Reduced circ_lrrc49 in trigeminal ganglion contributes to neuropathic pain in mice by downregulating Ist1 and impairing autophagy.

Orofacial neuropathic pain is a common symptom induced by orofacial nerve injury caused by a range of trauma or dental and maxillofacial procedures but lacks effective treatment. Circular RNAs (circRNAs) participate in the regulatory processes of neuropathic pain. Nevertheless, the biological roles of circRNAs in orofacial neuropathic pain remain unexplored. In this study, circRNA sequencing and Real-time quantitative polymerase chain reaction (RT-qPCR) were carried out. Notably, a novel circRNA named circ_lrrc49 was identified to be downregulated following chronic constriction injury of the infraorbital nerve (CCI-ION) in mice on day 14. Subsequent RNA Antisense Purification (RAP)-mass spectrometry and RNA immunoprecipitation found a direct interaction between circ_lrrc49 and increased sodium tolerance 1 homolog (Ist1). Western blot (WB) identified decreased expression of Ist1 on day 14 post-CCI-ION. Considering the known relationship between Ist1 and autophagy, LC3-II and p62 were detected to be upregulated, and an accumulation of autophagosomes were observed at the same time point. Besides, the knockdown of circ_lrrc49 by small interfering RNA (siRNA) reduced Ist1 expression, increased LC3-II, p62 levels and autophagosomes amount, and evoked orofacial mechanical hypersensitivity, which could be counteracted by the Ist1 overexpression. Similarly, the knockdown of Ist1 by siRNA also increased LC3-II and p62 levels and evoked orofacial mechanical hypersensitivity without influence on circ_lrrc49. Moreover, autophagy activation by rapamycin alleviated orofacial mechanical hypersensitivity evoked by CCI-ION or circ_lrrc49 knockdown. In conclusion, our data revealed the existence of a circ_lrrc49/Ist1/autophagy signaling axis contributing to the progression of orofacial neuropathic pain. These discoveries reveal the intricate molecular processes that drive orofacial neuropathic pain and identify circ_lrrc49 as a promising target for potential therapeutic interventions.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.

BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus. METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures. RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression. CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

Endophytes Alleviate Drought-Derived Oxidative Damage in Achnatherum inebrians Plants Through Increasing Antioxidants and Regulating Host Stress Responses.

Endophytes generally increase antioxidant contents of plants subjected to environmental stresses. However, the mechanisms by which endophytes alter the accumulation of antioxidants in plant tissues are not entirely clear. We hypothesized that, in stress situations, endophytes would simultaneously reduce oxidative damage and increase antioxidant contents of plants and that the accumulation of antioxidants would be a consequence of the endophyte ability to regulate the expression of plant antioxidant genes. We investigated the effects of the fungal endophyte Epichloë gansuensis (C.J. Li & Nan) on oxidative damage, antioxidant contents, and expression of representative genes associated with antioxidant pathways in Achnatherum inebrians (Hance) Keng plants subjected to low (15%) and high (60%) soil moisture conditions. Gene expression levels were measured using RNA-seq. As expected, the endophyte reduced the oxidative damage by 17.55% and increased the antioxidant contents by 53.14% (on average) in plants subjected to low soil moisture. In line with the accumulation of antioxidants in plant tissues, the endophyte increased the expression of most plant genes associated with the biosynthesis of antioxidants (e.g., MIOX, crtB, gpx) while it reduced the expression of plant genes related to the metabolization of antioxidants (e.g., GST, PRODH, ALDH). Our findings suggest that endophyte ability of increasing antioxidant contents in plants may reduce the oxidative damage caused by stresses and that the fungal regulation of plant antioxidants would partly explain the accumulation of these compounds in plant tissues.

N6-Methyladenosine (m6A) Sequencing Reveals Heterodera glycines-Induced Dynamic Methylation Promoting Soybean Defense.

Unraveling the intricacies of soybean cyst nematode (Heterodera glycines) race 4 resistance and susceptibility in soybean breeding lines-11-452 (highly resistant) and Dongsheng1 (DS1, highly susceptible)-was the focal point of this study. Employing cutting-edge N6-methyladenosine (m6A) and RNA sequencing techniques, we delved into the impact of m6A modification on gene expression and plant defense responses. Through the evaluation of nematode development in both resistant and susceptible roots, a pivotal time point (3 days postinoculation) for m6A methylation sequencing was identified. Our sequencing data exhibited robust statistics, successful soybean genome mapping, and prevalent m6A peak distributions, primarily in the 3' untranslated region and stop codon regions. Analysis of differential methylation peaks and differentially expressed genes revealed distinctive patterns between resistant and susceptible genotypes. In the highly resistant line (11-452), key resistance and defense-associated genes displayed increased expression coupled with inhibited methylation, encompassing crucial players such as R genes, receptor kinases, and transcription factors. Conversely, the highly susceptible DS1 line exhibited heightened expression correlated with decreased methylation in genes linked to susceptibility pathways, including Mildew Locus O-like proteins and regulatory elements affecting defense mechanisms. Genome-wide assessments, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and differential methylation peak/differentially expressed gene overlap emphasized the intricate interplay of m6A modifications, alternative splicing, microRNA, and gene regulation in plant defense. Protein-protein interaction networks illuminated defense-pivotal genes, delineating divergent mechanisms in resistant and susceptible responses. This study sheds light on the dynamic correlation between methylation, splicing, and gene expression, providing profound insights into plant responses to nematode infection.

Electronic symptom monitoring for home-based palliative care: A systematic review.

BACKGROUND: Coordination and communication challenges in home-based palliative care complicate transitions from hospital care. Electronic symptom monitoring enables real-time data collection, enhancing patient-provider communication. However, a systematic evaluation of its effectiveness in home-based palliative care is lacking. AIM: To analyze the feasibility, effectiveness, and limitations of electronic symptom monitoring in home-based palliative care, assess the evidence quality, identify the evidence gap, and suggest implications for future research and practice. DESIGN: This study uses systematic review, meta-analysis, and narrative synthesis (CRD42023457977) to analyze relevant studies until September 2023. DATA SOURCES: Electronic searches in MEDLINE, CENTRAL, and Embase until September 2023, complemented by hand-searching of references and citations. RESULTS: This study included twenty studies. The majority of patients positively engage in electronic symptom monitoring, which could improve their quality of life, physical and emotional well-being, and symptom scores without a significant increase in costs. However, firm conclusions about the effects of electronic symptom monitoring on outcomes like survival, hospital admissions, length of stay, emergency visits, and adverse events were limited due to significant variability in the reported data or inadequate statistical power. CONCLUSION: Introducing electronic symptom monitoring in home-based palliative care holds potential for enhancing patient-reported outcomes, potentially decreasing hospital visits and costs. However, inconsistency in current studies arising from diverse monitoring systems obstructs comparability. To advance, future high-quality research should employ standardized follow-up periods and established scales to better grasp the benefits of electronic symptom monitoring in home-based palliative care.

Identification, Pathogenicity, and Fungicide Sensitivity of Colletotrichum Species Associated with Anthracnose on Italian Ryegrass in Southwestern China.

Italian ryegrass (Lolium multiflorum L.) is widely cultivated as an important forage worldwide because of its high nutritional value and good palatability. Anthracnose caused by Colletotrichum species was a common and new emerging disease of Italian ryegrass. In this study, 88 Colletotrichum isolates were collected from diseased leaves of Italian ryegrass planting regions in Sichuan, Chongqing and Guizhou provinces of southwestern China between 2019 and 2022. By pure culture technique, 15 representative single-spore isolates were obtained for further study. Multi-locus phylogenetic analysis coupled with morphological features showed that these isolates were finally identified as six new record species: C. cereale of the C. graminicola species complex, C. fioriniae and C. nymphaeae of the C. acutatum species complex, C. boninense and C. citricola of the C. boninense species complex, and C. nageiae. Pathogenicity tests indicated that all species could induce anthracnose symptoms; of these, C. cereale was more invasive than other species, followed by C. fioriniae, C. nageiae, C. citricola and C. boninense; C. nymphaeae was weakest pathogenic to Italian ryegrass plants (P ≤ 0.05). Fungicide sensitivity assays showed that iprodione, propineb and oxime·tebuconazole had strong inhibitory effect on the mycelial growth of six Colletotrichum species; in addition, azoxystrobin and fludioxonil also significantly inhibited the mycelial growth of C. nymphaeae and C. fioriniae, respectively. These results provide the basis for the diagnosis and detection in the field, pathogen identification and management of anthracnose on Italian ryegrass.

First Report of Didymella uniseptata Causing Leaf Spot on Taraxacum mongolicum in China.

Dandelion (Taraxacum mongolicum), belonging to the Asteraceae family, is one of the main associated species in the alpine meadow, and is famous for its both feeding and medicinal values (Lin et al. 2022; Wang et al. 2022). In September 2021 (vigorous growth period), a newly emerging leaf spot disease of T. mongolicum were observed on natural grassland in Ruoergai County, Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, China (33°59'51'' N, 102°44'57'' E, alt. 3414 m). Leaf disease incidence was ranged from 10% to 15%. The symptoms appeared as brown to dark brown, circular or irregular, sunken spots; eventually, the infected sites of leaves formed a hole in the middle position of lesions. For isolation, 21 tissue pieces (5mm × 5mm) from 7 symptomatic leaf samples of 4 different plants were surface sterilized with 70% ethanol for 30 s and rinsed three times with sterilized distilled water. Then, these tissues were placed on potato dextrose agar (PDA) at 25°C and incubated in the dark for 2 to 7 days. Finally, six pure Didymella strains with consistent colony characteristics were obtained from hyphal tips as described by Xue et al. (2023). Colonies on PDA were brown to black with concentric circles, and abundant black pycnidia were visible; reverse similar in color. Conidia were ellipsoidal, ovoid, hyaline, 0 to 1-septate, 4.07 to 8.67 × 2.74 to 5.35 µm (average 3.60 × 6.55 µm; n = 50). Seven-week-old healthy plants were obtained by growing T. mongolicum seeds in pots (two plants per pot). The six pure Didymella strains were subsequently used to inoculate healthy plants as follows: for each strain, eight pots were spray inoculated with a mycelial suspension of about 4 × 104 CFU/ml, referring to our previous method (Xue et al. 2023). In addition, eight pots considered as non-inoculated controls were sprayed with sterilized distilled water. All pots were individually covered with transparent polyethylene bags for 5 days to maintain high relative humidity and placed in a greenhouse at 23 to 29°C. After incubation for 10 days, the typical symptoms consisted of brown to dark brown, sunken spots, which were similar to those previously observed in nature grassland; however, symptoms were not observed on the non-inoculated plants (controls). The same fungus was reisolated from the lesions and confirmed by the morphological and molecular methods described in this note, thus fulfilling Koch's postulates. To further identify this fungal pathogen, ITS-rDNA, and two other protein-coding genes (rpb2 and tub2) of the representative strain REG28 were amplified with primers described by Chen et al. (2022). Sequences were deposited in GenBank (PP385777 for ITS, PP781948 for rpb2, and PP781947 for tub2). A maximum likelihood (RAxML) phylogenetic tree based on the combined ITS, rpb2, and tub2 alignments showed REG28, and ex-type CGMCC 3.20069 of D. uniseptata (Chen et al. 2022) formed a subclade with 100% bootstrap support (Fig. S1). The causal agent of this disease was confirmed as D. uniseptata by the morphological, molecular, and pathogenic features described above. Recently, D. macrophylla has been reported as the first record on T. officinale in Russia (Gomzhina et al. 2020). To our knowledge, this is the first report of D. uniseptata causing leaf spots on T. mongolicum worldwide. This information will be useful for the diagnosis, detection, pathogen identification and future control of this disease on T. mongolicum in natural grassland.

Regulation of mineral elements in Hordeum brevisubulatum by Epichloë bromicola under Cd stress.

In this study, wild barley (Hordeum brevisubulatum) infected (E+) and uninfected (E-) by Epichloë bromicola were used for hydroponic experiments during the seedling stage. Various attributes, such as the effect of fungal endophyte on the growth and development of wild barley, the absorption of cadmium (Cd) and mineral elements (Ca, Mg, Fe, Mn, Cu, Zn), subcellular distribution, and chemical forms were investigated under CdCl2 stress. The results showed that the fungal endophy significantly reduced the Ca content and percentage of plant roots under Cd stress. The Fe and Mn content of roots, the mineral element content of soluble fractions, and the stems in the pectin acid or protein-chelated state increased significantly in response to fungal endophy. Epichloë endophyte helped Cd2+ to enter into plants; and reduced the positive correlation of Ca-Fe and Ca-Mn in roots. In addition, it also decreased the correlation of soluble components Cd-Cu, Cd-Ca, Cd-Mg in roots, and the negative correlation between pectin acid or protein-chelated Cd in stems and mineral elements, to increase the absorbance of host for mineral elements. In conclusion, fungal endophy regulated the concentration and distribution of mineral elements, while storing more Cd2+ to resist the damage caused by Cd stress. The study could provide a ground for revealing the Cd tolerance mechanism of endophytic fungal symbionts.

The present study is the first to study the effect of fungal endophy on essential mineral elements of plants under heavy metal stress, filling a gap in the existing research. The study could be helpful to reveal the mechanism of endophytic fungi to improve the host's tolerance to heavy metals and provide a foundation for the grass-endophyte symbionts to improve heavy metal-contaminated soils as ecological grasses.

Mandibular Gorham-Stout Disease With Implanted Fibular Resorption.

Gorham-Stout disease is an extremely rare disease characterized by progressive massive osteolysis with different clinical manifestations. The pathology is characterized by vascular proliferation, leading to destruction and resorption of the bone matrix, but the exact etiology is unknown. It can occur in any part of the body, with few reports of cases involving the maxillofacial region. Herein, the authors report a case of Gorham-Stout disease of the mandible, which started by affecting the alveolar bone and progressed to the mandibular marginal branches and even to the implanted vascularized free fibula.

Review of Hard Palate Lipoma and Retrospective Clinicopathological Analysis of Patients With Oral Lipomas.

Lipomas occurring in the hard palate are extremely rare, and treating lipomas in this area presents challenges due to the thinness of soft tissue and the risk of postoperative bony surface exposure. We present a case of hard palate lipoma that was successfully removed using the partial thickness flap dissection technique. In addition, we reviewed the clinicopathological features of 20 reported cases of hard palate lipomas worldwide and retrospectively analyzed the clinical characteristics and pathological types of 68 oral lipomas in China. The use of a partial thickness flap demonstrates potential effectiveness in excising benign masses located in the hard palate. Regarding 68 patients with oral lipomas, the most commonly affected sites were the buccal region, tongue, and floor of the mouth. Histologically, simple lipomas and fibrolipomas were the predominant types observed.

Reconstruction of Extensive Maxillary Defects Using Flow-Through Fibula Free Flap With Anterolateral Thigh Free Flap.

BACKGROUND: The maxillary defects left unreconstructed or inadequately reconstructed often result in significant functional and esthetic impairments. Adequate reconstruction of extensive maxillary defects requires a sufficient volume of hard and soft tissues. METHODS: A 48-year-old male presenting bilateral extensive maxillary defects underwent secondary reconstruction with a flow-through fibula free flap in combination with an anterolateral thigh free flap. RESULTS: The use of flow-through technique allowed minimizing the problem of limited recipient vessels and the length of free flap vascular pedicle usually encountered in secondary reconstruction. The bilateral maxillary defects were successfully reconstructed, and the postoperative outcomes were uneventful. The patient was satisfied with the treatment outcomes. He is being followed up and was referred to the implantology department for the placement of osseointegrated dental implants. CONCLUSIONS: The flow-through fibula free flap, in combination with the anterolateral thigh free flap, was found reliable and feasible for this case of secondary reconstruction of bilateral maxillary defects. This technique has provided satisfactory functional and esthetic outcomes and effectively improved the patient's self-esteem.

Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial.

PURPOSE: Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery. METHODS: We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ 2 test were used to compare both groups' variables and measure the relationship between the predictor variable and the outcome variable. P <0.05 was considered significant for all analyses. RESULTS: A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time ( P =0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group ( P =0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients ( P <0.05). CONCLUSIONS: We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.

LncRNA Anxa10-203 enhances Mc1r mRNA stability to promote neuropathic pain by recruiting DHX30 in the trigeminal ganglion.

BACKGROUND: Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. METHODS: A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. RESULTS: Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. CONCLUSIONS: LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression.

Molecular assessment of oat head blight fungus, including a new genus and species in a family of Nectriaceae.

Head blight (HB) of oat (Avena sativa) has caused significant production losses in oats growing areas of western China. A total of 314 isolates, associated with HB were collected from the major oat cultivating areas of Gansu, Qinghai, and Yunnan Provinces in western China. Based on morphological characters, the isolates were initially classified into three genera, as differentiation to species was a bit difficult. Taxonomic analysis of these isolates based on muti-gene phylogenetic analyses (ITS, TEF1, TUB2, and RPB2) revealed four known Fusarium species, F. proliferatum, F. avenaceum, F. poae, and F. sibiricum, and one Acremonium specie (A. sclerotigenum). In addition, a new genus Neonalanthamala gen. nov., similar to genus Nalanthamala was introduced herein with a new combination, Neonalanthamala graminearum sp. nov., to accommodate the HB fungus. The molecular clock analyses estimated the divergence time of the Neonalanthamala and Nalanthamala based on a dataset (ITS, TUB2, RPB2), and we recognized the mean stem ages of the two genera are 98.95 Mya, which showed that they evolved from the same ancestor. N. graminearum was the most prevalent throughout the surveyed provinces. Pathogenicity test was carried out by using two different methods: seed inoculation and head inoculation. Results showed that F. sibiricum isolates were the most aggressive on the seed and head. A. sclerotigenum isolates were not pathogenic to seeds, and were developed less symptoms to the head compared to other species. Data analyses showed that the correlation of the germination potential, germination index, and dry weight of seed inoculation and disease index of plant inoculation had a highly significant negative correlation (P < 0.001). These results showed that the development of HB might be predicted by seed tests for this species. A. sclerotigenum and N. graminearum causing HB are being firstly reported on oat in the world. Similarly, F. proliferatum, F. avenaceum, F. poae and F. sibiricum causing oat HB are firstly reported in China.

Discovery and Characterization of Epichloë Fungal Endophytes from Elymus spp. in Northwest China.

Epichloë fungal endophytes hold promise in sustainable agriculture by fortifying cool-season grasses such as Elymus spp. against various stresses. Elymus spp. are widely distributed in Northwest China with a high incidence of endophyte infections. In this study, we identified 20 Epichloë endophytic fungal strains carried by five Elymus spp. from five areas of Northwest China and systematically characterized their morphology, molecular phylogeny, mating type, and alkaloid diversity for the first time. The morphological characterization underscores strain diversity, with variable colony textures and growth rates. A phylogenetic analysis confirms all strains are E. bromicola, emphasizing their taxonomic status. Alkaloid-encoding gene profiling delineates distinct alkaloid synthesis capabilities among the strains, which are crucial for host adaptability and resistance. A mating-type analysis reveals uniformity (mtAC) across the Epichloë strains, simplifying breeding strategies. Notably, the Epichloë strains exhibit diverse alkaloid synthesis gene profiles, impacting host interactions. This research emphasizes the ecological significance of Epichloë endophytes in Elymus spp. ecosystems, offering insights into their genetic diversity and potential applications in sustainable agriculture.

Association between COVID 19 exposure and expression of malignant pathological features in oral squamous cell carcinoma: A retrospective cohort study.

OBJECTIVES: To analyze the relationship between the clinical and pathological characters of OSCC and COVID 19 exposure. MATERIALS AND METHODS: A retrospective cohort study in patients with OSCC with or without COVID 19 was performed. A total of 200 OSCC patients treated with surgery from 2019 to 2023 were included. Clinical and pathological features were analysed between two groups. Characters with statistical difference were further analysed by performing univariate analysis and logistic regression analysis. RESULTS: The expression of Ki67 (n = 57, 71.3 %, P < 0.001) and CyclinD1 (n = 64, 80 %, P < 0.001) in OSCC with the exposure history of COVID 19 is higher than that in patients never exposed to COVID 19. COVID 19 exposure history is an independent influencing factor for higher expression of Ki67 (OR = 4.04, 95 % CI: 1.87-8.72, P < 0.001) and CyclinD1 (OR = 5.45, 95 % CI: 2.56-11.60, P < 0.001). CONCLUSION: COVID 19 may suggest more invasive malignant biological behavior of cancer cells in OSCC.

Interactions between Epichloë endophyte and the plant microbiome impact nitrogen responses in host Achnatherum inebrians plants.

The clavicipitaceous fungus Epichloë gansuensis forms symbiotic associations with drunken horse grass (Achnatherum inebrians), providing biotic and abiotic stress protection to its host. However, it is unclear how E. gansuensis affects the assembly of host plant-associated bacterial communities after ammonium nitrogen (NH4+-N) treatment. We examined the shoot- and root-associated bacterial microbiota and root metabolites of A. inebrians when infected (I) or uninfected (F) with E. gansuensis endophyte. The results showed more pronounced NH4+-N-induced microbial and metabolic changes in the endophyte-infected plants compared to the endophyte-free plants. E. gansuensis significantly altered bacterial community composition and ß-diversity in shoots and roots and increased bacterial α-diversity under NH4+-N treatment. The relative abundance of 117 and 157 root metabolites significantly changed with E. gansuensis infection under water and NH4+-N treatment compared to endophyte-free plants. Root bacterial community composition was significantly related to the abundance of the top 30 metabolites [variable importance in the projection (VIP) > 2 and VIP > 3] contributing to differences between I and F plants, especially alkaloids. The correlation network between root microbiome and metabolites was complex. Microorganisms in the Proteobacteria and Firmicutes phyla were significantly associated with the R00693 metabolic reaction of cysteine and methionine metabolism. Co-metabolism network analysis revealed common metabolites between host plants and microorganisms.IMPORTANCEOur results suggest that the effect of endophyte infection is sensitive to nitrogen availability. Endophyte symbiosis altered the composition of shoot and root bacterial communities, increasing bacterial diversity. There was also a change in the class and relative abundance of metabolites. We found a complex co-occurrence network between root microorganisms and metabolites, with some metabolites shared between the host plant and its microbiome. The precise ecological function of the metabolites produced in response to endophyte infection remains unknown. However, some of these compounds may facilitate plant-microbe symbiosis by increasing the uptake of beneficial soil bacteria into plant tissues. Overall, these findings advance our understanding of the interactions between the microbiome, metabolome, and endophyte symbiosis in grasses. The results provide critical insight into the mechanisms by which the plant microbiome responds to nutrient stress in the presence of fungal endophytes.

Discovery of Epichloë as novel endophytes of Psathyrostachys lanuginosa in China and their alkaloid profiling.

The Epichloë genus represents a significant group of above-ground endophytes extensively researched for their potential applications in agriculture and ecology. Additionally, Epichloë species synthesize bioactive alkaloids, which generally cause health problems in livestock and have detrimental effects on the performance of insect herbivores. Psathyrostachys lanuginosa serves as a valuable forage grass for livestock owing to its high nutritional value and resilience in adverse environmental conditions. Nevertheless, to date, no reports have documented Epichloë as endophytes of P. lanuginosa. In this study, four strains (PF5, PF9, QG2, and QG4) were isolated and identified through morphological, molecular, and phylogenetic analyses as endophytes of P. lanuginosa. Morphological analysis indicated colony characteristics and conidia features consistent with symbiotic Epichloë, with no significant differences observed in growth rates or conidia dimensions among the four strains. Phylogenetic analysis confirmed all strains as E. bromicola. Additionally, alkaloid biosynthetic genes were detected, revealing differences in the potential synthesis of peramine and indole diterpenoid alkaloids among strains from different geographic origins. However, all four E. bromicola strains exhibited similar potential for synthesizing ergot alkaloids, but not loline alkaloids. Overall, this study identified P. lanuginosa as a novel host for E. bromicola and provided insights into the alkaloid profiles of these strains, laying a solid foundation for the scientific and rational utilization of Epichloë resources.