-PCRs. A CAstV strain, named GD202013, was isolated from Guangdong province in south China, and was identified by CAstV RT-PCR. A whole genome sequence analysis demonstrated that GD202013 shares 76.0 to 88.1% identity with 24 reference strains in GenBank. Phylogenetic analysis, based on whole genome and capsid protein, showed that GD202013 is more closely related to 2 US strains (GA2011/US/2011 and 4175/US/2011) belonging to subgroup Bii. Recombination analysis indicated that GD202013 is a recombinant strain formed by 3 strains: a major parent strain CkP5/US/2016, and 2 minor parent strains (GA2011/US/2011 and G059/PL/2014). In addition, the chicken embryo infection experiment demonstrated that GD202013 causes hatchability reduction, growth depression, and death of embryos. Macroscopic and microscopic lesions in the liver, kidney and small intestine were observed in the dead-in-shell embryos. This is the first report of the novel CAstV infection in China.

Wireless Self-Powered High-Performance Integrated Nanostructured-Gas-Sensor Network for Future Smart Homes.

The accelerated evolution of communication platforms including Internet of Things (IoT) and the fifth generation (5G) wireless communication network makes it possible to build intelligent gas sensor networks for real-time monitoring chemical safety and personal health. However, this application scenario requires a challenging combination of characteristics of gas sensors including small formfactor, low cost, ultralow power consumption, superior sensitivity, and high intelligence. Herein, self-powered integrated nanostructured-gas-sensor (SINGOR) systems and a wirelessly connected SINGOR network are demonstrated here. The room-temperature operated SINGOR system can be self-driven by indoor light with a Si solar cell, and it features ultrahigh sensitivity to H2, formaldehyde, toluene, and acetone with the record low limits of detection (LOD) of 10, 2, 1, and 1 ppb, respectively. Each SINGOR consisting of an array of nanostructured sensors has the capability of gas pattern recognition and classification. Furthermore, multiple SINGOR systems are wirelessly connected as a sensor network, which has successfully demonstrated flammable gas leakage detection and alarm function. They can also achieve gas leakage localization with satisfactory precision when deployed in one single room. These successes promote the development of using nanostructured-gas-sensor network for wide range applications including smart home/building and future smart city.

Prevalence of HPV infections in surgical smoke exposed gynecologists.

OBJECTIVES: Human papillomavirus (HPV) has been reported recently in surgical smoke generated by gynecological operations. The objective of this study was to investigate whether gynecologists who have performed electrosurgery including loop electrosurgical excision procedure (LEEP), are at risk of acquiring HPV DNA through surgical smoke. METHODS: A related questionnaire was designed and 700 gynecologist nasal swab samples were collected in 67 hospitals. In addition, the flow fluorescence hybridization technique was used to detect HPV DNA, and the Chi-square test was applied to analyze whether related risk factors including electrical surgery, were correlated with HPV infection in surgeons' nasal epithelial cells. RESULTS: The HPV infection rate in the nasal epithelial cells of the participants who performed electrosurgery (8.96%, 42/469) or LEEP (10.11%, 36/356) was significantly higher than that in the remaining participants who did not perform electrosurgery (1.73%, 4/231) or LEEP (2.91%, 10/344), respectively. The most prevalent HPV genotype in the electrosurgery group was HPV16 (76.19%, 32/42). The HPV-positive rate was increased in the group that had a longer duration of electrosurgery (P = 0.016). Additionally, the HPV detection rate was significantly lower in electrosurgery operators who used surgical mask (7.64%, 33/432) than in those who did not use protective masks (24.32%, 9/37). Furthermore, the N95 mask (0%, 0/196) significantly reduced the risk for HPV infection compared to that with the general mask (13.98%, 33/236, P < 0.001). Furthermore, 46 participants infected with HPV were followed-up for 3-24 months, and approximately 43.48% (20/46) and 100% (41/41) became negative for HPV DNA, respectively. CONCLUSIONS: Gynecologists who performed electrosurgery including LEEP were at risk of acquiring HPV infection. Surgical masks, especially the N95 mask, significantly decreased the hazard of HPV transmission from surgical smoke.

Isolation and Characterization of A Novel Fowl Adenovirus Serotype 8a Strain from China.

Since 2012, the clinical cases of inclusion body hepatitis showed an increasing trend in China, causing considerable economic losses to the poultry industry. In this study, a fowl adenovirus strain CH/GDLZ/201801 was isolated from a chicken flock experiencing inclusion body hepatitis and analyzed by complete genome sequencing. The pathogenicity of the new virus strain was examined by experimental infection of specific pathogen free chickens. The isolate was identified by immunofluorescence and the virions presented typical icosahedral particles under transmission electron microscopy. The full genome of the isolate was 44,329 nucleotides in length with 58% G+C content. Phylogenetic analysis, based on the whole genome, revealed that the new isolate was closest to serotype 8a from the species Fowl aviadenovirus E (FAdV-E). Recombination analysis and phylogenetic analysis showed that the new isolate is a recombinant strain between FAdV-8a and FAdV-8b. In infection experiments, three infected chickens showed clinical signs and one chicken died on day 7 post infection, corresponding to 5% mortality. Macroscopic and microscopic lesions in the liver were observed, and viral antigen could be detected in the livers by immunohistochemical staining and TEM. Taken together, our study describes the genomic characteristics and pathogenicity of a FAdV-8a strain in China. It would lay a solid foundation for further study of the pathogenic mechanism and vaccine development of the virus.

Fabrication of high-performance composite nanofiltration membranes for dye wastewater treatment: mussel-inspired layer-by-layer self-assembly.

Inspired by the mussel adhesion mechanism, plant polyphenol tannic acid (TA) with abundant catechol groups and hydrophilic Jeffamine (JA) containing amino groups were used in a layer-by-layer (LBL) process to fabricate composite nanofiltration (NF) membranes in this study. Alternately immersing a polyacrylonitrile substrate into individual TA and JA buffer solutions could readily construct a NF membrane selective layer without any pre-treatment to the substrate. The optimised membrane showed a high pure water permeance of 37 L m-2 h-1 bar-1 whilst maintaining rejections higher than 90% towards various dyes with molecular weights ranging from 269 to 1017 g mol-1. Particularly, the obtained membrane exhibited excellent anti-fouling and long-term performance attributed to the hydrophilic membrane surface and covalent bonds in the selective layer. The novel strategy inherited the advantages of a mussel-inspired dopamine material but overcame its disadvantages. The results disclosed in this study not only provide a novel strategy to prepare composite NF membranes, but also facilitate the mussel-inspired LBL design of advanced materials for environmental applications.

Attenuation of duck Tembusu virus ZJSBL01 strain following serial passage in BHK-21 cells supplied with 5-Fluorouracil.

Duck Tembusu virus (DTMUV) is a new pathogen that produces an acute and potent disease in ducks which has caused serious economic losses in China. In this study, a virulent strain of DTMUV, designated as ZJSBL01, was attenuated by serial passages in BHK-21 cells supplied with 5-Fluorouracil (5-FU) for 50 passages to induce mutation and attenuation. Growth kinetics of different passages of ZJSBL01 strain in BHK-21 cells show that these viruses have similar replication characteristics. The virus was highly attenuated after 40 passages in BHK-21 cells supplied with 5-FU, based on mortality, morbidity, and viral load in inoculated Sheldrake ducklings. In addition, all of the ducklings immunized with ZJSBL01-P40, the virus obtained at passage 40 of ZJSBL01, showed seroconversion on day 14 post inoculation. Moreover, P40 did not cause clinical symptom for layding ducks. Immunization with ZJSBL01-P40 could provide effective protection against the virulent parental ZJSBL01 strain. Seventeen amino acid substitutions were observed in the polyprotein of ZJSBL01-P40 compared with parental ZJSBL01. These results indicate that ZJSBL01-P40 may be a live vaccine candidate for prevention of DTMUV-disease.

Epidemiological investigation of fowl adenovirus infections in poultry in China during 2015-2018.

BACKGROUND: Fowl adenoviruses (FAdVs) are associated with many diseases, resulting in huge economic losses to the poultry industry worldwide. Since 2015, outbreaks of FAdV infections with high mortality rates have been reported in China. A continued surveillance of FAdVs contributes to understand the epidemiology of the viruses. RESULTS: We isolated 155 FAdV strains from diseased chickens from poultry in China between 2015 and 2018. PCR analysis determined that 123 samples were FAdV species C, 27 were FAdV species E, and five contained two different FAdV strains. The phylogenetic analysis demonstrates that these sequences of hexon regions were clustered into three distinct serotypes: FAdV-4 (79.4%, 123/155), FAdV-8a (13.5%, 21/155) and FAdV-8b (3.9%, 6/155), of which FAdV-4 was the dominant serotype in China. CONCLUSIONS: The characterization of newly prevalent FAdV strains provides valuable information for the development of an effective control strategy for FAdV infections in chickens.

Human papillomavirus DNA in surgical smoke during cervical loop electrosurgical excision procedures and its impact on the surgeon.

Objective: The purpose of this study was to explore whether human papillomavirus (HPV) DNA is present in surgical smoke generated by loop electrosurgical excision procedures (LEEPs). Furthermore, we investigated the impact of this HPV DNA on surgeons. Methods: A total of 134 outpatients with persistent HPV infections treated with LEEP for cervical intraepithelial neoplasia between 2015 and 2016, along with the corresponding LEEP operators, were included. The flow fluorescence in situ hybridization technique was used to detect HPV DNA in exfoliated cervical cells from the patients, in surgical smoke and in nasal epithelial cells from the surgeons before and after LEEP. Results: The positive rates of HPV DNA in the three types of samples mentioned above were 94.8%, 29.9% and 1.5%, respectively. The distribution of HPV subtypes in surgical smoke was identical to that in the cervical specimens. The positive rate of HPV DNA in surgical smoke was significantly increased for greater distances of the suction device from the surgical site. The nasal epithelial cells of two surgeons were positive for HPV DNA, and the genotypes were consistent with those in the corresponding surgical smoke. After a 3-6-month follow-up, the nasal swabs from these two doctors tested negative for HPV DNA. Conclusions: This study demonstrated the presence of HPV DNA in surgical smoke produced by LEEP and the risk of airborne transmission of HPV DNA during the operation. Fortunately, the HPV DNA in the nasopharynx of the operators was not persistent.

Recombinant fiber-2 protein protects Muscovy ducks against duck adenovirus 3 (DAdV-3).

As a novel duck adenovirus 3 (DAdV-3) infection caused significant economic losses to the poultry industry in China, there is an urgent need to develop a safe and effective vaccine. In the research, fiber-1 and fiber-2 proteins were expressed and purified, respectively. To evaluate the immunogenicity of the two recombinant proteins, we investigated the IgY antibodies and virus-neutralizing antibodies in duck sera. The protective efficacy was evaluated by mortality, virus shedding and histopathological examinations after challenged with the DAdV-3. Results showed that the IgY antibody levels of the fiber-2 group was significantly higher than that of the fiber-1 group and inactivated vaccine group. Ducks vaccinated with fiber-2 group provided full protection with no mortality, no virus shedding and no histological lesions, superior to other groups. These results suggest that the fiber-2 protein can be an ideal candidate for subunit vaccine against the disease.

Immunogenicity and protective efficacy of recombinant fiber-2 protein in protecting SPF chickens against fowl adenovirus 4.

Since a novel hyper-virulent fowl adenovirus serotype 4 (FAdV-4) infection occurred in 2015, the novel FAdV-4 has been widely spreading across China, causing significant economic losses to the poultry industry. As the urgency of the issue calls for effective and efficient solutions, the present study investigated the possibility of the fiber-2 protein of the FAdV-4 to serve as a vaccine candidate against the novel FAdV-4. In the research, fiber-2 proteins were expressed in Escherichia coli, and then purified. To evaluate the immunogenicity of the recombinant fiber-2 protein, we investigated both the humoral and cellular immune responses in chickens immunized with fiber-2. The humoral immunity was assessed by detecting IgY antibodies and virus-neutralizing antibodies in chicken serum at 7, 14, 21 days post-immunization (dpi). We examined cellular immune responses by detecting CD3+CD4+ and CD3+CD8+ changes in chickens' peripheral blood through using flow cytometry at 7, 14, 21 dpi. The cytokine production in the serum of the immunized chickens was detected by ELISA at 7, 14, 21 dpi to further explore the impact of the recombinant protein on the regulation of cytokines. The protective efficacy was determined by the survival rate of the immunized chickens challenged with the novel FAdV-4. The results show that the level of IgY antibodies of the chickens immunized with fiber-2 protein was significantly higher than that of the chickens immunized with an inactivated vaccine against FAdV-4. Moreover, 7 days after immunization, the CD4+ T-cell proliferative response of the chickens immunized with fiber-2 was significantly higher than that of the chickens immunized with the inactivated vaccine. Challenge experiment showed that the fiber-2 protein could provide full protection and the inactivated vaccine could provide 90 percent protection against the FAdV-4. These results suggest that the recombinant fiber-2 protein can be an ideal candidate for subunit vaccines against the disease.

Brucella abortus phosphoglyceromutase and dihydrodipicolinate reductase induce Th1 and Th2-related immune responses.

Brucellae are intracellular bacterial pathogens that cause Brucellosis, bringing great economic burdens to developing countries. The pathogenic mechanisms of Brucella are still poorly understood. Earlier immune response plays an important role in the Brucella infection. Phosphoglyceromutase (PGM) and dihydrodipicolinate reductase (DapB) were cloned, expressed, purified, and their immunocompetence was analyzed. Cytokines were detected by murine macrophages (RAW 264.7) and splenocytes that stimulated with the two recombinant proteins. The immune responses were analyzed by ELISA from mice with the two recombinant proteins immunized. TNF-α, IL-6 and IL-8 were produced in stimulated RAW 264.7 cells and splenocytes. Th1-type cytokines, IFN-γ and IL-2, induced in RAW 264.7 cells and splenocytes were higher then Th2-type cytokines, IL-4 and IL-5. Th2-related immune response was induced in splenocytes obtained 35 days after mice immunized with the two proteins. The production of IgG1 was higher than IgG2a in immunized mice. Taken together, our results demonstrated that the two proteins could induce Th1 and Th2-type immune responses in vivo and in vitro.

Linking expression of aquaporin 3 to activation of JNK pathway.

Aquaporin 3 (AQP3) has been shown to be low in the amnion and chorion tissues of patients with oligohydramnios and that S. miltiorrhiza, a Chinese herbal medicine, results in increased AQP3 in human amniotic epithelial cells (hAECs). Here, we provide evidence for the involvement of the JNK pathway in AQP3 regulation in isolated oligohydramnios tissues in vitro, in hAECs derived from normal amniotic fluid and fluid from patients with isolated oligohydramnios. Phosphorylation of JNK was suppressed by pretreatment of cells with JNK-specific inhibitor (SP600125) and was up-regulated by S. miltiorrhiza; S. miltiorrhiza combined with SP600125 prevented SP600125-induced down-regulation of phospho-JNK both in normal amniotic fluid volume and in isolated oligohydramnios. In isolated oligohydramnios, AQP3 expression was significantly suppressed by SP600125 in a concentration- and time-dependent mannner, while its expression was up-regulated by S. miltiorrhiza. S. miltiorrhiza combined with SP600125 inhibited the increased expression of AQP3 relative to the S. miltiorrhiza treated group. Together, the data suggest that c-jun N-terminal kinase (JNK) pathway unerlies the regulation of AQP3 by S. miltiorrhiza amnion and chorion tissues.