Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

An efficient electrochemical sensor based on the Ce-MOF/g-C3N5 composite for the detection of nitrofurazone.

The Ce-MOF/g-C3N5 composite was first constructed using a simple reflux method in an oil bath. Herein, we report that the electrochemical sensor fabricated based on this composite exhibits high performance in the detection of nitrofurazone. Interestingly, this sensor exhibits an extra-wide linear range of detection composed of two line segments (7-100 µM and 100-2913 µM), as well as a low detection limit (LOD) of 6.15 µM (S/N = 3) under optimal experimental conditions. Additionally, the sensor demonstrates exceptional selectivity, reproducibility and stability. More importantly, the proposed electrochemical sensor can effectively monitor nitrofurazone in real samples such as urea and tap water, and obtain ideal recoveries. The sensor has such excellent performance because of the synergistic effect of the two components in the Ce-MOF/g-C3N5 composite. Compared with Ce-MOF, the introduction of g-C3N5 effectively not only enhances the conductivity of Ce-MOF/g-C3N5 but also exposes more active sites, which is conducive to increasing the electrocatalytic activity to reduce nitrofurazone. This research contributes new scientific research ideas for fabricating ideal electrochemical sensors based on g-C3N5 and MOFs.

Tempol alleviates acute lung injury by affecting glutathione synthesis through Nrf2 and inhibiting ferroptosis in lung epithelial cells.

As a life-threatening disease, acute lung injury (ALI) may progress to chronic pulmonary fibrosis. For the treatment of lung injury, Tempol is a superoxide dismutase mimetic and intracellular redox agent that can be a potential drug. This study investigated the regulatory mechanism of Tempol in the treatment of ALI. A mouse model of ALI was established, and HE staining was used to examine histomorphology. The CCK-8 assay was used to measure cell viability, and oxidative stress was assessed by corresponding kits. Flow cytometry and dichlorodihydrofluorescein diacetate staining assays were used to detect reactive oxygen species (ROS) levels. Protein expression levels were measured by Western blot analysis and ELISA. Pulmonary vascular permeability was used to measure the lung wet/dry weight ratio. The level of oxidative stress was increased in ALI mice, and the level of ferroptosis was upregulated. Tempol inhibited this effect and alleviated ALI. The administration of Tempol alleviated the pathological changes in ALI, inhibited pulmonary vascular permeability, and improved lung injury in ALI mice. The upregulation of genes essential for glutathione (GSH) metabolism induced by lipopolysaccharide (LPS) was inhibited by Tempol. In addition, nuclear factor-related factor 2 (Nrf2) is activated by Tempol therapy to regulate the de novo synthesis pathway of GSH, thereby alleviating LPS-induced lung epithelial cell damage. The results showed that Tempol alleviated ALI by activating the Nrf2 pathway to inhibit oxidative stress and ferroptosis in lung epithelial cells. In conclusion, this study demonstrates that Tempol alleviates ALI by inhibiting ferroptosis in lung epithelial cells through the effect of Nrf2 on GSH synthesis.

Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

Chronic intermittent hypoxia-induced oxidative stress activates TRB3 and phosphorylated JNK to mediate insulin resistance and cell apoptosis in the pancreas.

This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four- and eight-week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4-week CIH, 4-week CIH-Tempol, 8-week CIH, 8-week CIH-Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8-hidroxy-2-deoxyguanosine (8-OHdG), tribbles homologue 3 (TRB3), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), insulin receptor substrate-1 (IRS-1), phosphorylated IRS-1 (Ser307) (p-IRS-1ser307 ), protein kinase B (AKT), phosphorylated AKT (Ser473) (p-AKTser473 ), B cell lymphoma protein-2 (Bcl-2), cleaved-caspase-3 (Cl-caspase-3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH-Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA-IR) and apoptosis of islet cells was increased in the CIH groups. CIH-induced oxidative stress increased the expression of p-IRS-1Ser307 and decreased the expression of p-AKTSer473 . The expression levels of TRB3 and p-JNK were higher in the CIH groups than in both the CIH-Tempol and NC groups. Meanwhile, the expressions of Cl-caspase-3 and Bcl-2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH-induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p-JNK.

Isolation and Characterization of Antimicrobial Metabolites from the Sophora tonkinensis-Associated Fungus Penicillium sp. GDGJ-N37.

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3-6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.

Pulmonary Adenoid Cystic Carcinoma Mimicking Asthma-Like Symptoms: A Case Report and Literature Review.

Introduction: Pulmonary adenoid cystic carcinoma (PACC) is a rare, low-grade malignant salivary gland-type tumor characterized by a dormant onset and slow progression, often leading to misdiagnosis. Due to its rarity, limited cases have been reported in the literature. This report aimed to enhance clinicians' understanding of this infrequent disease. Case Presentation: We present the case of a 41-year-old female patient diagnosed with PACC. Our report provides a comprehensive analysis of the patient's imaging, pathology, and treatment, with a particular focus on immunohistochemical results. Importantly, we emphasize the significance of considering foreign bodies and tumors in the bronchus when encountering asthma-like symptoms unresponsive to conventional treatments. Due to the uncertain etiology and pathophysiology of PACC, there are currently no established guidelines for chemotherapy and radiotherapy. Conclusion: PACC predominantly manifests as bronchial lesions without significant clinical heterogeneity. Therefore, it is crucial to consider foreign bodies and tumors in the bronchus when dealing with asthma-like symptoms, especially in patients without chronic lung disease who do not respond to anti-infective, antispasmodic, and antiasthmatic treatments. Additionally, meticulous examination of lesions is essential for timely diagnosis and intervention, ultimately improving patient survival rates.

4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) alleviates lung injury by inhibiting SIRT6-HIF-1α signaling pathway activation through the upregulation of miR-212-5p expression.

OBJECTIVE: Obstructive sleep apnea is closely related to oxidative stress. 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) can scavenge reactive oxygen species (ROS) and ameliorate oxidative damage in the body. The mechanism by which Tempol alleviates chronic intermittent hypoxia-induced lung injury has rarely been reported. This study aimed to confirm the molecular mechanism by which Tempol alleviates lung injury. METHODS: The levels of miR-212-5p and Sirtuin 6 (SIRT6) in injured lungs were analyzed using bioinformatics. In vitro, intermittent hypoxia (IH) treatment induced hypoxia in BEAS-2B cells and we established a model of chronic intermittent hypoxia (CIH) in mouse using a programmed hypoxia chamber. We used HE staining to observe the morphology of lung tissue, and the changes in lung fibers were observed by Masson staining. The levels of inflammatory factors in mouse serum were detected by ELISA, and the levels of the oxidative stress indicators GSH, MDA, SOD and ROS were detected using commercially available kits. Moreover, a real-time qPCR assay was used to detect miR-212-5p expression, and Western blotting was used to detect the levels of SIRT6, HIF-1α and apoptosis-related proteins. CCK-8 was used to detect cell proliferation. Subsequently, we used flow cytometry to detect cell apoptosis. Dual-luciferase gene reporters determine the on-target binding relationship of miR-212-5p and SIRT6. RESULTS: SIRT6 was highly expressed in CIH-induced lung injury, as shown by bioinformatics analysis; however, miR-212-5p expression was decreased. Tempol promoted miR-212-5p expression, and the levels of SIRT6 and HIF-1α were inhibited. In BEAS-2B cells, Tempol also increased proliferation, inhibited apoptosis and inhibited oxidative stress in BEAS-2B cells under IH conditions. In BEAS-2B cells, these effects of Tempol were reversed after transfection with an miR-212-5p inhibitor. miR-212-5p targeted and negatively regulated the level of SIRT6 and overexpression of SIRT6 effectively reversed the enhanced influence of the miR-212-5p mimic on Tempol's antioxidant activity. Tempol effectively ameliorated lung injury in CIH mice and inhibited collagen deposition and inflammatory cell infiltration. Likewise, the therapeutic effect of Tempol could be effectively reversed by interference with the miR-212-5p inhibitor. CONCLUSION: Inhibition of the SIRT6-HIF-1α signaling pathway could promote the effect of Tempol by upregulating the level of miR-212-5p, thereby alleviating the occurrence of lung injury and providing a new underlying target for the treatment of lung injury.

Effect of Preoperative Nutritional Status on Postoperative Functional Recovery of Hip Joint in Elderly Patients with Intertrochanteric Fractures.

Objective: The state of nutrition of senior patients with intertrochanteric fracture of femur before operation affects the patients' tolerance to the operation,the body recovery, healing of the wound and clinical prognosis. For these patients, the poor state of nutrition may lengthen the time of being in hospital, leading to poor hip recovery and clinical outcome. But currently, the relationship between functional recovery of hip joint after operation of intertrochanteric fracture in elderly patients and camp condition has not been reported. To investigate the effect of preoperative nutritional status on postoperative recovery of hip joint function in elderly patients with intertrochanteric fractures. Methods: Retrospective analysis was performed on the data of 96 elderly patients with intertrochanteric fracture of the femur treated with closed reduction PFNAfrom January 2021 to January 2022 in Dongying People's Hospital Trauma Orthopedics Department. There were 36 male patients and 60 female patients aged from 65 to 92.The patients were divided into the normal nutrition group (GNRI ≥ 92, n = 46) and the malnutrition group (GNRI < 92, n = 50). The general clinical data, time from injury to operation, intraoperative and postoperative allogeneic blood transfusion rate, postoperative complication rate, postoperative mortality 1 year, and Harris hip function score at 3, 6, 9 months and the last follow-up were compared between the two groups. Results: All patients were followed up for 9 to 15 months(mean,13.9 months) after surgery. The preoperative hemoglobin levels in the normal and malnutrition groups were 8.6-13.2 and 7.4-11.2 g/dL, respectively (P < .05). The time from injury to surgery in the normal nutrition group was significantly shorter than that in the malnutrition group (P < .01). The preoperative hemoglobin level in the normal nutrition group was significantly higher than that in the malnutrition group. The time from injury to operation in normal nutrition group and malnutrition group are respectively (1.1-5.2), (4.3-6.6)d; the intraoperative and postoperative allogeneic blood transfusion rates are respectively 47.8%(22/46), 92%(46/50);the incidence of postoperative complications are respectively 6.52%(3/46), 32%(16/50); the mortality rates within 1 year after operation are respectively 2.17%(1/46), 12%(6/50). In contrast, the postoperative allogeneic blood transfusion, postoperative complication, and postoperative complication rates in the normal nutrition group were significantly lower than those in the malnutrition group (P < .05). 3 months after surgery, the Harris hip function scores of patients in normal nutrition group and malnutrition group are respectively (75.26±4.02), (64.28±3.82); 6 months after surgery, the Harris hip function scores of them are respectively (80.42±3.86), (70.14±5.06).During the last follow-up, scores are (82.23±2.98), (72.12±4.62). At the 3, 6, and last follow-up after surgery, the Harris hip function score in the normal nutrition group was significantly higher than in the malnutrition group (P < .05). Conclusion: Preoperative malnutrition in elderly patients with intertrochanteric fracture has adverse effects on postoperative hip function recovery, and 1-year postoperative survival rate.GNRI can be used for simple screening. Early assessment of patients' nutritional status.

The Patent Landscape of mTOR and PTEN Targets.

BACKGROUND: PTEN and mTOR signaling have many roles, including antiinflammatory, immunosuppressant and cancer. OBJECTIVE: US patents were retrieved to show the current landscape of the mTOR and PTEN targets. METHODS: PTEN and mTOR targets were analyzed by patent analysis. The U.S. granted patents from January 2003 to July 2022 were performed and analyzed. RESULTS: The results showed that the mTOR target was more attractive in drug discovery than the PTEN target. Our findings indicated that most large global pharmaceutical companies focused the drug discovery related to the mTOR target. The present study demonstrated that mTOR and PTEN targets showed more applications in biological approaches compared to BRAF and KRAS targets. The chemical structures of the inhibitors of the mTOR target demonstrated some similar features to those of the inhibitors of KRAS targets. CONCLUSION: At this stage, the PTEN target may not be an ideal target subjected to new drug discovery. The present study was the first one which demonstrated that the group of O=S=O may play a critical role in the chemical structures of mTOR inhibitors. It was the first time to show that a PTEN target may be suitably subjected to new therapeutic discovery efforts related to biological applications. Our findings provide a recent insight into therapeutic development for mTOR and PTEN targets.

Comparative Analysis of Therapeutic Outcomes and Prognoses Among Osteoporosis Patients with Varied Bone Mineral Density T-Values Following Percutaneous Kyphoplasty.

Objective: This study aims to evaluate and compare the therapeutic outcomes and prognoses of osteoporotic fracture (OSF) patients undergoing percutaneous kyphoplasty (PKP), emphasizing the role of bone mineral density T-values (BMD-T) as a guiding factor in the surgical intervention for OSF. Methods: An observational cohort study was conducted, and 162 OSF patients admitted to our hospital from March 2021 to December 2021 were selected. Patients were categorized based on BMD-T into mild (-2.5 ≤ BMD-T ≤ -4, n=40), moderate (-4 < BMD-T ≤ -5, n = 78), and severe groups (BMD-T < -5, n = 44). All patients underwent PKP treatment, and vertebral body (VB) lavage fluid was analyzed for calcium (Ca), magnesium (Mg), and zinc (Zn) levels. X-ray assessments were performed before and after surgery to examine changes in wedge and kyphosis angles and VB height. Additionally, the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), and Barthel Index (BI) scores were recorded. Results: The mild group exhibited the highest Ca, Mg, and Zn contents in VB lavage fluid, while the severe group had the lowest (P < .05). A positive correlation was observed between patients' Ca, Mg, and Zn levels and BMD-T (P < .05). The severe group, characterized by lower BMD-T, required a higher amount of bone cement injection, resulting in more significant differences in wedge angle, kyphosis angle, and VB height before and after surgery (P < .05). Moreover, the severe group demonstrated a higher incidence of postoperative adverse reactions (P < .05). Age, bone cement leakage, BMD-T, Ca, Mg, and Zn were identified as independent factors influencing post-PKP re-fracture in OSF patients (P < .05). Conclusion: In PKP for OSF, lower BMD-T correlates with improved correction but is also associated with a higher likelihood of cement leakage.

Tempol attenuates chronic intermittent hypoxia-induced lung injury through the miR-145-5p/Nrf2 signaling pathway.

This study mainly explored the effect of Tempol on OSA-induced lung injury and the specific molecular mechanism. A hypoxia/reoxygenation (H/R) cell model and an IH-induced lung injury model in rats were constructed. The expression of miRNAs and related proteins was detected by RT‒qPCR and Western blotting. HE and Masson staining were used to observe the pathological changes in lung tissues. The expression levels of inflammatory cytokines were detected by ELISA. Apoptotic cells were observed by TUNEL. The ROS levels were detected by a DCFH-DA probe. Tempol administration effectively reduced the pathological changes in lung tissue and the progression of pulmonary fibrosis in rats with lung injury and reduced the expression of inflammatory factors in lung tissue. miR-145-5p was significantly upregulated in rats with IH-induced lung injury, and Tempol treatment inhibited the expression of miR-145-5p. Transfection with the miR-145-5p inhibitor effectively inhibited H/R cell apoptosis and autophagy, while transfection with the miR-145-5p mimic had the opposite effect. Targeting miR-145-5p negatively regulates the expression of Nrf2. Transfection of the miR-145-5p mimic weakened the inhibitory effects of Tempol on apoptosis and autophagy in H/R cells. Overexpression of the Nrf2 mimic reversed the effects of the miR-145-5p mimic on Tempol to a certain extent. It was also confirmed in animal experiments that overexpression of Nrf2 reversed the inhibitory effect of the miR-145-5p mimic on Tempol's lung injury relief effect. Tempol alleviates lung injury induced by chronic interstitial hypoxia by regulating the miR-145-5p/Nrf2 molecular axis and inhibiting autophagy.

Analysis of DNA Methylation Differences during the JIII Formation of Bursaphelenchus xylophilus.

DNA methylation is a pivotal process that regulates gene expression and facilitates rapid adaptation to challenging environments. The pinewood nematode (PWN; Bursaphelenchus xylophilus), the causative agent of pine wilt disease, survives at low temperatures through third-stage dispersal juvenile, making it a major pathogen for pines in Asia. To comprehend the impact of DNA methylation on the formation and environmental adaptation of third-stage dispersal juvenile, we conducted whole-genome bisulfite sequencing and transcriptional sequencing on both the third-stage dispersal juvenile and three other propagative juvenile stages of PWN. Our findings revealed that the average methylation rate of cytosine in the samples ranged from 0.89% to 0.99%. Moreover, we observed significant DNA methylation changes in the third-stage dispersal juvenile and the second-stage propagative juvenile of PWN, including differentially methylated cytosine (DMCs, n = 435) and regions (DMRs, n = 72). In the joint analysis of methylation-associated transcription, we observed that 23 genes exhibited overlap between differentially methylated regions and differential gene expression during the formation of the third-stage dispersal juvenile of PWN. Further functional analysis of these genes revealed enrichment in processes related to lipid metabolism and fatty acid synthesis. These findings emphasize the significance of DNA methylation in the development of third-stage dispersal juvenile of PWN, as it regulates transcription to enhance the probability of rapid expansion in PWN.

Engineered pine endophytic Bacillus toyonensis with nematocidal and colonization abilities for pine wilt disease control.

Introduction: The pinewood nematode (PWN) is responsible for causing pine wilt disease (PWD), which has led to the significant decline of conifer species in Eurasian forests and has become a globally invasive quarantine pest. Manipulating plant-associated microbes to control nematodes is an important strategy for sustainable pest management. However, it has proven difficult to find pine-associated bacteria that possess both nematocidal activity and the ability to colonize pine tissues. Methods: The stress experiments with turpentine and pine tissue extract were carried out to screen for the desired target strain that could adapt to the internal environment of pine trees. This strain was used to construct an engineered nematocidal strain. Additionally, a fluorescent strain was constructed to determine its dispersal ability in Pinus massoniana seedlings through plate separation, PCR detection, and fluorescence microscopy observations. The engineered nematocidal strain was tested in the greenhouse experiment to assess its ability to effectively protect P. massoniana seedlings from nematode infection. Results: This study isolated a Bacillus toyonensis strain Bxy19 from the healthy pine stem, which showed exceptional tolerance in stress experiments. An engineered nematocidal strain Bxy19P3C6 was constructed, which expressed the Cry6Aa crystal protein and exhibited nematocidal activity. The fluorescent strain Bxy19GFP was also constructed and used to test its dispersal ability. It was observed to enter the needles of the seedlings through the stomata and colonize the vascular bundle after being sprayed on the seedlings. The strain was observed to colonize and spread in the tracheid after being injected into the stems. The strain could colonize the seedlings and persist for at least 50 days. Furthermore, the greenhouse experiments indicated that both spraying and injecting the engineered strain Bxy19P3C6 had considerable efficacy against nematode infection. Discussion: The evidence of the colonization ability and persistence of the strain in pine advances our understanding of the control and prediction of the colonization of exogenously delivered bacteria in pines. This study provides a promising approach for manipulating plant-associated bacteria and using Bt protein to control nematodes.

Transcriptomic response of Pinus massoniana to infection stress from the pine wood nematode Bursaphelenchus xylophilus.

The pinewood nematode (PWN) Bursaphelenchus xylophilus is a forestry quarantine pest and causes an extremely dangerous forest disease that is spreading worldwide. Due to the complex pathogenic factors of pine wood nematode disease, the pathogenesis is still unknown. B. xylophilus ultimately invades a host and causes death. However, little is known about the defence-regulating process of host pine after infection by B. xylophilus at the molecular level. Therefore, we wanted to understand how Pinus massoniana regulates its response to invasion by B. xylophilus. P. massoniana were artificially inoculated with B. xylophilus solution, while those without B. xylophilus solution were used as controls. P. massoniana inoculated with B. xylophilus solution for 0 h, 6 h, 24 h, and 120 h was subjected to high-throughput sequencing to obtain transcriptome data. At various time points (0 h, 6 h, 24 h, 120 h), gene transcription was measured in P. massoniana inoculated with PWN. At different time points, P. massoniana gene transcription differed significantly, with a response to early invasion by PWN. According to Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, P. massoniana response to PWN invasion involves a wide range of genes, including plant hormone signal transformation, flavonoid biosynthesis, amino sugar and nucleoside sugar metabolism, and MAPK signalling pathways. Among them, inoculation for 120 hours had the greatest impact on differential genes. Subsequently, weighted gene coexpression network analysis (WGCNA) was used to analyse transcriptional regulation of P. massoniana after PWN infection. The results showed that the core gene module of P. massoniana responding to PWN was "MEmagenta", enriched in oxidative phosphorylation, amino sugar and nucleotide sugar metabolism, and the MAPK signalling pathway. MYB family transcription factors with the highest number of changes between infected and healthy pine trees accounted for 20.4% of the total differentially expressed transcription factors. To conclude, this study contributes to our understanding of the molecular mechanism of initial PWN infection of P. massoniana. Moreover, it provides some important background information on PWN pathogenic mechanisms.

DNA methylation on C5-Cytosine and N6-Adenine in the Bursaphelenchus xylophilus genome.

BACKGROUND: The pinewood nematode is the causal agent of the pine wilt disease, which causes severe ecological and economic losses in coniferous forests. The invasion of pine wood nematode has undergone various rapid adaptations to a wide range of temperatures and to new hosts and vector insects. DNA methylation may play crucial roles in the rapid adaptation of PWN during invasion. However, whether the PWN genome contins functional DNA modifications remains elusive. RESULTS: Here, we detected the extensive presence of 5-methylcytosine (5mC) and N6-methyladenine (6mA) in the B. xylophilus genome, with low methylation levels at most positions. Cytosines were methylated in the CpG, CHG. and CHH sequence contexts, with the lowest methylation levels at CpG sites. The methylation levels of CpG and 6mA in gene regions showed opposite trends. The changes in the abundance of 5mC and 6mA showed the same trends in response to temperature change, but opposite trends during development. Sequence and phylogenetic analyses showed that the proteins BxDAMT and BxNMAD have typical characteristics of a methylase and demethylase, respectively, and are conserved among species. CONCLUSIONS: These findings shed light on the epigenetic modifications present in the genome of PWN, and will improve our understanding of its invasiveness and evolution.

Global diversity and biogeography of potential phytopathogenic fungi in a changing world.

Phytopathogenic fungi threaten global food security but the ecological drivers of their global diversity and biogeography remain unknown. Here, we construct and analyse a global atlas of potential phytopathogenic fungi from 20,312 samples across all continents and major oceanic island regions, eleven land cover types, and twelve habitat types. We show a peak in the diversity of phytopathogenic fungi in mid-latitude regions, in contrast to the latitudinal diversity gradients observed in aboveground organisms. Our study identifies climate as an important driver of the global distribution of phytopathogenic fungi, and our models suggest that their diversity and invasion potential will increase globally by 2100. Importantly, phytopathogen diversity will increase largely in forest (37.27-79.12%) and cropland (34.93-82.51%) ecosystems, and this becomes more pronounced under fossil-fuelled industry dependent future scenarios. Thus, we recommend improved biomonitoring in forests and croplands, and optimised sustainable development approaches to reduce potential threats from phytopathogenic fungi.

Antibacterial and Antimalarial Therapeutic Agents: A Patent Perspective.

BACKGROUND: Antibacterial and antimalarial drugs play a critical role in combating infectious diseases. It is a continuous work to develop new types of antibacterial and antimalarial drugs. OBJECTIVES: To better understand current landscape and association of antibacterial and antimalarial agents, the European patent analysis was performed. METHODS: Antibacterial and antimalarial agents were analyzed by patent analysis. Patent documents from January 2003 to May 2022 were retrieved and analyzed. RESULTS: The present study indicated there were virtually three therapeutic approaches for antibacterial agents, including chemical drugs, biological products and siRNA technology. Chemical drugs were a mainstream therapeutic approach for development of both antibacterial and antimalarial agents. However, the present study found that in contrast to antimalarials, siRNA technology had been initially explored as therapeutic strategy for antibacterial agents. Also, our study is the first to show that there is a low correlation between antibacterial and antimalarial agents. CONCLUSION: Globally, our study is the first one to show that it may be not a fast approach to discover antimalarial drugs from antibacterial agents based on drug repurposing. siRNA technology as therapeutic strategy had been explored and used in antibacterial field.

To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer based on network pharmacology combined with LC-MS.

OBJECTIVE: To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology and LC-MS technology. METHODS: The effective components in Maiwei Dihuang decoction were detected by liquid chromatography-mass spectrometry (LC-MS). Use the SuperPred database to collect the relevant targets of the active ingredients of Mai Wei Di Tang, and then collect the relevant targets of non-small cell lung cancer from GeneCards, DisgenNET and OMIM databases. On this basis, PPI network construction, GO enrichment analysis and KEGG pathway annotation analysis were carried out for target sites. Finally, AutoDock Vina is used for molecular docking. RESULTS: We further screened 16 effective Chinese herbal compounds through LC-MS combined with ADME level. On this basis, we obtained 77 core targets through protein interaction network analysis. Through GO, KEGG analysis and molecular docking results, we finally screened out the potential targets of Maiwei Dihuang Decoction for NSCLC: TP53, STAT3, MAPK3. CONCLUSION: Maiwei Dihuang decoction may play a role in the treatment of NSCLC by co-regulating TP53/STAT3/MAPK3 signal pathway.

Ternary XBe4H5- (X = Si, Ge, Sn, Pb) Clusters: Planar Tetracoordinate Si/Ge/Sn/Pb Species with 18 Valence Electrons.

As one of the important probes of chemical bonding, planar tetracoordinate carbon (ptC) compounds have been receiving much attention. Compared with ptC clusters, the heavier planar tetracoordinate silicon, germanium, tin, lead (ptSi/Ge/Sn/Pb) systems are scarcer and more exotic. The 18-valence-electron (ve)-counting is one important guide, though not the only rule, for the design of planar tetra-, penta-coordinate carbon and silicon clusters. The 18ve ptSi/Ge system is very scarce and needs to be expanded. Based on the isoelectronic principle and bonding similarity between the Al atom and the BeH unit, inspired by the previously reported ptSi global minimum (GM) SiAl42-, a series of ternary 18 ve XBe4H5- (X = Si, Ge, Sn, Pb) clusters were predicted with the ptSi/Ge/Sn/Pb centers. Extensive density functional theory (DFT) global minimum searches and high-level CCSD(T) calculations performed herein indicated that these ptSi/Ge/Sn/Pb XBe4H5- (X = Si, Ge, Sn, Pb) clusters were all true GMs on their potential energy surfaces. These GMs of XBe4H5- (X = Si, Ge, Sn, Pb) species possessed the beautiful fan-shaped structures: XBe4 unit can be stabilized by three peripheries bridging H and two terminal H atoms. It should be noted that XBe4H5- (X = Si, Ge, Sn, Pb) were the first ternary 18 ve ptSi/Ge/Sn/Pb species. The natural bond orbital (NBO), canonical molecular orbitals (CMOs) and adaptive natural densitpartitioning (AdNDP) analyses indicated that 18ve are ideal for these ptX clusters: delocalized one π and three σ bonds for the XBe4 core, three Be-H-Be 3c-2e and two Be-H σ bonds for the periphery. Additionally, 2π plus 6σ double aromaticity was found to be crucial for the stability of the ptX XBe4H5- (X = Si, Ge, Sn, Pb) clusters. The simulated photoelectron spectra of XBe4H5- (X = Si, Ge, Sn, Pb) clusters will provide theoretical basis for further experimental characterization.