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Abstract. Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A ‘disease in a dish’ can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, ‘-omics’ analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.

The synergistic interaction between emergency management departments and enterprises constitutes a fundamental mechanism for mitigating the risks of technological accidents caused by natural disasters (Natech). The efficacy of this collaborative approach is impacted by comprehensive risk analyses and the game between government and enterprise. Predicated on these premises, the evolutionary game analysis of government–enterprise collaboration in coping with Natech risk was carried out. Firstly, an evolutionary game model of government–enterprise collaboration in coping with Natech risk was constructed. Secondly, the evolutionary stability strategy (ESS) was developed. Finally, these strategies were substantiated through numerical simulations. The findings revealed that at lower levels of Natech risk, enterprises will choose low investment in coping capacity building, and emergency management departments will choose delayed disposal. Under moderate Natech risk, enterprises will increase their investments if emergency management departments persist with delayed strategies, and emergency management departments will react proactively if enterprises persist with low investment. Under a high Natech risk, a pattern of strategic misalignment emerges between the two entities. This study contributes a theoretical basis for the optimization of government–enterprise collaboration in coping with Natech risks.

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.

Bovine milk-derived exosomes (BMDEs) have emerged as a fruitful area of investigation in age-related disease therapeutics. Through the utilization of BMDEs, researchers possess the capacity to unveil novel treatments and therapeutic interventions that have the potential to enhance the quality of life for elderly individuals across the globe. Studies have provided evidence of the efficacy of BMDEs in facilitating the regenerative processes of bone and cartilage, thus establishing their potential as a viable therapeutic avenue for addressing conditions like osteoarthritis. Although BMDEs show promise as a prospective research route for tackling age-related illnesses, including Parkinson's disease, osteoporosis, and skin rejuvenation, other unanswered questions still demand more exploration. Concerns have been raised regarding the safety and efficacy of BMDEs, especially regarding their human administration, and researchers must carefully examine these concerns to identify alternatives. In conclusion, BMDEs are an area ripe for investigation into the prevention and treatment of age-related diseases.

The accident mortality rate of major accidents (MAs) show that China is still in the bottleneck period of accident prevention and control. To further promote the MAs prevention and control, this paper presents a novel major accidents evolution model from the theoretical perspective of information processing (IP). Firstly, based on the safety science paradigm of accident prevention and the emergency management paradigm of accident control, a safety information processing (SIP) process is proposed. Secondly, established the SIP model for different stages of accident prevention and control, which involves danger information processing (DIP), potential hazard information processing (PHIP), risk information processing (RIP), and emergency information processing (EIP). Thirdly, revealed the SIP of various management subject and the failure principle of accident prevention and control, that is, MAs occur under the premise of continuous failures of DIP, PHIP, RIP, and EIP under the social-technical system. Finally, the DPRE-IP model is proposed from the whole evolution path of “danger-potential hazard-risk-accident”. To demonstrate the viability of the model, this model is applied to the “6·13” Wenling major explosion accident. The results show that the proposed DPRE-IP model can provide new ideas for the formulation of accident prevention and control measures and accident analysis.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today’s mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.

In order to explore the succession of fungal community and key physicochemical properties in the fermentation process of Sichuan sun vinegar, the physicochemical properties and fungal communities of vinegar fermented grains were analyzed by national standard method and high-throughput sequencing technology. At the same time, the redundancy analysis was carried out combined with fungal community and physicochemical properties to find out the key physicochemical properties affecting the change of fungal community. The results showed that with the fermentation, the pH of vinegar fermented grains decreased, the moisture and temperature remained stable, the total acid and ammonia nitrogen content increased first and then remained stable, and the reducing sugar content increased first and then decreased. The results of high-throughput sequencing showed that there were 9 phyla and 299 genera involved in the succession of fungi during the solid-state fermentation of Sichuan sun vinegar. Pichia and Lichtheimia were the dominant fungi. Through cluster analysis, the solid-state fermentation process could be divided into three stages (the first fermentation stage, days 1~8, the second fermentation stage, days 9~12, the third fermentation stage, days 14~16). The results of redundancy analysis showed that ammonia nitrogen and total acid were the main factors affecting the fungal community. Ammonia nitrogen and total acid were negatively correlated with fermentation days 1~8, and positively correlated with the fungal community at days 9~16 of fermentation. This study revealed the diversity, succession and influencing factors of fungal communities in the solid-state fermentation process of sun vinegar, which laid the foundation for mastering the variation law of fungi in the solid-state fermentation process and the subsequent association with flavor substances.

Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies.Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms.Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.

Fermentation and aging are the key stages of flavor formation in Sichuan sun vinegar (SSV), but the generation mechanisms of the flavor produced by these processes are unknown. However, complex microbial metabolism is critical to the flavor development of SSV. In this study, we analyzed the key flavor compounds present in SSV. Combined with odor activity value (OAV), the main aroma components of SSV were screened, and the relationship between microorganisms and key flavor formation was predicted using metagenomic sequencing technology. The results revealed 38 key flavor compounds in SSV. Lactobacillus, Weissella, Acetobacter, Lichtheimia, Pediococcus, Oenococcus, Brettanomyces, Kazachstania, Pichia, Xanthomonas, Lenconostoc are widely involved in the production of key flavor compounds such as 2,3-butanediol, 2-Furanmethanol, phenylethanol, 3-(Methylthio)-1-propanol, acetic acid, lactic acid, butyric acid, isovaleric acid and other organic acids. Among them, Lichtheimia and Lactobacillus are important genera for the degradation of starch, arabinoxylan and cellulose. The acetaldehyde,4-ethyl-2-methoxy-phenol and 2-methoxy-4-methyl-phenol production pathway may be related to Lactobacillus, Acetobacter and Brettanomyces. This study provides a new understanding of the key flavor-formation stage and flavor compound generation mechanism of SSV and provides a reference for the screening and isolation of functional strains and the reconstruction of microbial communities.

With the rapid development of the autonomous driving industry, there is increasing research on related perception tasks. However, research on road surface traffic sign detection tasks is still limited. There are two main challenges to this task. First, when the target object’s pixel ratio is small, the detection accuracy often decreases. Second, the existing publicly available road surface traffic sign datasets have limited image data. To address these issues, this paper proposes a new instance segmentation network, RTS R-CNN, for road surface traffic sign detection tasks based on Mask R-CNN. The network can accurately perceive road surface traffic signs and provide important information for the autonomous driving decision-making system. Specifically, CSPDarkNet53_ECA is proposed in the feature extraction stage to enhance the performance of deep convolutional networks by increasing inter-channel interactions. Second, to improve the network’s detection accuracy for small target objects, GR-PAFPN is proposed in the feature fusion part, which uses a residual feature enhancement module (RFA) and atrous spatial pyramid pooling (ASPP) to optimize PAFPN and introduces a balanced feature pyramid module (BFP) to handle the imbalanced feature information at different resolutions. Finally, data augmentation is used to generate more data and prevent overfitting in specific scenarios. The proposed method has been tested on the open-source dataset Ceymo, achieving a Macro F1-score of 87.56%, which is 2.3% higher than the baseline method, while the inference speed reaches 23.5 FPS.

As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan–Meier method. A protein–protein interaction network was constructed using STRING software. The “ClusterProfiler” package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan–Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.

The aim of this study was to provide a practical experimental basis for the development of Neocryptotanshinone (NCTS) as an effective hypoglycemic drug and a theoretical method for the rapid screening of natural compounds with hypoglycemic effects. Molecular docking was used to screen the most suitable ligand. Hematoxylin and eosin, immunohistochemical staining, enzyme-linked immunosorbent assay and Western Blotting approved the hypoglycemic effect of NCTS. According to the free energy of binding, among 180 active compounds from the Traditional Chinese Medicine Integrated Database, NCTS was finally chose for investigation its hypoglycemic effects. In db/db mice, NCTS significantly reduced body weight and plasma glucose, improved glucose tolerance and levels of fasting plasma glucose and glycated hemoglobin A1c, and decreased insulin resistance after six-week administration. NCTS restored the pathological state in the liver of db/db mice and significantly decreased protein tyrosine phosphatase 1B (PTP1B) expression in the liver and muscle of db/db mice, which is related to the regulatory effect of NCTS on insulin receptor substrate 1. In conclusion, we successfully explored the hypoglycemic effect of NCTS in db/db mice via regulating the expression of PTP1B.

Cell-based immunotherapy using natural killer (NK) cells, cytokine-induced killer (CIK) cells and dendritic cells (DCs) is emerging as a potential novel approach in the auxiliary treatment of a tumor. However, non-standard operation procedure, small-scale cell number, or human error may limit the clinical development of cell-based immunotherapy. To simplify clinical scale NK cells, CIK cells and DCs expansions, we investigated the use of the WAVE bioreactor, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. We developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant number of cells for our adoptive cell transfer clinical protocols. The high proliferative rate, surface phenotypes, and cytotoxicity of these immune cells, as well as the safety of cultivation were analyzed to illuminate the effect of WAVE bioreactor. The results demonstrated that the benefit of utilizing modern WAVE bioreactors in cancer immunotherapy was simple, safe, and flexible production.

Abstract Background Anaplastic thyroid cancer (ATC) is one of the most aggressive of all solid tumors for which no effective therapies are currently available. Oncolytic Newcastle disease virus (NDV) has shown the potential to induce oncolytic cell death in a variety of cancer cells of diverse origins. However, whether oncolytic NDV displays antitumor effects in ATC remains to be investigated. We have previously shown that the oncolytic NDV strain FMW (NDV/FMW) induces oncolytic cell death in several cancer types. In the present study, we investigated the oncolytic effects of NDV/FMW in ATC. Methods In this study, a recombinant NDV expressing green fluorescent protein (GFP) was generated using an NDV reverse genetics system. The resulting virus was named after rFMW/GFP and the GFP expression in infected cells was demonstrated by direct fluorescence and immunoblotting. Viral replication was evaluated by end-point dilution assay in DF-1 cell lines. Oncolytic effects were examined by biochemical and morphological experiments in cultural ATC cells and in mouse models. Results rFMW/GFP replicated robustly in ATC cells as did its parent virus (NDV/FMW) while the expression of GFP protein was detected in lungs and spleen of mice intravenously injected with rFMW/GFP. We further showed that rFMW/GFP infection substantially increased early and late apoptosis in the ATC cell lines, THJ-16 T and THJ-29 T and increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage in ATC cells as assessed by immunoblotting. In addition, rFMW/GFP induced lyses of spheroids derived from ATC cells in three-dimensional (3D) cultures. We further demonstrated that rFMW/GFP infection resulted in the activation of p38 MAPK signaling, but not Erk1/2 or JNK, in THJ-16 T and THJ-29 T cells. Notably, inhibition of p38 MAPK activity by SB203580 decreased rFMW/GFP-induced cleavage of caspase-3 and PARP in THJ-16 T and THJ-29 T cells. Finally, both rFMW/GFP and its parent virus inhibited tumor growth in mice bearing THJ-16 T derived tumors. Conclusion Taken together, these data indicate that both the recombinant reporter virus rFMW/GFP and its parent virus NDV/FMW, display oncolytic activities in ATC cells in vitro and in vivo and suggest that oncolytic NDV may have potential as a novel therapeutic strategy for ATC.

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. Here, we report the genome sequence of C. sojina, and comparative genome analysis with plant pathogen members of the genus Mycosphaerella (Zymoseptoria. tritici (synonyms M. graminicola), M. pini, M. populorum and M. fijiensis - pathogens of wheat, pine, poplar and banana, respectively). Synteny or collinearity was limited between genomes of major Mycosphaerella pathogens. Comparative analysis with these related pathogen genomes indicated distinct genome-wide repeat organization features. It suggests repetitive elements might be responsible for considerable evolutionary genomic changes. These results reveal the background of genomic differences and similarities between Dothideomycete species. Wide diversity as well as conservation on genome features forms the potential genomic basis of the pathogen specialization, such as pathogenicity to woody vs. herbaceous hosts. Through comparative genome analysis among five Dothideomycete species, our results have shed light on the genome features of these related fungi species. It provides insight for understanding the genomic basis of fungal pathogenicity and disease resistance in the crop hosts.

Cell-based immunotherapy holds promise in the quest for the treatment of cancer, having potential synergy with surgery, chemotherapy and radiotherapy. As a novel approach for adoptive cell-based immunotherapy, cytokine-induced killer (CIK) cells have moved from the ‘bench to bedside’. CIK cells are a heterogeneous subset of ex-vitro expanded, polyclonal T-effector cells with both natural killer (NK) and T-cell properties, which present potent non-major histocompatibility complex-restricted cytotoxicity against a variety of tumor target cells. Initial clinical studies on CIK cell therapy have provided encouraging results and revealed synergistic antitumor effects when combined with standard therapeutic procedures. At the same time, issues such as inadequate quality control and quantity of CIK cells as well as exaggerated propaganda were continuously emerging. Thus, the Ministry of Health in China stopped CIK cell therapy in May 2016, which was a major setback for the innovation of CIK cell-based immunotherapy. Thus, it is very important to modify technical criteria to develop a standardized operation procedure (SOP) and standardized system for evaluating antitumor efficacy in a safe way.

Background: Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated.Methods: Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors.Results: Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth.Conclusions: Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.

Male infertility is a complex multifactorial disease affecting approximately 10% of couples who want to have children. Some cases of infertility can be explained by genetic factors. Septins are members of the GTPase superfamily, which are involved in diverse biological processes including morphogenesis, compartmentalization, cytokinesis, and apoptosis. The septin 12 gene, SEPT12 , is expressed exclusively in post-meiotic male germ cells and is considered as a critical gene for spermatogenesis. In this study, we evaluated 200 patients with non-obstructive azoospermia and detected mutations of 25 spermatogenesis-associated genes by targeted exome sequencing. We report a missense SEPT12 variant, c.673C>A/p.Gln225Lys, in an infertile man with non-obstructive azoospermia. The variation was located inside the GTPase domain and had a SIFT score of 0.02 (

Basil downy mildew caused by Peronospora belbahrii is a disease of sweet basil (Ocimum basilicum) production worldwide. In this study, sweet basil was grown in plant growth chambers and inoculated with sporangia of P. belbahrii harvested from previously infected plants. Plants were placed in closed, clear plastic bags and leaves harvested over time and observed using scanning electron microscopy. In most cases, sporangia germinated myceliogenically on abaxial and adaxial leaf surfaces as early as three days after inoculation. Germ tubes and the tips of hyphae ramifying on leaf surfaces directly penetrated basil leaves to initiate the infection process. Hyphal growth was not observed to gain entrance to the interior of leaves through stomata, though growth over these openings was observed. Most frequently, seven days after inoculation, one or more sporangiophores grew through stomata to produce new sporangia on both the abaxial and adaxial surfaces of leaves. Macroscopic signs of infection were visible on both sides of leaves approximately ten days after inoculation under the conditions of this study. These results contribute to a better understanding of the infection process and disease onset of P. belbahrii and should help in the development of more effective measures for reducing basil downy mildew.

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca2+ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca2+/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.

Background and objective The N-terminal truncated carboxypeptidase E (CPEΔN) protein is a novel biomarker of tumor metastasis. This study screened the H1299 cell line with a highly expressed CPEΔN gene for in vivo imaging experiment. Methods Human CPEΔN gene was cloned into the luciferase lentiviral vector. H1299 cells transduced with CPEΔN or control lentiviral vectors were selected with 2 µg/mL puromycin. The expression of CPEΔN was identified through Western blot analysis, and luciferase activity was measured using luciferase reporters. Results The human CPEΔN lentiviral expression vector was successfully constructed. The transfection rate of H1299 cells by the lentivirus achieved 80%, with an infection multiplicity of 20. The H1299 cell line with high CPEΔN (H1299-CPEΔN) expression was established, with an increase in CPEΔN expression by four times compared with the control lentivirus-transfected H1299 cell line (H1299-control). As H1299-CPEΔN and H1299-control can effectively decompose luciferase substrates, they can be applied in in vivo imaging. Conclusion H1299-CPEΔN and H1299-control can be used in in vivo imaging experiment for further research on molecular mechanisms and signal transduction to elucidate the role of CPEΔN in lung cancer metastasis.

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. The fungus Cercospora sojina is a plant pathogen that threatens global soybean supplies. Here, we report the genome sequence of C. sojina strain S9 and detect genome features and predicted genomic elements. The genome sequence of C. sojina is a valuable resource with potential in studying the fungal pathogenicity and soybean host resistance to frogeye leaf spot (FLS), which is caused by C. sojina. The C. sojina genome sequence has been deposited and available at DDBJ/EMBL/GenBank under the project accession number AHPQ00000000.

Body colours are important and striking features for individual survival and reproductive success, in particular in vertebrates where mating behaviour and mate preference may be strongly influenced by non-normal phenotypes. Pigmentation disorders may be generated by disruption of one or many independent genes as well as by environmental factors. The first discovery of albino yellow catfish (Pelteobagrus fulvidraco Richardson) with golden skin colour from fish farms in China provides us valuable material to study the molecular mechanism underlying the abnormalities of pigmentation. In this study, transcriptome sequencing of fin tissues corresponding to the distinct body colours, wild type and mutant albino yellow catfish, were performed using Illumina sequencing technology. Based on next-generation sequencing technology and de novo assembly, we generated a transcriptome of P. fulvidraco. A number of genes differentially expressed between the wild types and albinos were identified, suggesting their contribution to the different phenotypes and fitness. However, non-synonymous mutations result from single nucleotide substitutions residing in coding regions may not contribute to such differences. Based on the high-throughput expression data generated for the two different types of P. fulvidraco, we found that alterations of expression pattern may be more common than non-synonymous mutations. The transcriptome of P. fulvidraco will be an invaluable resource for subsequent comparative genomics and evolutionary analyses of this economically important fish.