PCV2 Induced Endothelial Derived IL-8 Affects MoDCs Maturation Mainly via NF-κB Signaling Pathway.

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8.

Boosting the Luminescence of a Europium(III)-ß-Diketonate Complex-Nanoclay Aqueous Solution by Acetylcholine.

It is a challenging task to prepare lanthanide complex-based luminescent materials with high quantum efficiency in aqueous solution, since the excited state of Ln3+ can be significantly quenched by water through the excitation of the O-H vibrations. Herein, we present a simple and environmentally friendly strategy to prepare strongly red-light-emitting lanthanide complex-based luminescent materials by loading 2-thenoyltrifluoroacetate (TTA) on the Eu3+-exchanged nanoclay (Eu3+(TTAn)-NC, NC = nanoclay) and coadsorption of choline chloride (ChCl) or acetylcholine chloride (AChCl) in water. The coadsorbed molecules remarkably boosted the luminescence of Eu3+(TTAn)-NC, which is tentatively ascribed to the removal of waters coordinated in the Eu3+ coordination sphere via the complete coordination of TTA mediated by ChCl or AChCl. Highly luminescent films were facilely prepared by mixing a Eu3+(TTAn)-NC aqueous solution with PVA-ChCl (PVA-AChCl) deep eutectic solvents. This work provides a simple and environmentally friendly way for preparing highly luminescent emitting luminescent materials in aqueous solution.

Spidroin-mimetic Engineered Protein Fibers with High Toughness and Minimized Batch-to-batch Variations through ß-sheets Co-assembly.

Synthetic spidroin fibers have not yet attained the same level of toughness and stability as natural spider silks due to the complexity of composition and hierarchical structure. Particularly, understanding the intricate interactions between spidroin components in spider fiber is still elusive. Herein, we report modular design and preparation of spidroin-mimetic fibers composed of a conservative C-terminus spidroin module, two different natural ß-sheets modules, and a non-spidroin random-coil module. The resulting fibers exhibit a toughness of ~200 MJ/m3, reaching the highest value among the reported artificial spider silks. The interactions between two components of recombinant spidroins facilitate the intermolecular co-assembly of ß-sheets, thereby enhancing the mechanical strength and reducing batch-to-batch variability in the dual-component spidroin fibers. Additionally, the dual-component spidroin fibers offer potential applications in implantable or even edible devices. Therefore, our work presents a generic strategy to develop high-performance protein fibers for diverse translations in different scenarios.

Comprehensive Analysis Reveals the Potential Roles of CDKN3 in Pancancer and Verification in Endometrial Cancer.

Background: Cyclin-dependent kinase inhibitor 3 (CDKN3) has been studied in many cancers. However, the comprehensive and systematic pancancer analysis of CDKN3 genes is still lacking. Methods: Data were downloaded from online databases. R was used for analysis of the differential expression and gene alteration of CDKN3 and of the associations between CDKN3 expression and survival, signaling pathways, and drug sensitivity. Clinical samples and in vitro experiments were selected for verification. Results: CDKN3 expression was higher in most types of cancers, and this phenotype was significantly correlated with poor survival. CDKN3 showed gene alterations and copy number alterations in many cancers and associated with some immune-related pathways and factors. Drug sensitivity analysis elucidated that CDKN3 could be a useful marker for therapy selection. Clinical samples elucidated CDKN3 expressed high in endometrial cancer tissue. In vitro studies showed that CDKN3 induced pro-tumor effect in immune environment and facilitated endometrial cancer cell proliferation and G1/S phase transition. Conclusion: CDKN3 has been shown to be highly expressed in most types of cancers and promoted cancer cell progression. CDKN3 may serve as a novel marker in clinical diagnosis, treatment, and prognosis prediction in future.

Stable and Highly Luminescent Silver Nanoclusters in the 13X Zeolite Enabled by Mg2+ Doping and Their Luminescence Tuning by Heating Temperature.

Zeolite-confined silver nanoclusters (Ag-zeolite) have aroused vast interest due to their remarkable luminescence. The countercations within a zeolite play critical roles in determining the luminescent properties of the resulting Ag-zeolite. We observed, in this work, that introducing Mg2+ enabled the Ag-13X zeolite a stable and bright yellow emission with a high PLQY of 94.6%, the first report on the luminescence enhancement of the Ag-13X zeolite by Mg2+, to the best of our knowledge. The formation of specific internal electric fields inside 13X and the structural contraction of the zeolite framework due to the high charge density and the small ionic radius of Mg2+ are believed to be responsible for the enhanced stable and bright yellow emission. The stabilization effect of Mg2+ is removed by increasing the heating temperature above 700 °C, which leads to the variation of silver nanoclusters as a result of the framework collapse of the zeolite. The Ag-zeolite synthesized by us, featured with a broad emission band, a high PLQY of 94.6%, and good thermal stability, can be considered a suitable candidate to replace the traditional commercial yellow-emitting phosphor YAG:Ce3+ for light-based applications. This work contributes to a valuable reference for the rational design of silver nanoclusters confined in zeolites with promising new functionalities and stimulates potential applications as novel phosphors for near-ultraviolet light-emitting diodes (NUV-LEDs).

High-Quantum-Efficiency Blue Phosphors with Superior Thermal Stability Derived from Eu3+-Doped Faujasite Y Zeolite.

Blue phosphors of high efficiency and superior thermal stability constitute the critical component for achieving high-quality white light-emitting diodes (WLEDs). Herein, we report a highly efficient blue-emitting phosphor with superior thermal stability by heating Eu3+-doped Faujasite Y zeolite under a reducing atmosphere. The intensity and peak value of the phosphor are highly dependent on calcination temperature, and the intensity of PLE and PL spectra reaches a maximum at 1100 °C. Under the excitation of 360 nm, the phosphor shows a high quantum efficiency (90%) and thermal stability (the emission intensity at 423 K is about 125% of that at room temperature). WLEDs fabricated using this blue phosphor, a yellow Eu2+-SOD phosphor, and a commercially available red Sr2Si5N8:Eu2+ phosphor exhibit an excellent optical performance with a correlated color temperature of 4359 K and a color rendering index of 97. This work provides a new strategy for the synthesis of phosphors with high thermal stability and luminous efficiency.

Fluorescence turn-on mode of Eu3+ complex nanocomposite to detect histamine for seafood freshness.

Biogenic amines (BAs), which naturally occur as chemicals in seafood, are indicators of food freshness and quality. High concentrations of BAs can cause an undesirable inflammatory response. However, traditional detection methods cannot meet the needs of rapid analysis nowadays. It is essential to explore a simple and valid method to monitor the food quality. Herein, we design and prepare a nanoclay-based turn on fluorescent material with BAs response, which could be used for the real-time and visual detection of raw fish freshness. As the concentration of BAs increase, the sensor of the fluorescence signal is significantly enhanced. The sensor demonstrated wonderful response and sensitivity which showed a detection limit of 0.935 mg/L for typical BAs histamine within a linear range of 2-14 mg/L in an aqueous solution. More importantly, we developed a responsive BAs device by doping the sensor into polyvinyl alcohol (PVA), which is well applied as a rapid-responsive fluorescent marker for visual monitoring the freshness of raw fish.

Porcine Circovirus 2 Increases the Frequency of Transforming Growth Factor-ß via the C35, S36 and V39 Amino Acids of the ORF4.

Porcine circovirus 2 (PCV2) is one of the most important endemic swine pathogens, inducing immunosuppression in pigs and predisposing them to secondary bacterial or viral infections. Our previous studies show that PCV2 infection stimulated pig intestinal epithelial cells (IPEC-J2) to produce the secretory transforming growth factor-ß (TGF-ß), which, in turn, caused CD4+ T cells to differentiate into regulatory T cells (Tregs). This may be one of the key mechanisms by which PCV2 induces immunosuppression. Here, we attempt to identify the viral proteins that affect the TGF-ß secretion, as well as the key amino acids that are primarily responsible for this occurrence. The three amino acids C35, S36 and V39 of the ORF4 protein are the key sites at which PCV2 induces a large amount of TGF-ß production in IPEC-J2 and influences the frequency of Tregs. This may elucidate the regulatory effect of PCV2 on the Tregs differentiation from the perspective of virus structure and intestinal epithelial cell interaction, laying a theoretical foundation for improving the molecular mechanism of PCV2-induced intestinal mucosal immunosuppression in piglets.

Construction of a Triple-Gene Deletion Mutant of Orf Virus and Evaluation of Its Safety, Immunogenicity and Protective Efficacy.

Contagious ecthyma is a zoonotic disease caused by the orf virus (ORFV). Since there is no specific therapeutic drug available, vaccine immunization is the main tool to prevent and control the disease. Previously, we have reported the construction of a double-gene deletion mutant of ORFV (rGS14ΔCBPΔGIF) and evaluated it as a vaccine candidate. Building on this previous work, the current study reports the construction of a new vaccine candidate, generated by deleting a third gene (gene 121) to generate ORFV rGS14ΔCBPΔGIFΔ121. The in vitro growth characteristics, as well as the in vivo safety, immunogenicity, and protective efficacy, were evaluated. RESULTS: There was a minor difference in viral replication and proliferation between ORFV rGS14ΔCBPΔGIFΔ121 and the other two strains. ORFV rGS14ΔCBPΔGIFΔ121 induced continuous differentiation of PBMC to CD4+T cells, CD8+T cells and CD80+CD86+ cells and caused mainly Th1-like cell-mediated immunity. By comparing the triple-gene deletion mutant with the parental strain and the double-gene deletion mutant, we found that the safety of both the triple-gene deletion mutant and the double-gene deletion mutant could reach 100% in goats, while the safety of parental virus was only 50% after continually observing immunized animals for 14 days. A virulent field strain of ORFV from an ORF scab was used in the challenge experiment by inoculating the virus to the hairless area of the inner thigh of immunized animals. The result showed that the immune protection rate of triple-gene deletion mutant, double-gene mutant, and the parental virus was 100%, 66.7%, and 28.6%, respectively. In conclusion, the safety, immunogenicity, and immune-protectivity of the triple-gene deletion mutant were greatly improved to 100%, making it an excellent vaccine candidate.

Clusterization-Triggered Room Temperature Phosphorescence Supramolecular Assembly with Extraordinary Stimulus-responsive Features from Nonaromatic Amino Acids.

Achieving stimulus-responsive performance in room-temperature phosphorescence (RTP) materials especially systems without classic conjugated groups is attractive and important but remains a great challenge. Herein we propose a universal approach to construct colors-tunable RTP supramolecular co-assemblies (AC@amino acid) with excitation wavelength-dependent properties through co-assembly of functional aminoclay (AC) and nonconjugated amino acid using environmentally friendly strategy. Experimental and theoretical results successfully disclose that the RTP feature is attributable to space conjugation through effective space electronic communications among different π and n (lone pair) electrons of amino acid molecules and the effective stabilization of their triplet state by AC. Meanwhile, their colors-tunable performances are mainly owing to the co-existence of clusters with different aggregates degree through recrystallization of amino acid taking AC as a template. Importantly, AC@amino acid exhibit sensitive stimulus response features towards water, yet their RTP performance can be maintained in other solvents, such as ethanol (EtOH). By virtue of this unique feature, multilevel information encryption application were demonstrated. This work provides a unique insight and more deep understanding on designing novel RTP systems without classic conjugated groups. Importantly, their extraordinary stimulus-responsive performances endow these RTP systems with a highly promising potential for intelligent information encryption applications.

Maternal Infection with Listeria monocytogenes in Twin Pregnancy.

Listeria monocytogenes is the conditional pathogenic bacteria, and pregnant women are at higher risk of infection due to depressed immunity. Infection with Listeria monocytogenes in twin pregnancy is rare but devastating, which puts forwards a great challenge for clinical management. Here, a 24-year-old woman was diagnosed with twin pregnancy, intrauterine death of one fetus and fever at 29+4 week of gestation. Two days later, she developed into pericardial effusion, pneumonedema and potential septic shock. The emergent cesarean delivery was performed after anti-shock treatment. One alive and another dead fetus were delivered. Then, she developed postpartum hemorrhage after the surgery. Urgent exploratory laparotomy was conducted at the sites of cesarean section and B-Lynch suture to stop bleeding. The culture of blood and maternal side of both placentas indicated Listeria monocytogenes. Following anti-infection therapy with ampicillin-sulbactam, she recovered well and discharged with negative result of blood bacterial culture and normal inflammatory indicators. The patient was hospitalized for a total of 18 days including 2 days in the intensive care unit (ICU), and the anti-infection treatment was conducted throughout the course. Symptoms of the Listeria monocytogenes infection in pregnancy are non-specific, which should be paid more attention in case of unexplained fever and fetal distress. The blood culture is effective for accurate diagnosis. Listeria monocytogenes infection is associated with poor pregnancy outcomes. Close monitoring of fetal condition, early intervention with antibiotics, timely termination of pregnancy and comprehensive management of complications are essential for better prognosis.

Room-Temperature Self-Healing Glassy Luminescent Hybrid Film.

The self-healing of glassy polymer materials on site has always been a huge challenge due to their frozen polymer network. We herein report self-repairable glassy luminescent film by assembling a lanthanide-containing polymer with randomly hyperbranched polymers possessing multiple hydrogen (H) bonds. Because of multiple H bonds, the hybrid film exhibits enhanced mechanical strength, with high glass transition temperature (Tg) of 40.3 °C and high storage modulus of 3.52 GPa, meanwhile, dynamic exchange of multiple H bonds enables its rapid room-temperature self-healing ability. This research provides new insights in preparing mechanical robust yet repairable polymeric functional materials.

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women.

Introduction: Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. Methods: This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. Results: The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). Discussion: The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.

Interactions between microbiota and cervical epithelial, immune, and mucus barrier.

The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.

Amide-Directed, Rhodium-Catalyzed Enantioselective Hydrosilylation of Unactivated Internal Alkenes.

Despite the recent advances made in the area of asymmetric hydrosilylation, metal-catalyzed enantioselective hydrosilylation of unactivated internal alkenes remains a challenge. Here, we report a rhodium-catalyzed enantioselective hydrosilylation of unactivated internal alkenes bearing a polar group. The coordination assistance by an amide group enables the hydrosilylation to occur with high regio- and enantioselectivity.

Glucose metabolic reprogramming and its therapeutic potential in obesity-associated endometrial cancer.

Endometrial cancer (EC) is a common gynecological cancer that endangers women health. Although substantial progresses of EC management have been achieved in recent years, the incidence of EC still remains high. Obesity has been a common phenomenon worldwide that increases the risk of EC. However, the mechanism associating obesity and EC has not been fully understood. Metabolic reprogramming as a remarkable characteristic of EC is currently emerging. As the primary factor of metabolic syndrome, obesity promotes insulin resistance, hyperinsulinemia and hyperglycaemia. This metabolic disorder remodels systemic status, which increases EC risk and is related with poor prognosis. Glucose metabolism in EC cells is complex and mediated by glycolysis and mitochondria to ensure energy requirement. Factors that affect glucose metabolism may have an impact on EC initiation and progression. In this study, we review the glucose metabolic reprogramming of EC not only systemic metabolism but also inherent tumor cell metabolism. In particular, the role of glucose metabolic regulation in malignant properties of EC will be focused. Understanding of metabolic profile and glucose metabolism-associated regulation mechanism in EC may provide novel perspective for treatment.

A rapid self-healing glassy polymer/metal-organic-framework hybrid membrane at room temperature.

The development of repairable MOF-polymer hybrid materials will greatly extend their service life by repairing fractured parts on the spot; however, it is difficult for robust glassy polymers to self-heal below the glass transition temperature (Tg) as the polymer network is frozen. We herein report glassy polyMOF-RHP hybrid membranes by integrating lanthanide polyMOF (polyLnMOF) with randomly hyperbranched polymers (RHP) bearing a high density of hydrogen bonds. Since crystalline lanthanide MOFs act as multiconnected cross-linking agents and cross-link the interpenetrating polymer network, the obtained polyLnMOF-polymer membrane shows enhanced mechanical strength with a storage modulus of 3.09 GPa and a Tg up to 49 °C. Meanwhile, the high intersegment migration ability of the polyLnMOF-polymer network facilitates the exchange of hydrogen-bonded pairs even in the glassy state, leading to an instantaneous room-temperature self-healing ability. The polyLnMOF-polymer membranes inherit the ratiometric temperature-sensing behavior of pristine lanthanide MOFs, resulting in more processable temperature-sensing membranes. This work provides an appealing strategy for the design of mechanically robust, yet self-healing, MOF-polymer functional materials.

Leveraging 16S rRNA data to uncover vaginal microbial signatures in women with cervical cancer.

Microbiota-relevant signatures have been investigated for human papillomavirus-related cervical cancer (CC), but lack consistency because of study- and methodology-derived heterogeneities. Here, four publicly available 16S rRNA datasets including 171 vaginal samples (51 CC versus 120 healthy controls) were analyzed to characterize reproducible CC-associated microbial signatures. We employed a recently published clustering approach called VAginaL community state typE Nearest CentroId clAssifier to assign the metadata to 13 community state types (CSTs) in our study. Nine subCSTs were identified. A random forest model (RFM) classifier was constructed to identify 33 optimal genus-based and 94 species-based signatures. Confounder analysis revealed confounding effects on both study- and hypervariable region-associated aspects. After adjusting for confounders, multivariate analysis identified 14 significantly changed taxa in CC versus the controls (P < 0.05). Furthermore, predicted functional analysis revealed significantly upregulated pathways relevant to the altered vaginal microbiota in CC. Cofactor, carrier, and vitamin biosynthesis were significantly enriched in CC, followed by fatty acid and lipid biosynthesis, and fermentation of short-chain fatty acids. Genus-based contributors to the differential functional abundances were also displayed. Overall, this integrative study identified reproducible and generalizable signatures in CC, suggesting the causal role of specific taxa in CC pathogenesis.

Tunable Luminescence of Silver Nanoclusters Confined in SOD/FAU Zeolites and Selective Sensing for Organic Amine.

A series of Ag-zeolite luminescent composites are prepared based on SOD and FAUY zeolites, and the effect of zeolite host particle size on their dynamic luminescent emission properties was discussed for the first time. The relationship between zeolite particle size and the nucleation of silver nanoclusters (AgNCs) is revealed. With the increase of zeolite particle size from nanometers to microns, the luminescent color of both Ag-SOD and Ag-Y composites shows significant blue shift. The observed tunable luminescence can be accounted for the slower nucleation rate of AgNCs in micron-scale zeolites with longer channels, resulting in smaller nuclearity of AgNCs within large-size zeolites, through the characterization of extended X-ray absorption fine structure, implying the important roles played by the zeolite themselves in determining the luminescence properties. Moreover, the composites prepared by us feature simple signal transduction, fast response (30 s), and excellent selectivity and sensitivity for discriminative luminescence detection of triethylamine and ethylamine, and they have good reversible luminescence response after sensing HAc gas, which might imply the potential applications in the volatile organic amine detection and information encryption field.

The roles and clinical applications of interleukins in endometrial carcinoma.

As a common malignant tumor of the female reproductive system, endometrial carcinoma (EC) seriously endangers women's health with an increasing incidence. The oncogenesis and progression of cancer are closely linked with immune microenvironment, of which interleukins are the important components. In order to illustrate the roles and clinical applications of interleukins in EC, literature of interleukins and EC were reviewed. Based on the present studies, interleukins play crucial roles in the oncogenesis and development of EC via regulating the proliferation, migration, invasion, angiogenesis, apoptosis, pyroptosis and autophagy of EC as well as the immune function against EC. And some of the interleukins seems to have prospective clinical applications in EC, such as evaluating the risk of tumorigenesis, discriminating the malignancy from benign disorders or normal condition, indicating cancer aggressiveness, predicting the prognosis of patients and serving as the novel therapy. However, there is still a long way to go before the clinical applications of interleukins in EC come into reality. Nevertheless, it is certain that the exploration of interleukins will definitely be of great benefit to the screening, diagnosis and treatment of EC in the future.