Spray Vaccination with a Newcastle Disease Virus (NDV)-Vectored Infectious Laryngotracheitis (ILT) Vaccine Protects Commercial Chickens from ILT in the Presence of Maternally Derived Antibodies.

Infectious laryngotracheitis (ILT) poses a significant threat to the poultry industry, and vaccines play an important role in protection. However, due to the increasing scale of poultry production, there is an urgent need to develop vaccines that are suitable for convenient immunization methods such as spraying. Previous studies have shown that Newcastle disease virus (NDV)-ILT vaccines administered via intranasal and intraocular routes to commercial chickens carrying maternally derived antibodies (MDAs) are still protective against ILT. In this study, a recombinant NDV (rNDV) was generated to express infectious laryngotracheitis virus (ILTV) glycoprotein B (gB), named rLS-gB, based on a full-length cDNA clone of the LaSota strain. The protective effect of different doses of rLS-gB administered by spray vaccination to commercial chickens at 1 day of age (DOA) was evaluated. The chickens were exposed to 160-µm aerosol particles for 10 min for spray vaccination, and no adverse reactions were observed after vaccination. Despite the presence of anti-NDV MDAs and anti-ILTV MDAs in chickens, the ILTV- and NDV-specific antibody titers were significantly greater in the vaccinated groups than in the unvaccinated group. After challenge with a virulent ILTV strain, no clinical signs were observed in the 107 EID50/ml group compared to the other groups. Furthermore, vaccination with 107 EID50/ml rLS-gB significantly reduced the ILTV viral load and ameliorated gross and microscopic lesions in the trachea of chickens. Overall, these results suggested that rLS-gB is a safe and efficient candidate spray vaccine for ILT and is especially suitable for scaled chicken farms.

METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer growth.

The objective of this study was to better characterize the role of the glutamine transporter SLC38A1 in cervical cancer and explore the underlying mechanisms. Data from public databases and clinical cervical cancer tissue samples were used to assess the expression of SLC38A1 and its prognostic significance. Immunohistochemical staining, qRT-PCR, and Western blotting were used to evaluate the expression of relevant genes and proteins. Cell viability, cell cycle, apoptosis, and intracellular glutamine content were measured using CCK-8, flow cytometry, and biochemical assays. Additionally, the RNA immunoprecipitation (RIP) assay was used to examine the impact of METTL3/IGF2BP3 on the m6A modification of the SLC38A1 3'UTR. Both cervical cancer specimens and cells showed significantly increased expression of SLC38A1 and its expression correlated with an unfavorable prognosis. Knockdown of SLC38A1 inhibited cell viability and cell cycle progression, induced apoptosis, and suppressed tumor growth in vivo. Glutaminase-1 inhibitor CB-839 reversed the effects of SLC38A1 overexpression. METTL3 promoted m6A modification of SLC38A1 and enhanced its mRNA stability through IGF2BP3 recruitment. Moreover, METTL3 silencing inhibited cell viability, cell cycle progression, intracellular glutamine content, and induced apoptosis, but these effects were reversed by SLC38A1 overexpression. In conclusion, METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer progression. SLC38A1 inhibition is a potential therapeutic strategy for cervical cancer.

Association of serum uric acid level with intracranial aneurysms: A Mendelian randomization study.

Objective: Numerous studies have posited the involvement of serum uric acid (SUA) in the pathogenesis and progression of various cardiovascular diseases, particularly aortic aneurysms. However, the casual effect of SUA level on intracranial aneurysms (IAs) was rarely studied. Consequently, we aimed to explore the causal association between SUA and IAs using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis with SUA as the exposure variable and IAs as the outcome variable. Genome-wide association study (GWAS) datasets for SUA were acquired from the Open GWAS catalog, including 389,404 European and 129,405 East Asian individuals. The dataset for IAs was sourced from a meta-analysis of GWASs comprising 317,636 individuals across different ancestral populations (European: 7495 cases and 71,934 controls; East Asian: 3259 cases and 234,948 controls). The MR analyses were performed according to populations (European and East Asian) and IAs status [unruptured IAs (uIAs) or aneurysmal subarachnoid hemorrhage (aSAH)], respectively. The inverse variance weighted (IVW) method was employed as primary analysis to discern causal estimates. Results: Our findings revealed that an elevated genetically predicted SUA level (mg/dL) correlated with an increased risk of IAs among the European population (OR = 1.29 [95%CI:1.05-1.57], P = 0.013) and East Asian population (OR = 1.56 [95%CI: 1.27-1.92], P < 0.001). Among European individuals, subgroup analysis indicated a persistent causal association of SUA with uIAs (OR = 1.50 [95%CI: 1.08-2.08], P = 0.015) and aSAH (OR = 1.26 [95%CI: 1.00-1.60], P = 0.049). However, subgroup analysis in East Asian populations was not conducted due to the lack of separate data on uIAs and aSAH. Conclusions: Our MR analysis demonstrated a causal relationship between elevated SUA levels and an amplified risk of IAs. Further rigorous investigations are imperative to provide evidence and elucidate the underlying mechanisms.

Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ. Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation. Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX. Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

The effect of life events on NSSI: the chain mediating effect of sleep disturbances and PLEs among Chinese college students.

This study aimed to explore the relationship between life events and non-suicidal self-injury (NSSI) in college students, as well as the mediating effect of sleep disturbances and psychotic-like experiences (PLEs). After excluding invalid questionnaires, 5,754 were retained, and the valid efficiency was 75.94%. The subjects were aged 16 to 29 years (M = 19.166; SD = 1.392), with 1,969 males (34.22%) and 3,785 females (65.78%). Life events, sleep disturbances, PLEs, and NSSI were assessed using standard scales. Data were analyzed by Pearson Correlation Analysis and bias-correction percentile Bootstrap method. The results show that (1) life events were significant positive predictors of NSSI, sleep disturbances, and PLEs; (2) sleep disturbances, PLEs, and the chain mediation between the two, were mediators between life events and NSSI. Life events are thus shown to be an important external factor influencing NSSI in university students, and this process is mediated through sleep disturbances, PLEs, and the chain between the two. Interventions for NSSI can therefore be made by improving college students' sleep quality and reducing PLEs.

Neonatal microglia transplantation at early stage but not late stage after traumatic brain injury shows protective effects in mice.

The transplantation of neonatal microglia suppresses neuroinflammation caused by traumatic brain injury (TBI). This research aimed to explore the optimal time point of neonatal microglia transplantation for the best effect on the improvement of long-term cognitive function and inflammatory response in mouse models. qPCR and immunoblotting showed that the level of Iba1 gradually increased to the highest on day 7 and then gradually declined in TBI mice. Furthermore, it was observed that the level of CD86 and TNF-α increased to the highest after 7 days and subsequently was maintained until day 21, whereas the level of CD206 and IL-10 increased to the highest after 24 h and subsequently decreased until day 21 by qPCR and enzyme-linked immunosorbent assay. Afterward, it was shown that the neonatal microglia transplantation within 1 h significantly attenuated anxiety-like behavior and improved cognitive impairments in TBI mice. Mechanism exploration showed that the neonatal microglia could significantly decrease the level of cleaved caspase-3, M1/M2 polarization, and inflammatory cytokine (TNF-α) while increasing the level of anti-inflammatory factor IL-10 in TBI mice after transplantation within 1 h. Here, our findings demonstrated that neonatal microglia transplantation within 1 h significantly attenuated anxiety-like behavior and cognitive impairments caused by TBI.NEW & NOTEWORTHY The study demonstrated that neonatal microglia transplantation within 1 h significantly inhibited the pathogenesis of traumatic brain injury (TBI) in mouse models through inhibition of M1 polarization and promotion of M2 polarization.

Schizandrin A attenuates early brain injury following subarachnoid hemorrhage through suppressing neuroinflammation.

BACKGROUND: Early brain injury (EBI) is the vital factor in determining the outcome of subarachnoid hemorrhage (SAH). Schizandrin A (Sch A), the bioactive ingredient extracted from Schisandra chinensis, has been proved to exert beneficial effects in multiple human diseases. However, the effect of Sch A on SAH remains unknown. The current study was designed to explored role and mechanism of Sch A in the pathophysiological process of EBI following SAH. METHOD: A total of 74 male C57BL/6 J mice were subjected to endovascular perforation to establish the SAH model. Different dosages of Sch A were administrated post-modeling. The post-modeling assessments included neurological test, brain water content, RT-PCR, immunofluorescence, Nissl staining. Oxygenated hemoglobin was introduced into microglia to establish a SAH model in vitro. RESULT: Sch A significantly alleviated SAH-induced brain edema and neurological impairment. Moreover, application of Sch A remarkably inhibited SAH-induced neuroinflammation, evidenced by the decreased microglial activation and downregulated TNF-α, IL-1ß and IL-6 and expression. Additionally, Sch A, both in vivo and in vitro, protected neurons against SAH-induced inflammatory injury. Mechanismly, administration of Sch A inhibited miR-155/NF-κB axis and attenuated neuroinflammation, as well as alleviating neuronal injury. CONCLUSION: Our data suggested that Sch A could attenuated EBI following SAH via modulating neuroinflammation. The anti-inflammatory effect was exerted, at least partly through the miR-155/NF-κB axis, which may shed light on a possible therapeutic target for SAH.

Astragaloside IV Inhibits Rotenone-Induced α-syn Presentation and the CD4 T-Cell Immune Response.

The increased α-synuclein (α-syn)-dependent activation of CD4 T cells leads to the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Astragaloside IV (AS-IV) protects DA neurons against neuroinflammation. The effects of AS-IV on CD4 T-cell-mediated immune responses in PD remain unknown. Rotenone (ROT) injected unilaterally into the substantia nigra pars compacta (SNc) of rats induced PD. AS-IV (20 mg/kg) was intraperitoneally injected once a day for 14 days. The limb hanging test and rotarod test were performed to evaluate the alteration of behavior at 4 and 6 weeks. Total gastrointestinal transit tests were performed at 4 weeks. Western blotting was used to detect the expression of proinflammatory cytokine proteins. Immunofluorescence staining was conducted to test the expression and localization of major histocompatibility complex class II (MHCII), cleaved caspase-1 and α-syn in astrocytes. Flow cytometry analysis, immunohistochemistry and immunofluorescence staining were used to measure the expression of CD4 T-cell subsets in the SN. The application of AS-IV protected against the loss of DA neurons and behavioral deficits in ROT-induced PD rat models. AS-IV administration inhibited the aggregation of α-syn in DA neurons and the expression of proinflammatory cytokines such as TNF-α, IL-18, IL-6 and IL-1ß. AS-IV decreased the activation of CD4 T cells and three CD4 T-cell subsets: Tfh, Treg and Th1. AS-IV interrupted the ROT-induced interaction between astrocytes and CD4 T cells and the colocalization of MHCII and α-syn in astrocytes. AS-IV inhibited the expression of α-syn in astrocytes and the colocalization of α-syn and cleaved caspase-1 in astrocytes. AS-IV prevents the loss of DA neurons in PD by inhibiting the activation of α-syn-specific CD4 T cells, which is regulated by MHCII-mediated antigen presentation in astrocytes.

Fabrication of self-assembled micelles based on amphiphilic oxidized sodium alginate grafted oleoamine derivatives via Schiff base reduction amination reaction for delivery of hydrophobic food active ingredients.

The application of hydrophobic ß-carotene in the food industry are limited due to its susceptibility to light, high temperature, pH value, and other factors, leading to poor stability and low bioavailability. To address this problem, we adopt a more green and environmentally friendly reducing agent, 2-methylpyridine borane complex (pic-BH3), instead of traditional sodium borohydride, to achieve the simple green and efficient synthesis of amphiphilic oxidized sodium alginate grafted oleoamine derivatives (OSAOLA) through the reduction amination reaction of Schiff base. The resultant OSAOLA with the degree of substitution (DS) of 7.2 %, 23.6 %, and 38.8 % were synthesized, and their CMC values ranged from 0.0095 to 0.062 mg/mL, indicating excellent self-assembly capability in aqueous solution. Meanwhile, OSAOLA showed no obvious cytotoxicity to RAW 264.7 cells, thus revealing good biocompatibility. Furthermore, ß-carotene, as the hydrophobic active ingredients in foods was successfully encapsulated in the OSAOLA micelles by ultrasonic-dialysis method. The prepared drug-loaded OSAOLA micelles could maintain good stability when stored at room temperature for 7 d. Additionally, they were able to continuously release ß-carotene and exert long-term effects in pH 7.4 PBS at 37 °C, effectively improving the bioavailability of ß-carotene, which exhibited tremendous application potential in functional food and biomedical fields.

Virus-Like Particles Based on the Novel Goose Parvovirus (NGPV) VP2 Protein Protect Ducks against NGPV Challenge.

Novel goose parvovirus (NGPV), a genetic variant of goose parvovirus, has been spreading throughout China since 2015 and mainly infects ducklings with the symptoms of growth retardation, beak atrophy, and protruding tongue, leading to huge economic losses every year. A safe and effective vaccine is urgently needed to control NGPV infection. In this study, virus-like particles (VLPs) of NPGV were assembled and evaluated for their immunogenicity. The VP2 protein of NGPV was expressed in Spodoptera frugiperda insect cells using baculovirus as vector. The VP2 protein was efficiently expressed in the nucleus of insect cells, and the particles with a circular or hexagonal shape and a diameter of approximately 30 nm, similar to the NGPV virion, were observed using transmission electron microscopy (TEM). The purified particles were confirmed to be composed of VP2 using western blot and TEM, indicating that the VLPs of NGPV were successfully assembled. Furthermore, the immunogenicity of the VLPs of NGPV was evaluated in Cherry Valley ducks. The level of NGPV serum antibodies increased significantly at 1-4 weeks post-immunization. No clinical symptoms or deaths of ducks occurred in all groups after being challenged with NGPV at 4 weeks post-immunization. There was no viral shedding in the immunized group. However, viral shedding was detected at 3-7 days post-challenge in the non-immunized group. Moreover, VLPs can protect ducks from histopathological lesions caused by NGPV and significantly reduce viral load in tissue at 5 days post-challenge. Based on these findings, NGPV VLPs are promising candidates for vaccines against NGPV.

Integrated analysis reveals the potential of cluster of differentiation 86 as a key biomarker in high-grade glioma.

This study aimed to evaluate the potential of cluster of differentiation 86 (CD86) as a biomarker in high-grade glioma (HGG). The TCGA and TCIA databases were used to obtain the CD86 expression value, clinical data, and MRI images of HGG patients. Prognostic values were assessed by the Kaplan-Meier method, Receiver operating characteristic curve (ROC), Cox regression, logistic regression, and nomogram analyses. CD86-associated pathways were also explored. We found that CD86 was significantly upregulated in HGG compared with the normal group. Survival analysis showed a significant association between CD86 high expression and shorter overall survival time. Its independent prognostic value was also confirmed. These results suggested the possibility of CD86 as a biomarker in HGG. We also innovatively established 2 radiomics models with Support Vector Machine (SVM) and Logistic regression (LR) algorithms to predict the CD86 expression. The 2 models containing 5 optimal features by SVM and LR methods showed similar favorable performance in predicting CD86 expression in the training set, and their performance were also confirmed in validation set. These results indicated the successful construction of a radiomics model for non-invasively predicting biomarker in HGG. Finally, pathway analysis indicated that CD86 might be involved in the natural killer cell-mediated cytotoxicity in HGG progression.

Network meta-analysis of first-line thrombectomy strategy for acute posterior circulation strokes: a preliminary evaluation for combined approach.

Objective: Thrombectomy may provide superior results compared to best medical care for acute posterior circulation strokes (PCS). Contact aspiration (CA), stent retriever (SR), and combined SR + CA (SRA) are commonly employed as first-line techniques. However, the optimal strategy and the role of SRA remain uncertain. Methods: Systematic searching was conducted in three databases (PubMed, Embase, and Cochrane). Network meta-analyzes were performed using random-effects models. The reperfusion and clinical outcomes were compared. Pooled outcomes were presented as odds ratios (OR) with 95% confidence intervals (CI). Rankograms with surface under the cumulative ranking curve (SUCRA) were calculated. Results: Seventeen studies were included, involving a total of 645 patients who received first-line CA, 850 patients who received SR, and 166 patients who received SRA. Regarding final recanalization outcomes, both first-line SRA (OR = 3.2, 95%CI 1.4-11.0) and CA (OR = 2.1, 95%CI 1.3-3.7) demonstrated superiority over SR in achieving successful reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3], with values of SUCRA 91.1, 58.5, and 0.4%, respectively. In addition, first-line SRA showed an advantage in achieving final mTICI 2c/3 compared to CA (OR = 3.6, 95%CI 0.99-16.0) and SR (OR = 6.4, 95%CI 1.3-35.0), with SUCRA value of 98.0, 44.7, and 7.2%, respectively. Regarding reperfusion outcome after the first pass, SRA also achieved a higher rate of mTICI 3 than SR (OR = 4.1, 95%CI 1.3-14.0), while CA did not (SUCRA 97.4, 4.6, 48.0%). In terms of safety outcomes, first-line CA was associated with a lower incidence of symptomatic intracranial hemorrhage (sICH) compared to SR (OR = 0.38, 95%CI 0.1-1.0), whereas the SRA technique did not (SUCRA 15.6, 78.6, 55.9%). Regarding clinical prognosis, first-line CA achieved a higher proportion of functional independence (modified Rankin Scale (mRS) 0-2) at 90 days than SR (OR = 1.4, 95%CI 1.1-1.9), whereas SRA did not (SUCRA 90.5, 17.4, 42.1%). Conclusion: For acute PCS, a first-line CA strategy yielded better results in terms of final successful reperfusion and 90-day functional independence compared to SR. As the combined technique, first-line SRA was associated with superior first-pass and final reperfusion outcomes compared to SR. However, no significant difference was observed in functional independence achieved by first-line SRA compared to the other two strategies. Further high-quality studies are warranted.

Occurrence and Genotypic Identification of Blastocystis spp., Enterocytozoon bieneusi, and Giardia duodenalis in Leizhou Black Goats in Zhanjiang City, Guangdong Province, China.

Blastocystis spp., Enterocytozoon bieneusi, and Giardia duodenalis are three common zoonotic intestinal parasites that cause severe diarrhea and enteric diseases. Leizhou black goats are characterized by a high reproductive rate, fast growth, and good meat quality, making them one of the pre-eminent goat breeds in China. Goats are reportedly common reservoirs of these three intestinal pathogens, but no information on their prevalence or genotypic distributions in black goats in Guangdong Province, China, is available. A total of 226 fecal samples were collected from goats in Zhanjiang city and genomic DNA was extracted from them. The presence of the three pathogens was detected using nested PCR targeting the sequences encoding SSU rRNA (Blastocystis spp.), the internal transcribed spacer of rRNA (ITS; E. bieneusi), as well as beta-giardin, glutamate dehydrogenase, and triosephosphate isomerase (G. duodenalis). All PCR products were sequenced to determine the species and genotypes of the organisms. The total prevalence rates of Blastocystis spp., E. bieneusi, and G. duodenalis were 33.63% (76/226), 17.70% (40/226), and 24.78% (56/226), respectively. Four subtypes of Blastocystis spp. were detected: ST5 (n = 6), ST10 (n = 50), ST14 (n = 14), and ST21 (n = 6). Among them, ST10 was the dominant genotype, accounting for 65.79% of strains, followed by the genotypes ST14 (18.42%), zoonotic ST5 (7.89%), and ST21 (7.89%). Four genotypes of E. bieneusi were detected: CHG3 (n = 32), CM21 (n = 4), CHG1 (n = 2), and ET-L2 (n = 2). Among these, CHG3 was the dominant genotype. Assemblage E (n = 54) and concurrent assemblages A and E (n = 2) were identified in the G. duodenalis-positive goats using multilocus genotyping. Blastocystis spp., E. bieneusi, and G. duodenalis infections were common in Leizhou black goats, all of which have zoonotic genotypes, indicating the potential risk of zoonotic transmission. Our results provide basic data for the prevention and control of these three intestinal pathogens. Further studies are required to better understand their genetic characteristics and zoonotic potential in Guangdong Province.

Construction and Evaluation of Alginate Dialdehyde Grafted RGD Derivatives/Polyvinyl Alcohol/Cellulose Nanocrystals IPN Composite Hydrogels.

To enhance the mechanical strength and cell adhesion of alginate hydrogel, making it satisfy the requirements of an ideal tissue engineering scaffold, the grafting of Arg-Gly-Asp (RGD) polypeptide sequence onto the alginate molecular chain was conducted by oxidation of sodium periodate and subsequent reduction amination of 2-methylpyridine borane complex (2-PBC) to synthesize alginate dialdehyde grafted RGD derivatives (ADA-RGD) with good cellular affinity. The interpenetrating network (IPN) composite hydrogels of alginate/polyvinyl alcohol/cellulose nanocrystals (ALG/PVA/CNCs) were fabricated through a physical mixture of ion cross-linking of sodium alginate (SA) with hydroxyapatite/D-glucono-δ-lactone (HAP/GDL), and physical cross-linking of polyvinyl alcohol (PVA) by a freezing/thawing method, using cellulose nanocrystals (CNCs) as the reinforcement agent. The effects of the addition of CNCs and different contents of PVA on the morphology, thermal stability, mechanical properties, swelling, biodegradability, and cell compatibility of the IPN composite hydrogels were investigated, and the effect of RGD grafting on the biological properties of the IPN composite hydrogels was also studied. The resultant IPN ALG/PVA/CNCs composite hydrogels exhibited good pore structure and regular 3D morphology, whose pore size and porosity could be regulated by adjusting PVA content and the addition of CNCs. By increasing the PVA content, the number of physical cross-linking points in PVA increased, resulting in greater stress support for the IPN composite hydrogels of ALG/PVA/CNCs and consequently improving their mechanical characteristics. The creation of the IPN ALG/PVA/CNCs composite hydrogels' physical cross-linking network through intramolecular or intermolecular hydrogen bonding led to improved thermal resistance and reduced swelling and biodegradation rate. Conversely, the ADA-RGD/PVA/CNCs IPN composite hydrogels exhibited a quicker degradation rate, attributed to the elimination of ADA-RGD by alkali. The results of the in vitro cytocompatibility showed that ALG/0.5PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels showed better proliferative activity in comparison with other composite hydrogels, while ALG/PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels displayed obvious proliferation effects, indicating that PVA, CNCs, and ADA-RGD with good biocompatibility were conducive to cell proliferation and differentiation for the IPN composite hydrogels.

Corrigendum: CREB5 hypermethylation involved in the ganglioside GM1 therapy of Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1122647.].

Serotonergic multilocus genetic variation moderates the association between interpersonal relationship and adolescent depressive symptoms.

BACKGROUND: Research suggests that genetic variants linked to serotonin functioning moderate the association between environmental stressors and depressive symptoms, but examining gene-environment interactions with single polymorphisms limits power. METHODS: A multilocus genetic profile score (MGPS) approach to measuring serotonergic multilocus genetic variation and examined interactions with interpersonal relationship, insomnia with depressive symptoms as outcomes in an adolescent sample (average age = 14.15 ± 0.63 years since first measurement; range: 13 to 15). RESULTS: (1) interpersonal relationship predicted adolescent depressive symptoms; (2) insomnia mediated the effect of interpersonal relationships on adolescent depressive symptoms; (3) the THP2 gene rs4570625 polymorphism G allele was a key risk factor for depressive symptom, and the MGPS moderated the effects of teacher-student relationship and insomnia on adolescent depressive symptom. Specifically, as the MGPS increased, the effects of insomnia on adolescent depressive symptom were enhanced; further, when the MGPS score increased, the effect of teacher-student relationship on depression showed a similar phenomenon with an increased slope and enhanced prediction; and (4) the results of sensitivity analysis showed that multilocus genetic interaction with the environment had a better explanatory power and stability for depression than single polymorphism studies. CONCLUSION: MGPS provides substantial power to examine gene-environmental interactions linked to affective outcomes among adolescents.

Glioblastoma-on-a-chip construction and therapeutic applications.

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment in vivo using traditional in vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking in vivo functions of GBM cells. This technology has shown great potential for applications in personalized precision medicine and GBM immunotherapy. In recent years, there have been efforts to construct GBM-on-a-chip models based on microfluidics and bioprinting. A number of research teams have begun to use GBM-on-a-chip models for the investigation of GBM progression mechanisms, drug candidates, and therapeutic approaches. This review first briefly discusses the use of microfluidics and bioprinting technologies for GBM-on-a-chip construction. Second, we classify non-surgical treatments for GBM in pre-clinical research into three categories (chemotherapy, immunotherapy and other therapies) and focus on the use of GBM-on-a-chip in research for each category. Last, we demonstrate that organ-on-a-chip technology in therapeutic field is still in its initial stage and provide future perspectives for research directions in the field.

Pretreatment lymphocyte-to-monocyte ratio as a prognostic factor and influence on dose-effect in fractionated stereotactic radiotherapy for oligometastatic brain metastases in non-small cell lung cancer patients.

Background: Studies on the prognostic factors for patients with brain oligo-metastasis treated with fractionated stereotactic radiotherapy (FSRT) usually focus on the size of metastatic tumor and radiation dose. Some inflammatory indicators have predictive value in non-small cell lung cancer (NSCLC) with brain metastasis receiving stereotactic radiotherapy. However, the prognostic value of inflammatory indicators in NSCLC patients with brain oligo-metastasis treated with FSRT, and their effect on radiotherapy dose is unknown. Methods: A total of 95 advanced NSCLC patients with brain oligo-metastasis who had undergone FSRT treatment at Ningbo Medical Center Lihuili Hospital between January 2015 and April 2022 were enrolled into the study. Neutrophil to lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), tumor diameter and biologically effective dose (BED10) were analyzed using Chi-square test. Univariate and multivariate Cox regressions were used to identify predictors of survival. Results: Tumor diameter (< 2 cm), BED10 (≥ 48Gy) and LMR (≥ 4) were found to be independently associated with good intracranial local control survival (i-LCS) through multivariate analysis. The median i-LCS was longer in patients with 2 independent risk factors (tumor diameter ≥ 2 and LMR < 4) administered with BED10 > 53.6Gy compared with patients administered with BED10 ≤ 53.6Gy (20.7 months vs 12.0 months, P = 0.042). LMR ≥ 4 (P = 0.019) and positivity for driver gene mutations (P = 0.011) were independently associated with better overall survival (OS). Conclusions: LMR is an independent prognostic factor of i-LCS and OS in NSCLC patients with brain oligo-metastasis treated with FSRT. Patients with tumor diameter ≥ 2 and LMR < 4 should be treated with BED10 greater than 53.6Gy.

C-terminal truncation of the hemagglutinin-neuraminidase (HN) protein enhances the virulence and immunogenicity of Newcastle disease virus (NDV) vaccine strain V4.

The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is a multifunctional protein with receptor recognition ability that plays an important role in the infection of cells by NDV. An alignment of NDV HN protein sequences of different genotypes showed that vaccine strains of NDV, such as the LaSota strain, generally have an HN protein of 577 amino acids. In comparison, the HN protein of the V4 strain has 616 amino acids, with 39 more amino acids at the C-terminus. In this study, we generated a recombinant NDV (rNDV) with a 39-amino-acid truncation at the HN C-terminus based on the full-length cDNA clone of the V4 strain. This rNDV, named rV4-HN-tr, displayed thermostability similar to that of the parental V4 strain. However, growth kinetics and pathogenicity analysis suggested that rV4-HN-tr is more virulent than the V4 strain. Notably, the C-terminus of HN affected the ability of the virus to adsorb onto cells. Structural predictions further suggested that the C-terminus of HN may obstruct the sialic acid binding site. Immunization of chickens with rV4-HN-tr induced a 3.5-fold higher level of NDV-specific antibodies than that obtained with the V4 strain and provided 100% immune protection against NDV challenge. Our study suggests that rV4-HN-tr is a thermostable, safe, and highly efficient vaccine candidate against Newcastle disease.

CREB5 hypermethylation involved in the ganglioside GM1 therapy of Parkinson's disease.

Introduction: The treatment with monosialotetrahexosylganglioside (GM1) improves the symptoms of Parkinson's disease (PD). The alteration of DNA methylation in the blood was examined to investigate epigenetic modification by GM1 treatment. Methods: After a 28-day continuous intravenous infusion of GM1 (100mg), the motor and non-motor symptoms were evaluated by UPDRS III, Mini-mental state examination (MMSE) scores, FS-14, SCOPA-AUT, and PDQ-8. Moreover, blood samples were collected and PBMC was isolated. Genome-wide DNA methylation was performed by an 850K BeadChip. RNA levels and apoptosis were examined by RT-PCR and flow cytometry in rotenone-based cell models. The CREB5 plasmid was transfected by electroporation into SH-SY5Y cells. We also identified 235 methylation variable positions achieving genome-wide significance in 717558 differentially methylated positions (DMPs) (P = 0.0003) in comparison of pre-treatment with post-treatment measurements (statistical analysis paired-samples t-test). Results: By searching the Gene Expression Omnibus (GEO) dataset and GWAS, 23 methylation variable positions were screened. Moreover, there are 7 hypomethylated methylation variable positions correlated with the scores of motor symptoms (UPDRS III scale). According to KEGG pathways enrichment analysis, the methylated genes CACNA1B (hypomethylated), CREB5 (hypermethylated), GNB4 (hypomethylated), and PPP2R5A (hypomethylated) were enriched in the dopaminergic synapse pathway. Pretreated with GM1 (80 µM) for 1 h, cell apoptosis and impaired neurite outgrowth were inhibited in rotenone-induced PD cell models. The RNA expression of CREB5 was increased in rotenone-treated SH-SY5Y cells. GM1 treatment decreased rotenone-induced CREB5 gene expression. The enhancement of CREB5 gene expression suppressed the protective role of GM1 in rotenone-induced cell apoptosis. Discussion: The application of GM1 improves the motor and non-motor symptoms of PD associated with the decreased CREB5 expression and the hypermethylation of CREB5. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=120582t, identifier ChiCTR2100042537.