Electron diffraction of foam-like clusters between xenon and helium in superfluid helium droplets.

We report electron diffraction results of xenon clusters formed in superfluid helium droplets, with droplet sizes in the range of 105-106 atoms/droplet and xenon clusters from a few to a few hundred atoms. Under four different experimental conditions, the diffraction profiles can be fitted using four atom pairs of Xe. For the two experiments performed with higher helium contributions, the fittings with one pair of Xe-He and three pairs of Xe-Xe distances are statistically preferred compared with four pairs of Xe-Xe distances, while the other two experiments exhibit the opposite preference. In addition to the shortest pair distances corresponding to the van der Waals distances of Xe-He and Xe-Xe, the longer distances are in the range of the different arrangements of Xe-He-Xe and Xe-He-He-Xe. The number of independent atom pairs is too many for the small xenon clusters and too few for the large clusters. We consider these results evidence of xenon foam structures, with helium atoms stuck between Xe atoms. This possibility is confirmed by helium time-dependent density functional calculations. When the impact parameter of the second xenon atom is a few Angstroms or longer, the second xenon atom fails to penetrate the solvation shell of the first atom, resulting in a dimer with a few He atoms in between the two Xe atoms. In addition, our results for larger droplets point toward a multi-center growth process of dopant atoms or molecules, which is in agreement with previous proposals from theoretical calculations and experimental results.

Comparison of different doses of Tripterygium glycosides treating in IgA vasculitis nephritis: A Bayesian network meta-analysis.

Background: Tripterygium glycosides (TG) is extracted from the roots of Tripterygium wilfordii Hook F (Lei gong teng, a traditional Chinese medicine). It is widely used in China to treat immunoglobulin A vasculitis nephritis (IgAVN), which is a common secondary glomerular disease. As there are no guidelines for the rational application of TG, we performed this study to evaluate the efficacy and safety of different doses of TG and to determine the optimal treatment for IgAVN. Methods: Ten databases were searched from their inception to April 2023 for randomised controlled trials (RCTs) using TG, TG combined with glucocorticoids (GC), or TG combined with traditional Chinese medicine (TCM) to treat IgAVN. A network meta-analysis was performed following the protocol (CRD42023401645). Results: Forty-four eligible RCTs involving 3402 patients were included. For effective rate, TG 1.5 mg/kg/d (TG1.5) + TCM was ranked as the best intervention, followed by TG 1.0 mg/kg/d (TG1.0) + TCM, TG1.5, TG1.0+GC, TG1.0, TCM, GC, and routine treatment (RT). TG1.0+TCM ranked best in reducing recurrence, followed by TG1.0+GC, GC, TG1.5, and RT. Compared with TG1.0, TG1.0+TCM and TG1.5+TCM effectively reduced liver injury events. Compared with TG1.5, TG1.5+TCM and TG1.0+TCM effectively reduced leukopenia events. No significant differences in the reduction of gastrointestinal events were observed between the interventions. Subgroup analyses explored the effects of the participants' age. The intervention rankings of the outcomes generally remained consistent. Only a small difference was observed in gastrointestinal events. TCM was the best treatment for reducing gastrointestinal events in paediatric patients. Conclusions: The results showed a positive correlation between dose and efficacy, whereas no relationship was found between dose and adverse events. TCM can boost the efficacy and reduce adverse events when combined with TG. In conclusion, we consider TG1.5+TCM as the best treatment for IgAVN. However, further research is required to confirm these findings.

Heterologous Prime-Boost Immunization Strategies Using Varicella-Zoster Virus gE mRNA Vaccine and Adjuvanted Protein Subunit Vaccine Triggered Superior Cell Immune Response in Middle-Aged Mice.

Purpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response. Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared. Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation. Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.

Flt3 ligand augments immune responses to soluble PD1-based DNA vaccine via expansion of type 1 conventional DCs.

DNA vaccines are prospective for their efficient manufacturing process, but their immunogenicity is limited as they cannot efficiently induce CD8+ T cell responses. A promising approach is to induce cross-presentation by targeting antigens to DCs. Flt3L can expand the number of type 1 conventional DCs and thereby improve cross-presentation. In this study, we first constructed a DNA vaccine expressing soluble PD1 and found that the therapeutic effect of targeting DCs with only the sPD1 vaccine was limited. When combined the vaccine with Flt3L, the anti-tumor effect was significantly enhanced. Considering the complexity of tumors and that a single method may not be able to activate a large number of effective CD8+ T cells, we combined different drugs and the vaccine with Flt3L based on the characteristics of different tumors. In 4T1 model, we reduced Tregs through cyclophosphamide. In Panc02 model, we increased activated DCs by using aCD40. Both strategies triggered strong CD8+ T cell responses and significantly improved the therapeutic effect. Our study provides important support for the clinical exploration of DC-targeted DNA vaccines in combination with Flt3L.

Anterior percutaneous full-endoscopic transcorporeal decompression for cervical disc herniation: a finite element analysis and long-term follow-up study.

OBJECTIVE: The purpose of this study was to investigate the long-term consequences on the cervical spine after Anterior transcorporeal percutaneous endoscopy cervical discectomy (ATc-PECD) from the biomechanical standpoint. METHODS: A three-dimensional model of the normal cervical spine C2-T1 was established using finite element method. Subsequently, a disc degeneration model and degeneration with surgery model were constructed on the basis of the normal model. The same loading conditions were applied to simulate flexion, extension, lateral bending and axial rotation of the cervical spine. We calculated the cervical range of motion (ROM), intradiscal pressure, and intravertebral body pressure under different motions for observing changes in cervical spine biomechanics after surgery. At the same time, we combined the results of a long-term follow-up of the ATc-PECD, and used imaging methods to measure vertebral and disc height and cervical mobility, the Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to assess pain relief and neurological functional recovery. RESULTS: The long-term follow-up results revealed that preoperative JOA score, neck VAS score, hand VAS score, IDH, VBH, and ROM for patients were 9.49 ± 2.16, 6.34 ± 1.68, 5.14 ± 1.48, 5.95 ± 0.22 mm, 15.41 ± 1.68 mm, and 52.46 ± 9.36° respectively. It changed to 15.71 ± 1.13 (P < 0.05), 1.02 ± 0.82 (P < 0.05), 0.77 ± 0.76 (P < 0.05), 4.73 ± 0.26 mm (P < 0.05), 13.67 ± 1.48 mm (P < 0.05), and 59.26 ± 6.72° (P < 0.05), respectively, at 6 years postoperatively. Finite element analysis showed that after establishing the cervical spondylosis model, the overall motion range for flexion, extension, lateral bending, and rotation decreased by 3.298°, 0.753°, 3.852°, and 1.131° respectively. Conversely, after establishing the bone tunnel model, the motion range for these actions increased by 0.843°, 0.65°, 0.278°, and 0.488° respectively, consistent with the follow-up results. Moreover, analysis of segmental motion changes revealed that the increased cervical spine mobility was primarily contributed by the surgical model segments. Additionally, the finite element model demonstrated that bone tunneling could lead to increased stress within the vertebral bodies and intervertebral discs of the surgical segments. CONCLUSIONS: Long-term follow-up studies have shown that ATc-PECD has good clinical efficacy and that ATc-PECD can be used as a complementary method for CDH treatment. The FEM demonstrated that ATc-PECD can lead to increased internal stresses in the vertebral body and intervertebral discs of the operated segments, which is directly related to cervical spine degeneration after ATc-PECD.

A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer's disease in 3xTg mice.

Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aß-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aß and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aß and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aß and pTau in 3xTg transgenic mice. It significantly eradicated Aß plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aß and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.

Conceptualizing vaccine champions from an implementation science perspective: Findings from a national survey of primary care health professionals.

OBJECTIVE: Clinical champions are healthcare professionals who help their colleagues improve the delivery of evidence-based care. Because little is known about champions working in the context of adolescent vaccination, we sought to identify vaccine champion roles among primary care health professionals (PCHPs). METHODS: In 2022, we surveyed 2527 US PCHPs who serve adolescents. The survey assessed the extent to which respondents identified as vaccine champions and the activities they performed. Guided by the Consolidated Framework for Implementation Research, we used these data to categorize PCHPs as: champions who led projects to increase vaccination rates ("implementation leaders"); facilitating champions who more generally shared vaccination data, information, and encouragement ("facilitators"); or non-champions. We used multinomial logistic regression to identify correlates of being a leader or facilitator as opposed to a non-champion. RESULTS: About one-fifth (21%) of PCHPs were implementation leaders, one-quarter (25%) were facilitators, and the remainder (54%) were non-champions. Leaders were more common among PCHPs with medium or high versus low practice experience (31% and 36% versus 20%, both p < .01) and adolescent patient volume (29% and 39% versus 17%, both p < .01). Being a facilitator was also associated with higher practice experience and patient volume. Leaders and facilitators reported a similar number of barriers to their work (mean = 1.8 and 1.9, respectively), with time and competing quality metrics being most common. CONCLUSIONS: Our findings suggest that both implementation leaders and facilitators are common vaccine champions in adolescent primary care. These champions are more often found among PCHPs with higher experience and patient volume.

Structure, anti-inflammatory and anti-bacterial activities of novel pentacyclic triterpenoids and other constituents from the leaves of Pittosporum elevaticostatum.

The investigation of the leaves of Pittosporum elevaticostatum Chang et Yan led to the isolation of fifteen pentacyclic triterpenoids (1-15), including five previously undescribed ones (1-5), and nine others (16-24). The structures of compounds 1-5 were elucidated based on comprehensive spectroscopic techniques, including one dimension (1D) and 2D nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and other methods. Compounds 2 and 13 demonstrated significant inhibitory activity against Listeria monocytogenes (L. monocytogenes) with minimum inhibitory concentration (MIC) values of 32 µM. Scanning electron microscopy (SEM) observations revealed insights into the antibacterial mechanism, indicating that compounds 2 and 13 either prevent biofilm formation of dispersed the preformed cell membranes. Additionally, compounds 1, 5, 7, and 12 exhibited anti-inflammatory activity on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells with IC50 values ranging from 11.27 to 17.80 µM.

Quercetin-Loaded Zeolitic Imidazolate Framework-8 (ZIF-8) Nanoparticles Attenuate Osteoarthritis by Activating Autophagy via the Pi3k/Akt Signaling.

Osteoarthritis treatment remains a significant clinical challenge. Quercetin, a natural flavonoid with anti-inflammatory and antiapoptotic properties, might be utilized to treat OA. However, poor water solubility and short joint retention duration limit its bioavailability and translation to clinical applications. A one-step self-assembly method was utilized to fabricate quercetin-loaded zeolitic imidazolate framework-8 (Qu@ZIF-8) nanoparticles using zinc ions, 2-methylimidazole, and quercetin. In vitro tests showed that Qu@ZIF-8 nanoparticles released pH-responsive agents into chondrocytes, effectively protecting them from interleukin (IL)-induced inflammation and apoptosis, thereby promoting cartilage anabolic activities. These underlying mechanisms revealed a remarkable increase of autophagy in IL-ß-treated chondrocytes, followed by the inhibition of the Pi3k/Akt signaling pathway, which contributed to the protective effect of Qu @ZIF-8. By the establishment of medial meniscus instability (DMM) in OA mice, Qu@ZIF-8 substantially improved cartilage structural integrity and chondrocyte status, as well as attenuated OA progression. Importantly, Qu@ZIF-8 outperformed quercetin alone in the treatment of OA due to its control release. The combined research findings indicate that Qu@ZIF-8 shields chondrocytes from inflammation and apoptosis by activating autophagy and repressing the Pi3k/Akt pathway. This investigation may provide new insights for clinically extending the therapy of OA.

ECM Microenvironment in Vascular Homeostasis: New Targets for Atherosclerosis.

Alterations in vascular extracellular matrix (ECM) components, interactions, and mechanical properties influence both the formation and stability of atherosclerotic plaques. This review discusses the contribution of the ECM microenvironment in vascular homeostasis and remodeling in atherosclerosis, highlighting Cartilage oligomeric matrix protein (COMP) and its degrading enzyme ADAMTS7 as examples, and proposes potential avenues for future research aimed at identifying novel therapeutic targets for atherosclerosis based on the ECM microenvironment.

Volatiles emitted by Pseudomonas aurantiaca ST-TJ4 trigger systemic plant resistance to Verticillium dahliae.

Verticillium dahliae is among the most devastating fungal pathogens, causing significant economic harm to agriculture and forestry. To address this problem, researchers have focused on eliciting systemic resistance in host plants through utilizing volatile organic compounds (VOCs) produced by biological control agents. Herein, we meticulously measured the quantity of V. dahliae pathogens in plants via RTqPCR, as well as the levels of defensive enzymes and pathogenesis-related (PR) proteins within plants. Finally, the efficacy of VOCs in controlling Verticillium wilt in cotton was evaluated. Following treatment with Pseudomonas aurantiaca ST-TJ4, the expression of specific VdEF1-α genes in cotton decreased significantly. The incidence and disease indices also decreased following VOC treatment. In cotton, the salicylic acid (SA) signal was strongly activated 24 h posttreatment; then, hydrogen peroxide (H2O2) levels increased at 48 h, and peroxidase (POD) and catalase (CAT) activities increased to varying degrees at different time points. The malondialdehyde (MDA) content and electrolyte leakage in cotton treated with VOCs were lower than those in the control group, and the expression levels of chitinase (CHI) and PR genes (PR10 and PR17), increased at various time points under the ST-TJ4 treatment. The activity of phenylalanine ammonia lyase (PAL) enzymes in cotton treated with VOCs was approximately 1.26 times greater than that in control plants at 24 h，while the contents of phenols and flavonoids increased significantly in the later stage. Additionally, 2-undecanone and 1-nonanol can induce a response in plants that enhances disease resistance. Collectively, these findings strongly suggest that VOCs from ST-TJ4 act as elicitors of plant defence and are valuable natural products for controlling Verticillium wilt.

Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice.

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

Immunomodulatory molecules in colorectal cancer liver metastasis.

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths. According to clinical diagnosis and treatment, liver metastasis occurs in approximately 50 % of CRC patients, indicating a poor prognosis. The unique immune tolerance of the liver fosters an immunosuppressive tumor microenvironment (TME). In the context of tumors, numerous membrane and secreted proteins have been linked to tumor immune evasion as immunomodulatory molecules, but much remains unknown about how these proteins contribute to immune evasion in colorectal cancer liver metastasis (CRLM). This article reviews recently discovered membrane and secreted proteins with roles as both immunostimulatory and immunosuppressive molecules within the TME that influence immune evasion in CRC primary and metastatic lesions, particularly their mechanisms in promoting CRLM. This article also addresses screening strategies for identifying proteins involved in immune evasion in CRLM and provides insights into potential protein targets for treating CRLM.

Distribution and dynamic changes of Huanglongbing pathogen in its insect vector Diaphorina citri.

The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama is the leading vector of Candidatus Liberibacter asiaticus (CLas), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of CLas within ACP are critical to understanding how the transmission, spread and infection of CLas occurs within its host vector in nature. In this study, the distribution and titer changes of CLas in various tissues of ACP 5th instar nymphs and adults were examined by fluorescence in situ hybridization (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5th instar nymphs and adults were infected with CLas following feeding on infected plants, and that CLas had widespread distribution in most of the tissues of ACP. The titers of CLas within the midgut, salivary glands and hemolymph tissues were the highest in both 5th instar nymphs and adults. When compared with adults, the titers of CLas in these three tissues of 5th instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of CLas demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of CLas with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of CLas, which is of much importance for developing novel strategies to halt the spread of CLas, and therefore contribute to the efficient prevention and control of HLB.

Molecular Prevalence, Genetic Diversity, and Tissue Tropism of Bartonella Species in Small Mammals from Yunnan Province, China.

Bartonella is an intracellular parasitic zoonotic pathogen that can infect animals and cause a variety of human diseases. This study investigates Bartonella prevalence in small mammals in Yunnan Province, China, focusing on tissue tropism. A total of 333 small mammals were sampled from thirteen species, three orders, four families, and four genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified thirty, ten, and five strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in Episoriculus leucops (GS136). Analysis of the different tissues naturally infected by Bartonella species revealed varied copy numbers across different tissues, with the highest load in spleen tissue. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting the presence of extensive tissue tropism in Bartonella species naturally infecting small mammalian tissues.

Effects of Different Storage Times on the Stability of 12 Traditional Chinese Medicine Decoction Pieces.

As storage time increases, the quality of traditional Chinese medicines (TCMs) may change, and stability is an essential aspect of ensuring the safety and efficacy of TCMs. In this study, the effects of different storage times on the stability of 12 decoction pieces were evaluated. High-performance liquid chromatography was used to determine the contents of the active components in the 12 decoction pieces. The chemical composition data were analyzed using fingerprinting and clustering heatmap (CH). Results showed that during storage, significant variations (relative standard deviation > 10%) were observed in the levels of paeoniflorin in Paeoniae Radix Alba and Paeoniae Radix Rubra, hesperidin in Citri Reticulatae Pericarpium and Citri Reticulatae Pericarpium Viride, bufothionine in Siccus Bufo and chlorogenic acid in White Chrysanthemi Flos and Lonice Raejaponicae Caulis. However, calycosin-7-glucoside and calycosin in Astragali Radix Praeparata Cum Melle and chlorogenic acid in Lonicerae Japonicae Flos, Yellow Chrysanthemi Flos and Mori Folium were all <10%, which is consistent with the CH. Decoction pieces can be stored for up to six months, but it is recommended that volatile oil-containing and animal-based decoction pieces should not be stored for more than one month. This study provides new perspectives for the stability and quality control studies of TCM.

A C-type lectin with dual carbohydrate recognition domains functions in innate immune response in Asian corn borer, Ostrinia furnacalis.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Plasmodium vivax tryptophan-rich antigen reduces type I collagen secretion via the NF-κBp65 pathway in splenic fibroblasts.

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.