Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge.

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.

Establishment of an indirect competitive immunoassay for the detection of dicamba based on a highly specific nanobody.

Dicamba, a traditional highly effective and low toxicity herbicide, has gained new life with the development of dicamba-tolerant transgenic crops in recent years. However, dicamba is highly volatile and therefore easy to cause drift damage to sensitive crops. The development of efficient and sensitive detection methods is essential for monitoring of trace dicamba in the environment. Nanobody-based immunoassay plays an important role in on-site detection of pesticides. However, now rapid and sensitive immunoassay methods based on nanobody for dicamba detection were lacking. In this study, the nanobodies specifically recognizing dicamba were successfully obtained by immunising camels and phage display library construction, and then an indirect competitive immunoassay based on Nb-242 was constructed with IC50 of 0.93 µg/mL and a linear range of 0.11-8.01 µg/mL. Nb-242 had good specificity with no cross-reactivities against the dicamba analogs other than 2,3,6-trichlorobenzoic acid and the developed immnoassay had a good correlation with the standard HPLC in the spike-recovery studies. Finally, the key amino acid Ala 123, Tyr 55, Tyr 59 and Arg 72 of Nb-242 that specifically recognizing and binding with dicamba were identified by homologous modeling and molecular docking, laying an important foundation for further structural modification of Nb-242. This study has important guiding significance for constructing immunoassay method of dicamba based on nanobody and provides a sensitive, specific, and reliable detection method that is suitable for the detection of dicamba in the environment.

Development of an immunoassay based on a specific antibody for the detection of diphenyl ether herbicide fomesafen.

Fomesafen belongs to the diphenyl ether herbicide, and is widely used in the control of broadleaf weeds in crop fields due to its high efficiency and good selectivity. The residual of fomesafen in soil has a toxic effect on subsequent sensitive crops and the microbial community structure because of its long residual period. Therefore, an efficient method for detecting fomesafen is critical to guide the correct and reasonable use of this herbicide. Rapid and sensitive immunoassay methods for fomesafen is unavailable due to the lack of specific antibody. In this study, a specific antibody for fomesafen was generated based on rational design of haptens and a sensitive immunoassay method was established. The half maximal inhibitory concentration (IC50) of the immunoassay was 39 ng/mL with a linear range (IC10-90) of 1.92-779.8 ng/mL. In addition, the developed assay had a good correlation with the standard UPLC-MS/MS both in the spike-recovery studies and in the detection of real soil samples. Overall, the developed indirect competitive enzyme immunoassay reported here is important for detecting and quantifying fomesafen contamination in soil and other environmental samples with good sensitivity and high reproducibility.

Clinical efficacy and safety of endovascular treatment for patients with wake-up stroke with large vessel occlusion guided by NCCT-ASPECTS.

OBJECTIVE: To evaluate the clinical efficacy and safety of 6 to 24 h endovascular therapy (EVT) in patients with wake-up stroke (WUS) with acute large vessel occlusion (LVO) of the anterior circulation guided by noncontrast computed tomography-Alberta stroke program early CT score (NCCT-ASPECTS). METHODS: Fifty-three patients with WUS with acute LVO of the anterior circulation who were treated at the Sir Run Run Shaw Hospital of Zhejiang Medical College from January 2018 to March 2021 were retrospectively analyzed. The patients were divided into NCCT-ASPECTS or CT perfusion groups. Baseline data, perioperative data, and 90-d prognostic information were compared between the two groups. Multivariable logistic regression analysis was used to determine the independent factors influencing outcomes. RESULTS: There were no significant differences in the good prognosis, symptomatic intracranial hemorrhage, and mortality rates between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the puncture-recanalization time was an independent factor for good prognosis. CONCLUSION: Based on NCCT-ASPECTS guidance, EVT in patients with WUS for acute LVO of the anterior circulation within 6 to 24 h may be safe and effective.

Research Progress on the Species and Diversity of Ants and Their Three Tropisms.

Ants are one of the largest insect groups, with the most species and individuals in the world, and they have an important ecological function. Ants are not only an important part of the food chains but are also one of the main decomposers on the Earth; they can also improve soil fertility, etc. However, some species of ants are harmful to human beings, which leads to people's panic or worry about coming into contact with these insects during their daily home life or in their tourism or leisure activities. The presence of ants in indoor living facilities and in outdoor green spaces, parks, gardens, and tourist attractions seriously interferes with the leisure life and entertainment activities of all people (especially children). How can we control ants in these environments? Do we kill them by spraying insecticides, or do we adopt green prevention and control technology for the ecological management of ants? This topic is related to healthy life for the public and the protection of the ecological environment. In this paper, the species and diversity of ants are introduced, and research progress regarding ant tropism is introduced according to the three aspects of phototaxis, chromotaxis, and chemotaxis (i.e., "3-tropisms"). The research on repellent substances from plants and insects and the related ant attractants are also summarized, analyzed, and discussed, in order to help the research and application of green prevention and control technology for ant diversity protection and conservation.

Multilayered regulation of secondary metabolism in medicinal plants.

Medicinal plants represent a huge reservoir of secondary metabolites (SMs), substances with significant pharmaceutical and industrial potential. However, obtaining secondary metabolites remains a challenge due to their low-yield accumulation in medicinal plants; moreover, these secondary metabolites are produced through tightly coordinated pathways involving many spatiotemporally and environmentally regulated steps. The first regulatory layer involves a complex network of transcription factors; a second, more recently discovered layer of complexity in the regulation of SMs is epigenetic modification, such as DNA methylation, histone modification and small RNA-based mechanisms, which can jointly or separately influence secondary metabolites by regulating gene expression. Here, we summarize the findings in the fields of genetic and epigenetic regulation with a special emphasis on SMs in medicinal plants, providing a new perspective on the multiple layers of regulation of gene expression.

Study on extraction technology and antioxidant activity of total alkaloids from Hemsleya chinensis based on orthogonal design and BP neural network.

In this study, total alkaloids from Hemsleya chinensis were extracted and tested for their antioxidant properties. To optimize extraction methods, a single factor experiment was conducted to determine the total alkaloid concentrations of H. chinensis using the L9 (34) orthogonal design test method and the BP neural network (BPNN), resulting in the optimum extraction conditions for total alkaloids. The optimal conditions for H. chinensis alkaloids extraction with acid water are: HCl concentration is 0.50 %, extraction temperature is 85 °C, material-liquid ratio is 1:64.5, and extraction rate of alkaloids is 0.2785 ± 0.0003 mg/mL. The alkaloid from H. chinensis exhibited antioxidant activity in a quantity-effect relationship with activity. These findings showed that the procedure to be reasonable, the alkaloid extraction efficiency to be high, and the method could be used to extract the alkaloids of H. chinensis, improving the development of natural and healthy medicinal resources for the pharmaceutical and food industries.

Study on the effect of licochalcone A on intestinal flora in type 2 diabetes mellitus mice based on 16S rRNA technology.

Licorice, has a long history in China where it has various uses, including as a medicine, and is often widely consumed as a food ingredient. Licorice is rich in various active components, including polysaccharides, triterpenoids, alkaloids, and nucleosides, among which licochalcone A (LicA) is an active component with multiple physiological effects. Previous studies from our research group have shown that LicA can significantly improve glucose and lipid metabolism and related complications in Type 2 diabetes mellitus (T2DM) mice. However, research on the mechanism of LicA in T2DM mice based on intestinal flora has not been carried out in depth. Therefore, in this study, LicA was taken as the research object and the effects of LicA on glucose and lipid metabolism and intestinal flora in T2DM mice induced by streptozotocin (STZ)/high-fat feed (HFD) were explored. The results indicated that LicA could reduce serum TC, TG, and LDL-C levels, increase HDL-C levels, reduce blood glucose, and improve insulin resistance and glucose tolerance. LicA also alleviated pathological damage to the liver. The results also showed that LicA significantly affected the intestinal microbiota composition and increased the α diversity index. ß Diversity analysis showed that after the intervention of LicA, the composition of intestinal flora was significantly different from that in the T2DM model group. Correlation analysis showed that the changes in glucose and lipid metabolism parameters in mice were significantly correlated with the relative abundance of Firmicutes, Bacteroidetes, Helicobacter, and Lachnospiraceae (p < 0.01). Analysis of key bacteria showed that LicA could significantly promote the growth of beneficial bacteria, such as Bifidobacterium, Turicibacter, Blautia, and Faecococcus, and inhibit the growth of harmful bacteria, such as Enterococcus, Dorea, and Arachnococcus. In conclusion, it was confirmed that LicA reversed the imbalanced intestinal flora, and increased the richness and diversity of the species in T2DM mice.

EbbHLH80 Enhances Salt Responses by Up-Regulating Flavonoid Accumulation and Modulating ROS Levels.

bHLH transcription factors are involved in multiple aspects of plant biology, such as the response to abiotic stress. Erigeron breviscapus is a composite plant, and its rich flavonoids have strong preventive and therapeutic effects on cardio cerebral vascular disease. EbbHLH80, a gene from E. breviscapus that positively regulates flavonoid synthesis, was previously characterized. However, it is unclear whether EbbHLH80 increases flavonoid accumulation, which affects salt tolerance. The function of EbbHLH80 in transgenic tobacco seeds was identified by phylogenetic analysis and metabolome-transcriptome analysis. We investigated the role of EbbHLH80 in salt stress response. Our results showed that the expression of EbbHLH80 increased following salt treatment. Integrating the metabolome and transcriptome analysis of EbbHLH80-OE and Yunyan 87 (WT) seeds, we identified several genes and metabolites related to flavonoid biosynthesis and salt stress. Moreover, EbbHLH80-OE plants displayed higher salt tolerance than wild-type plants during seed germination and seedling growth. After salt treatment, transgenic tobacco had significantly lower levels of reactive oxygen species (ROS) than WT, with enhanced levels of antioxidant enzyme expression. Altogether, our results demonstrated that EbbHLH80 might be a positive regulator, promoting salt tolerance by modulating ROS scavenging and increasing stress-responsive genes.

Site-directed mutagenesis identified the key active site residues of 2,3-oxidosqualene cyclase HcOSC6 responsible for cucurbitacins biosynthesis in Hemsleya chinensis.

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

Staged endovascular recanalization for symptomatic atherosclerotic non-acutely occluded internal carotid artery.

OBJECTIVE: Symptomatic "non-acutely" occluded internal carotid artery (NAOICA) results in stroke, cognitive impairment, and hemicerebral atrophy through cerebral hypoperfusion and artery-to-artery embolism. Atherosclerosis is the main cause of NAOICA. Conventional one-stage endovascular recanalization showed effectiveness but was plagued by many challenges. This retrospective analysis reports the technical feasibility and outcomes of the staged endovascular recanalization in patients with NAOICA. METHODS: Eight consecutive patients with atherosclerotic NAOICA and ipsilateral ischemic stroke within 3 months between January 2019 and March 2022 were retrospectively reviewed. The patients (all males, with a mean age of 64.6 years) underwent staged endovascular recanalization 13 to 56 days after documented occlusion by imaging techniques (mean 28.8 days); the mean follow-up period was 20 months (range: 6-28). The approach of the staged intervention was as follows. In the first stage, the occluded ICA was successfully recanalized using the simple small balloon dilation technique. In the second stage, angioplasty with a stent implant was performed with >50% residual stenosis in the initial segment or ≥70% residual stenosis in the C2-C5 segment. The technical success rate, the incidence of clinical adverse events (any stroke, death, cerebral hyperperfusion), and long-term in-stent stenosis (ISR) and reocclusion rates were evaluated. RESULTS: Technical success was achieved in seven patients, with early reocclusion occurring in one patient after the first-stage intervention. There were no adverse events observed within 30 days (0%), and long-term reocclusion and long-term ISR rates were both 14% (1/7). However, all patients developed iatrogenic arterial dissections during the first stage, indicating the challenge of reaching the true lumen through the occlusion site without damaging the intima. Based on the National Heart, Lung and Blood Institute (NHLBI) classification, there were two type A, four type B, three type C, and two type D dissections. The mean time interval between the two stages was 46.1 days (21-152 days). All type A and B dissections resolved spontaneously after ≥3 weeks of dual antiplatelet therapy, whereas most type C and all type D dissections did not heal spontaneously before the second stage. Also, one type C dissection led to reocclusion. This observation suggested that dissections without flow limit and persistent vessel staining or extravasation could be clinically observed, while severe dissections (characterized as type C or greater) required prompt stenting rather than conservative treatment. Performing high-resolution MRI preoperatively to exclude fresh thrombus in the occluded vessel segment is indispensable in selecting appropriate candidates for endovascular recanalization. This could avoid downstream embolism during the interventional procedure. CONCLUSIONS: This retrospective study found that staged endovascular recanalization for symptomatic atherosclerotic NAOICA may be feasible with an acceptable technical success rate and a low complication rate in the selected candidates.

Development of immunoassay based on a specific antibody for sensitive detection of nicosulfuron in environment.

Nicosulfuron, one of the most widely used selective herbicides in corn field, can effectively control annual and perennial grass weeds, sedges, and some broadleaf weeds. The residual phytotoxicity of nicosulfuron in soil and water has become increasingly prominent. Therefore, an efficient method for detection of nicosulfuron was critical to ensure the sustainable and healthy development of agriculture and the ecological environment. In this paper, five nicosulfuron haptens which contained carboxyl group or aldehyde groups were designed and synthesized, and an indirect competitive immunoassay was developed for the first time. The assay showed an IC50 of 8.42 ng/mL and had negligible cross reactivities toward other sulfonylurea herbicides. In the spike and recovery studies, the recovery rate from soil samples was 95 %-104 %, and that of wheat roots was 92 %-98 %, which showed a good correlation with LC-MS analysis for nicosulfuron. The immunoassay was then used to quantify nicosulfuron concentration which could cause the obvious phytotoxic symptoms to wheat. Obvious symptoms of nicosulfuron phytotoxicity in wheat root was observed at the concentration of 0.068 ± 0.006 mg/kg (ELISA result) which was consistent with 0.072 ± 0.007 mg/kg obtained by LC-MS. The developed immunoassay method is an effective tool for environment contamination monitoring.

Glycerol Monolaurate to Ameliorate Efficacy of Inactivated Pseudorabies Vaccine.

The present study is aimed to evaluate the effect of glycerol monolaurate (GML) on the growth performance and immune enhancement of pseudorabies virus (PRV)-inactivated vaccine in the early-weaned piglets. One hundred and twenty-five 28-day-old weaned piglets were randomly assigned to a control group (CON, no vaccine and no challenge), challenge control group (C-CON), inactivated PRV vaccine group (IPV), IPV + 500 mg/kg GML group (L-GML), and IPV + 1,000 mg/kg GML group (H-GML) during the entire 28-day experimental period. All the data analyses were performed by one-way analysis of variance (ANOVA) and multiple comparisons. Our results showed that the final weight, average daily gain (ADG), and average daily feed intake (ADFI) of H-GML were the highest in each group, and F/G of H-GML was increased but there was no significant difference with CON (p > 0.05). Levels of PRV glycoprotein B (gB) antibody and immunoglobulin in serum of L-GML and H-GML were higher than those of IPV, but only gB antibody levels and immunoglobulin G (IgG) in H-GML were significantly increased (p < 0.05). Compared with IPV, the contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in serum of L-GML (TNF-α and IL-1ß: p > 0.05, IL-6: p < 0.05, respectively) and H-GML (p < 0.01, both) were all decreased, and the content of interleukin-10 (IL-10) in H-GML was increased (p > 0.05). Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) experiments proved that L-GML and H-GML were both superior to IPV in inhibiting the expression of TNF-α (p < 0.01), IL-6 (p > 0.05), and IL-1ß (p < 0.01) mRNAs and promoting the expression of IL-10 mRNA (L-GML: p > 0.05, H-GML: p < 0.05, respectively) in the superficial inguinal lymph nodes. Histopathological examination found mild congestion in the lung and inguinal lymph nodes of IPV, while the tissues (brain, lung, and inguinal lymph nodes) of L-GML and H-GML were the same as CON with no obvious lesions. The above results indicate that GML may improve the growth performance of weaned piglets and enhance the immunity of PRV-inactivated vaccine by increasing the levels of PRV gB antibody and immunoglobulin and regulating cytokine levels.

Genome-wide identification of bHLH transcription factors: Discovery of a candidate regulator related to flavonoid biosynthesis in Erigeron breviscapus.

Erigeron breviscapus is a Compositae plant, and its rich flavonoids have shown strong preventative and curative effects in the treatment of cardio- and cerebrovascular diseases. bHLH genes play a crucial role in plant growth and development. There are 116 EbbHLH genes in E. breviscapus, and each gene has been named based on its chromosome location. Our phylogenetic analysis divided these genes into 18 subfamilies. To further investigate its function, EbbHLH80 was isolated from E. breviscapus leaves. Next, transcriptomic and metabolomic analyses of tobacco leaves were performed. Among 421 differentially accumulated compounds, 98 flavonoids were identified. In addition, differentially expressed genes were identified using RNA-seq, and further analysis suggested that EbbHLH80-OE could not only regulate the expression of some structural genes in the flavonoid biosynthesis pathway to achieve flavonoid accumulation but also be involved in the regulation of a series of downstream pathways, such as stress response, ABA and ethylene signal transduction, to affect plant growth and development. The results of our analysis provide new insights into the function of EbbHLH80 and lay the foundation for future functional studies on E. breviscapus.

EbMYBP1, a R2R3-MYB transcription factor, promotes flavonoid biosynthesis in Erigeron breviscapus.

Erigeron breviscapus, a traditional Chinese medicinal plant, is enriched in flavonoids that are beneficial to human health. While we know that R2R3-MYB transcription factors (TFs) are crucial to flavonoid pathway, the transcriptional regulation of flavonoid biosynthesis in E. breviscapus has not been fully elucidated. Here, EbMYBP1, a R2R3-MYB transcription factor, was uncovered as a regulator involved in the regulation of flavonoid accumulation. Transcriptome and metabolome analysis revealed that a large group of genes related to flavonoid biosynthesis were significantly changed, accompanied by significantly increased concentrations of the flavonoid in EbMYBP1-OE transgenic tobacco compared with the wild-type (WT). In vitro and in vivo investigations showed that EbMYBP1 participated in flavonoid biosynthesis, acting as a nucleus-localized transcriptional activator and activating the transcription of flavonoid-associated genes like FLS, F3H, CHS, and CHI by directly binding to their promoters. Collectively, these new findings are advancing our understanding of the transcriptional regulation that modulates the flavonoid biosynthesis.

Perfluorooctanoic acid and perfluorooctane sulfonic acid inhibit plant growth through the modulation of phytohormone signalling pathways: Evidence from molecular and genetic analysis in Arabidopsis.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are the most representative perfluoroalkyl substances that accumulate in the food chain and are harmful to the environment. The uptake, translocation and physiological effects of PFOA and PFOS in plants have been reported in recent years; however, the regulatory mechanisms underlying PFOA- and PFOS-mediated plant growth and development remain largely unclear. Here, using Arabidopsis thaliana as the study material, we showed that both PFOA and PFOS inhibited plant growth; PFOS showed a stronger inhibitory effect on primary root (PR) growth, whereas PFOA exerted a stronger inhibitory effect on photosynthesis. Transcriptome analysis revealed that PFOA- and PFOS-modulated plant growth and development were correlated with the phytohormones auxin and abscisic acid (ABA). Further genetic analyses using mutants related to auxin biosynthesis, receptors and transport and mutants related to ABA biosynthesis and signalling transduction revealed that both PFOA and PFOS inhibited PR growth by modulating auxin biosynthesis and signalling pathways, and the ABA signalling pathway was also involved in PFOS-mediated PR growth inhibition. Collectively, these results shed new light on the molecular mechanisms of PFOA- and PFOS-mediated root system growth and their effects on phytohormone signalling pathways in plants.

Same Dosages of rPRV/XJ5-gI-/gE-/TK- Prototype Vaccine or Bartha-K61 Vaccine Similarly Protects Growing Pigs Against Lethal Challenge of Emerging vPRV/XJ-5 Strain.

Variant pseudorabies viruses (vPRV) have constantly emerged in China since late 2011. In the present study, a 1 × 106.0 TCID50 per-animal dosage of a commercially available Bartha-K61 vaccine and an rPRV/XJ5-gI-/gE-/TK- prototype vaccine freshly extracted from the vPRV/XJ-5 at the same dose were administered to evaluate the immune effectiveness thereof on growing pigs to prevent lethal strikes caused by vPRV/XJ-5. The results suggest that the Bartha-K61 vaccine at a dose of 1 × 106.0 TCID50 per animal and the same dosage of the rPRV/XJ5-gI-/gE-/TK- prototype vaccine protected growing pigs against the lethal challenge of vPRV/XJ-5 strain with 100% survive rate. Furthermore, the outcome of the clinical score, virus shedding, weight gain, and viral loads in different pig tissues in these two groups demonstrates that either the Bartha-K61 vaccine or the rPRV/XJ5-gI-/gE-/TK- prototype vaccine at the same dose exhibited parallel efficacy in pigs against the lethal challenge with the XJ-5 strain of vPRV.

Effectiveness of Postoperative Radiotherapy in Patients with Atypical Meningiomas After Gross Total Resection: Analysis of 260 Cases.

OBJECTIVE: It remains controversial whether patients with atypical meningiomas can benefit from postoperative radiotherapy (PORT) after gross total resection (GTR). This study aimed to explore the effectiveness of PORT in patients with atypical meningiomas after GTR based on our single-center data with a relatively large sample size. METHODS: Patients with atypical meningiomas who underwent GTR in our center were reviewed. Univariable and multivariable Cox proportional hazard models were conducted for survival analyses. Kaplan-Meier survival curves were generated, and 5-year progression-free survival (PFS) rates were calculated. RESULTS: This study enrolled 260 patients. PORT was not associated with PFS (P = 0.507). Sex (P = 0.006, hazard ratio 0.418, 95% confidence interval 0.224-0.781), age (P = 0.032, hazard ratio 1.032, 95% confidence interval 1.003-1.061), and tumor location (P = 0.026, hazard ratio 0.199, 95% confidence interval 0.048-0.824) were independent predictors of PFS. The 5-year PFS rate of patients receiving PORT (85.6%) was similar to that of patients not receiving PORT (84.8%). The 5-year PFS rate was 100% in patients with convexity atypical meningiomas regardless of whether or not they received PORT. CONCLUSIONS: PORT after GTR may not prolong PFS in patients with atypical meningiomas. Patients with convexity atypical meningiomas had favorable outcomes after GTR regardless of receipt of PORT.

An Inter-Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer.

Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell-mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor-homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor-targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4-granzyme B-dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter-supplementary biohybrid system.