The genome sequencing and comparative genomics analysis of Rhizoctonia solani reveals a novel effector family owning a uinque domain in Basidiomycetes.

Rhizoctonia solani is a soil-borne pathogen with 14 anastomosis groups (AGs), and different subgroups are genetically diverse. However, the genetic factors contributing to the pathogenicity of the fungus have not been well characterized. In this study, the genome of R. solani AG1-ZJ was sequenced. As the result, a 41.57 Mb draft genome containing 12,197 putative coding genes was obtained. Comparative genomic analysis of 11 different AGs revealed conservation and unique characteristics between the AGs. Furthermore, a novel effector family containing a 68 amino acid conserved domain unique in basidiomycetous fungi was characterized. Two effectors containing the conserved domain in AG4-JY were identified, and named as RsUEB1 and RsUEB2. Furthermore, the spray-induced gene silencing strategy was used to generate a dsRNA capable of silencing the conserved domain sequence of RsUEB1 and RsUEB2. This dsRNA can significantly reduce the expression of RsUEB1 and RsUEB2 and the pathogenicity of AG4-JY on foxtail millet, maize, rice and wheat. In conclusion, this study provides significant insights into the pathogenicity mechanisms of R. solani. The identification of the conserved domain and the successful use of dsRNA silencing of the gene containing the conserved domain will offer a new strategy for controlling sheath blight in cereal crops.

Unveiling the In Situ Evolution of Li2O-Rich Solid Electrolyte Interface on CoOx Embedded Carbon Fibers as Li Anode Host.

Modification of three-dimensional (3D) carbon hosts with metal oxides has been considered as advantageous for the formation of Li2O-rich solid electrolyte interface (SEI), which can show fast Li+ diffusion, and meanwhile alleviate dendrite problems caused by fragility and nonuniformity of native SEIs. However, the lack of convincing experimental evidence has made it difficult to unveil the true origin of oxygen in Li2O-rich SEIs until now. Herein, CoOx embedded carbon nanofibers (CNF-CoOx) are successfully prepared as high-performance Li anode hosts. By employing 18O isotope labeling, the role of CoOx during SEI evolution is elucidated, revealing that CoOx contributes significantly to Li2O formation by delivering oxygen. Benefiting from the rich Li2O content, the as-formed SEIs greatly improve the Li+ migration kinetics, and therefore, the CNF-CoOx@Li anode can exhibit excellent cycling stability in half, symmetrical, and full cells.

Molecular characterization revealed the role of thaumatin-like proteins of Rhizoctonia solani AG4-JY in inducing maize disease resistance.

The gene family of thaumatin-like proteins (TLPs) plays a crucial role in the adaptation of organisms to environmental stresses. In recent years, fungal secreted proteins (SP) with inducing disease resistance activity in plants have emerged as important elicitors in the control of fungal diseases. Identifying SPs with inducing disease resistance activity and studying their mechanisms are crucial for controlling sheath blight. In the present study, 10 proteins containing the thaumatin-like domain were identified in strain AG4-JY of Rhizoctonia solani and eight of the 10 proteins had signal peptides. Analysis of the TLP genes of the 10 different anastomosis groups (AGs) showed that the evolutionary relationship of the TLP gene was consistent with that between different AGs of R. solani. Furthermore, it was found that RsTLP3, RsTLP9 and RsTLP10 were regarded as secreted proteins for their signaling peptides exhibited secretory activity. Prokaryotic expression and enzyme activity analysis revealed that the three secreted proteins possess glycoside hydrolase activity, suggesting they belong to the TLP family. Additionally, spraying the crude enzyme solution of the three TLP proteins could enhance maize resistance to sheath blight. Further analysis showed that genes associated with the salicylic acid and ethylene pathways were up-regulated following RsTLP3 application. The results indicated that RsTLP3 had a good application prospect in biological control.

The catalytic subunit of type 2A protein phosphatase negatively regulates conidiation and melanin biosynthesis in Setosphaeria turcica.

Northern corn leaf blight caused by Setosphaeria turcica is a major fungal disease responsible for significant reductions in maize yield worldwide. Eukaryotic type 2A protein phosphatase (PP2A) influences growth and virulence in a number of pathogenic fungi, but little is known about its roles in S. turcica. Here, we functionally characterized S. turcica StPP2A-C, which encodes the catalytic C subunit of StPP2A. StPP2A-C deletion slowed colony growth, conidial germination, and appressorium formation but increased conidiation, melanin biosynthesis, glycerol content, and disease lesion size on maize. These effects were associated with expression changes in genes related to calcium signaling, conidiation, laccase activity, and melanin and glycerol biosynthesis, as well as changes in intra- and extracellular laccase activity. A pull-down screen for candidate StPP2A-c interactors revealed an interaction between StPP2A-c and StLac1. Theoretical modeling and yeast two-hybrid experiments confirmed that StPP2A-c interacted specifically with the copper ion binding domain of StLac1 and that Cys267 of StPP2A-c was required for this interaction. StPP2A-C expression thus appears to promote hyphal growth and reduce pathogenicity in S. turcica, at least in part by altering melanin synthesis and laccase activity; these insights may ultimately support the development of novel strategies for biological management of S. turcica.

The Septin Gene StSep4 Contributes to the Pathogenicity of Setosphaeria turcica by Regulating the Morphology, Cell Wall Integrity, and Pathogenic Factor Biosynthesis.

Septins are a conserved group of GTP-binding proteins found in all eukaryotes and are the fourth-most abundant cytoskeletal proteins. Septins of some pathogenic fungi are involved in morphological changes related to infection. Our previous studies have identified four core septins (StSep1-4) in Setosphaeria turcica, the causal agent of northern corn leaf blight, while only StSep4 is significantly upregulated during the invasive process. We therefore used forchlorfenuron (FCF), the specific inhibitor of septin, and ΔStSep4 knockout mutants to further clarify the role of septins in S. turcica pathogenicity. FCF treatment caused a dose-dependent reduction in S. turcica colony growth, delayed the formation of infection structures, and reduced the penetration ability. ΔStSep4 knockout mutants displayed abnormal mycelium morphology, slow mycelial growth, conidiation deficiency, delayed appressorium development, and weakened pathogenicity. StSep4 deletion also broke cell wall integrity, altered chitin distribution, decreased the melanin content, and disrupted normal nuclear localization. A transcriptomic comparison revealed that genes differentially expressed between ΔStSep4 and WT were enriched in terms of ribosomes, protein translation, membrane components, and transmembrane transport activities. Our results demonstrate that StSep4 is required for morphology and pathogenicity in S. turcica, making it a promising target for the development of novel fungicides.

Survival benefit of surgical treatment for patients with stage IVB endometrial cancer: a propensity score-matched SEER database analysis.

The study aimed to evaluate the value of cancer-directed surgery (CDS) in improving the prognosis of patients with stage IVB endometrial cancer (EC) and under which kind of conditions could maximise its value. The Surveillance, Epidemiology, and End Results database was used to analyse patients diagnosed with stage IVB EC who received chemotherapy between 2004 and 2016. Among 1978 patients were enrolled following propensity score matching (PSM). We found that CDS was closely associated with prolonged overall survival. Moreover, CDS can effectively improve the survival rate of patients with protective or unfavourable factors and should be considered in a range of circumstances. Almost all patients (96.15%) who received surgery were operated on primary tumours of the reproductive organs and obtained favourable surgical outcomes. In conclusion, surgery can improve the survival of patients with stage IVB EC, palliative hysterectomy is worth considering in such patients.IMPACT STATEMENTWhat is already known on this subject? Patients with stage IVB EC account for a small proportion, so previous researches usually had an insufficient sample size. And it is still controversial whether to perform surgery on patients with stage IVB EC.What do the results of this study add? We verified the value of CDS in improving prognosis of patients with stage IVB EC. We also found that surgery outcomes were better in patients aged ˂ 60 years, and with T1 and T2 invasion. Moreover, resection of the primary site played an important role in prolonging survival time.What are the implications of these findings for clinical practice and/or further research? Surgical treatment can prolong the overall survival of patients with stage IVB EC, even if only primary site resection is performed. Surgery should be more aggressive in patients aged ˂ 60 years, and with lesions confined in the pelvis (with T1 and T2 invasion). The survival rate of patients with brain metastasis may also be improved by surgery. However, because of the small sample size, the surgical benefit needs further confirmation.

The survival impact of adjuvant radiotherapy and chemotherapy in patients with non-endometrioid endometrial carcinomas: a PSM-IPTW analysis based on SEER database.

PURPOSE: To investigate outcomes of adjuvant treatments for non-endometrioid endometrial carcinomas (NEEC), as previous studies are limited by its rarity and heterogeneity. PATIENTS AND METHODS: Patients with endometrial serous carcinoma (SC), clear cell carcinoma (CCC) and carcinosarcoma were identified between 2004 and 2018 from SEER database. Propensity score matching (PSM) along with inverse probability treatment weighting (IPTW) technique were employed to balance confounding factors. Multivariate, exploratory subgroup and sensitivity analyses were conducted to evaluate the impact of adjuvant treatment on overall survival (OS) and cause-specific survival (CSS). RESULTS: The cohort comprised 5577 serous, 977 clear cell, and 959 carcinosarcomas. Combined chemotherapy and radiotherapy (CRT), chemotherapy alone, and radiotherapy alone were respectively administered in 42.21%, 47.27% and 10.58% of the whole cohort. Prior to adjusting, chemotherapy plus brachytherapy yielded the most beneficial effect among various strategies. After PSM-IPTW adjustment, CRT still demonstrated beneficial effect on OS and CSS. Subgroup analysis indicated CRT improved survival among various TNM stages, particularly with uterine carcinosarcoma. In the sensitivity analyses for serous histology, brachytherapy with or without chemotherapy appeared to benefit stage I-II patients. In stage III-IV SC patients, chemotherapy plus brachytherapy was still associated with improved survival outcomes. When nodal metastases were identified, additional external beam radiotherapy (EBRT) to CT was more utilized with survival improvement. CONCLUSION: In NEEC patients, combined CRT yielded beneficial effects than any single mode. Both chemotherapy and brachytherapy promoted survival in early stage SC patients. Late stage SC patients may benefit from chemotherapy plus either EBRT or brachytherapy.

Genome Resource of Rhizoctonia solani Anastomosis Group 4 Strain AG4-JY, a Pathomycete of Sheath Blight of Foxtail Millet.

The basidiomycetous fungus Rhizoctonia solani Kühn (teleomorph Thanatephorus cucumeris [Frank] Donk) is a fungal pathogen that causes various diseases on economically important crops, such as foxtail millet, maize, and rice. Using the PacBio Sequel platform, we assembled a draft genome of an R. solani strain AG4-JY that was isolated from foxtail millet with sheath blight at the stem. The genome was approximately 43.43 Mb on 53 scaffolds, with a scaffold N50 length of 2.10 Mb. In all, 10,545 genes and 179 noncoding RNAs were predicted, and 10,488 genes had at least one database annotation. In addition, the proteins encoded by 709 genes were predicted as secretory proteins. The AG4-JY genome sequence provides a valuable resource for understanding the interactions between R. solani and foxtail millet and controls sheath blight in the world.

StRAB4 gene is required for filamentous growth, conidial development, and pathogenicity in Setosphaeria turcica.

Setosphaeria turcica, the fungal pathogen responsible for northern corn leaf blight in maize, forms specialized infectious structures called appressoria that are critical for fungal penetration of maize epidermal cells. The Rab family of proteins play a crucial role in the growth, development, and pathogenesis of many eukaryotic species. Rab4, in particular, is a key regulator of endocytosis and vesicle trafficking, essential for filamentous growth and successful infection by other fungal pathogens. In this study, we silenced StRAB4 in S. turcica to gain a better understanding the function of Rab4 in this plant pathogen. Phenotypically, the mutants exhibited a reduced growth rate, a significant decline in conidia production, and an abnormal conidial morphology. These phenotypes indicate that StRab4 plays an instrumental role in regulating mycelial growth and conidial development in S. turcica. Further investigations revealed that StRab4 is a positive regulator of cell wall integrity and melanin secretion. Functional enrichment analysis of differentially expressed genes highlighted primary enrichments in peroxisome pathways, oxidoreductase and catalytic activities, membrane components, and cell wall organization processes. Collectively, our findings emphasize the significant role of StRab4 in S. turcica infection and pathogenicity in maize and provide valuable insights into fungal behavior and disease mechanisms.

Anaerobic solid-state fermentation with Bacillus subtilis for digesting free gossypol and improving nutritional quality in cottonseed meal.

Microbial fermentation is an effective method to degrade free-gossypol, which is a toxic substance restricting the utilization of cottonseed meal in animal husbandry. However, there are few researches on the nutritional effect and the change of bacterial community on cottonseed meal fermented with anaerobic solid-state fermentation. This study evaluated the effects of fermentation with Bacillus sp. on gossypol degradation and nutritional quality improvement in cottonseed meal (CM), as well as the changes of bacterial community structure during fermentation. The strains with high activity for digesting free gossypol were screened from high protease-producing strains preserved in the laboratory. Then the strains which had both the gossypol degradation activity and protease producing activity were selected to degrade macromolecular protein and free gossypol in CM. The unsterilized SSF medium was inoculated with 109 CFU/kg Bacillus culture and fermented at room temperature for 14 days. Each group had three parallels. And the effects of anaerobic solid-state fermentation on unsterilized CM was evaluated. Results showed that for the seven strains with high activity for digesting free gossypol and producing protease that were screened, free gossypol content in fermented cottonseed meal (FCM) decreased and acid-soluble protein (ASP) contents increased. Among them, strain M-15 had the best fermentation effect, with the free gossypol degradation rate of 93.46% and acid soluble protein content of 13.26%. M-15 was identified as Bacillus subtilis. During fermentation with M-15, the bacterial diversity in CM was reduced, but not significant and the community structure was simpler significantly. The strain M-15 selected in this experiment reduced the free gossypol content and improved the nutritional quality of CM through anaerobic solid-state fermentation, which can be used for industrial large-scale production.

Vacuum-Induced Guest N,N'-Diethylformamide Binding in a Metastable Cd5-Based Metal-Organic Framework.

A three-dimensional (3D) metal-organic framework (MOF) of [Et2NH2]2[Cd5(BTB)4(DEF)2]·4.75DEF (1; H3BTB = benzene-1,3,5-tribenzoic acid and DEF = N,N'-diethylformamide) sustained by symmetrical Z-shaped Cd5 secondary building units (SBUs) with an intrinsically metastable host framework has been prepared and characterized. Upon gentle vacuum (800 Pa) at 50 °C, some encapsulated DEF solvates are released, leading to pore-shape changes and Cd2+ coordination geometry distortion. This is followed by DEF solvate migration to only one end of the SBU with concomitant symmetry breaking. Additional time under vacuum promoted further structural distortion and topology changes as authenticated by single-crystal X-ray diffraction studies. This work was initially inspired by unusual gas adsorption isotherms and points to the potentially complicated, nonspectator role of coordinative solvents such as DEF during MOF activation.

Protein kinase A participates in hyphal and appressorial development by targeting Efg1-mediated transcription of a Rab GTPase in Setosphaeria turcica.

The cyclic adenosine monophosphate (cAMP) signalling pathway plays an important role in the regulation of the development and pathogenicity of filamentous fungi. cAMP-dependent protein kinase A (PKA) is the conserved element downstream of cAMP, and its diverse mechanisms in multiple filamentous fungi are not well known yet. In the present study, gene knockout mutants of two catalytic subunits of PKA (PKA-C) in Setosphaeria turcica were created to illustrate the regulatory mechanisms of PKA-Cs on the development and pathogenicity of S. turcica. As a result, StPkaC2 was proved to be the main contributor of PKA activity in S. turcica. In addition, it was found that both StPkaC1 and StPkaC2 were necessary for conidiation and invasive growth, while only StPkaC2 played a negative role in the regulation of filamentous growth. We reveal that only StPkaC2 could interact with the transcription factor StEfg1, and it inhibited the transcription of StRAB1, a Rab GTPase homologue coding gene in S. turcica, whereas StPkaC1 could specifically interact with a transcriptional regulator StFlo8, which could rescue the transcriptional inhibition of StEfg1 on StRAB1. We also demonstrated that StRAB1 could positively influence the biosynthesis of chitin in hyphae, thus changing the filamentous growth. Our findings clarify that StPkaC2 participates in chitin biosynthesis to modulate mycelium development by targeting the Efg1-mediated transcription of StRAB1, while StFlo8, interacting with StPkaC1, acts as a negative regulator during this process.

The role of postoperative radiotherapy in patients with uterine sarcomas: A PSM-IPTW analysis based on SEER database.

Objective: The optimal adjuvant therapy for uterine sarcomas remains poorly determined due to its rarity and histological diversity. The purpose of the study is to explore and characterize the association between utilization of radiotherapy and survival outcome in patients with surgically resected uterine sarcomas. Methods: We collected data regarding uterine sarcomas which were confirmed after total hysterectomy between 2010 and 2018 period from the latest version of the Surveillance, Epidemiology, and End Results (SEER) database. Initially, 1-, 3- and 5-year survival rate were calculated to predict potential risk factors and possible role of adjuvant chemotherapy and radiotherapy. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) technique were employed to balance confounding factors in the utilization of additional therapy. Multivariate and exploratory subgroup analyses were respectively conducted to evaluate the impact of adjuvant therapy on overall survival (OS) and cause-specific survival (CSS). Results: A total of 2897 patients were enrolled in the analysis. Survival benefit at 1-, 3-and 5-year after initial treatment was observed in the group of radiotherapy given, however, poorer prognosis in the group of chemotherapy administration. Accordingly, chemotherapy was enrolled as a confounding factor when stratifying and matching patients by receipt of radiotherapy. Prior to and after PSM-IPTW adjustment, radiotherapy both demonstrated beneficial effect on OS and CSS based on multivariate analysis. Further subgroup analysis indicated radiotherapy improved OS and CSS among a subset of patients in stage II-IV, particularly with uterine leiomyosarcoma, tumor grade IV, bigger tumor size than 100 mm and even with chemotherapy administration. Conclusions: Adjuvant radiotherapy in uterine sarcomas after hysterectomy might be underutilized, and proper use of adjuvant radiotherapy combined with chemotherapy after surgery in advanced-stage and high-risk patients might improve survival.

Novel factors contributing to fungal pathogenicity at early stages of Setosphaeria turcica infection.

The fungal pathogen Setosphaeria turcica causes leaf blight on maize, which leads to considerable crop losses. However, how S. turcica establishes sustained systemic infection is largely unknown. Here, we report several novel factors contributing to S. turcica pathogenicity, identified using a genomic and transcriptional screen at different stages of S. turcica appressorium development. We identified two cytoskeleton regulators, SLM1 and SLM2, that are crucial for hypha and appressorium development. The SLM1 and SLM2 transcripts accumulated during germling stage but their levels were notably reduced at the appressorium stage. Deletion of SLM2 dramatically affected cell morphology, penetration ability, and pathogenicity. We also identified three different types of S. turcica glycosyl hydrolases that are critical for plant cell wall degradation. Their transcripts accumulated during the appressorium infection stage induced by cellophane and maize leaf. Most importantly, we characterized a novel and specific S. turcica effector, appressorium-coupled effector 1 (StACE1), whose expression is coupled to appressorium formation in S. turcica. This protein is required for maize infection and induces cell death on expression in Nicotiana benthamiana. These observations suggest that the phytopathogen S. turcica is primed in advance with multiple strategies for maize infection, which are coupled to appressorium formation at the early infection stages.

Ferroptosis: Mechanism and connections with cutaneous diseases.

Ferroptosis is a recognized novel form of programmed cell death pathway, featuring abnormalities in iron metabolism, SystemXc-/glutathione axis, and lipid peroxidation regulation. A variety of ferroptosis inducers can influence glutathione peroxidase directly or indirectly via diverse pathways, leading to decreased antioxidant capacity, accumulated cellular lipid peroxides, and finally inducing ferroptosis. To date, mounting studies confirm the association of ferroptosis with various cutaneous diseases, including skin homeostasis, neoplastic diseases, infectious diseases, genetic skin disease, inflammatory skin diseases, and autoimmune diseases. There are shared characteristics regarding ferroptosis and various cutaneous diseases in terms of pathophysiological mechanisms, such as oxidative stress associated with iron metabolism disorder and accumulated lipid peroxides. Therefore, we summarize the current knowledge regarding the mechanisms involved in the regulation of ferroptosis for further discussion of its role in the pathogenesis and prognosis of skin diseases. Gaining insight into the underlying mechanisms of ferroptosis and the associated dermatological disorders could illuminate the pathogenesis and treatments of different cutaneous diseases.

The impact of omentectomy on cause-specific survival of Stage I-IIIA epithelial ovarian cancer: A PSM-IPTW analysis based on the SEER database.

Objective: Routine omentectomy is generally performed during surgery for patients with epithelial ovarian cancer (EOC). The current study aims to evaluate the impact of omentectomy on cause-specific survival of Stage I-IIIA EOC patients. Methods: Patients who presented with clinical Stage I-IIIA serous, clear cell, endometrioid, and mucinous ovarian cancers were selected from the SEER Database for the period between 2004 and 2018. We extracted clinicopathological data and surgical information with the focus on the performance of omentectomy and lymphadenectomy. Binary logistic regression and recursive partitioning analyses were conducted to identify the significant factors for the performance of omentectomy during surgery. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were utilized to balance confounding factors. Multivariate, exploratory subgroup analyses and sensitivity analyses were conducted to evaluate the impact of omentectomy on cause-specific survival (CSS). Results: A total of 13,302 patients with EOC were enrolled in the study. The cohort comprised 3,569 endometrioid, 4,915 serous, 2,407 clear cell, and 2,411 mucinous subtypes. A total of 48.62% (6,467/13,302) of patients underwent the procedure of omentectomy during primary surgery, and only 3% absolute improvement in CSS at the individual level was observed, without statistical significance based on multivariate analysis. According to the regression-tree model with recursive partitioning analysis, the procedure of lymphadenectomy was found to be the strongest factor to distinguish the performance of omentectomy, followed by the tumor stage. Patients who underwent omentectomy were more likely to be managed in Stage I than those who underwent lymphadenectomy. After PSM-IPTW adjustment, the inclusion of omentectomy in the initial surgical procedure did not demonstrate a beneficial impact on CSS compared with those who did not undergo the procedure. Exploratory subgroup analysis indicated that the performance of omentectomy improved 5-year CSS in Stage II-IIIA patients. In the sensitive analyses for various tumor stages, omentectomy appeared to benefit only Stage II patients. However, patients across various stages seemed to benefit from the performance of lymphadenectomy, irrespective of the performance of omentectomy on them. Conclusion: Routine omentectomy may not be associated with survival benefit for patients with a grossly normal-appearing omentum, especially for those with clinical Stage I epithelial ovarian cancers.

Association between interleukin-17F rs763780 polymorphism and psoriasis risk: A meta-analysis.

BACKGROUND: The polymorphism of interleukin-17F rs763780 has been found to have a probable association with increased risk of developing psoriasis. AIMS: This study aims to get a more convincing estimation of the association between the interleukin-17F rs763780 T /C polymorphism and psoriasis risk. METHODS: Two authors independently searched the databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Databases for case-control studies which reported the odds ratios with 95% confidence intervals comparing genotype and allele frequencies of the interleukin-17F rs763780 polymorphism in patients with psoriasis versus participants without psoriasis. RESULTS: A total of seven case-control studies incorporating 1824 cases and 1585 controls were identified. The pooled odds ratios indicated that interleukin-17F rs763780 C allele was a risk factor for psoriasis in allele frequency, recessive model and homozygote model (P < 0.05). Subgroup analysis by ethnicity further indicated that the C allele was closely related to increased risk of psoriasis in Asian populations (P < 0.05), but not in Caucasians. LIMITATIONS: Only a few studies on the interleukin-17F rs763780 polymorphism in psoriasis have been reported till date, thus the data is insufficient. Only one gene polymorphic site was selected for this study, and it is not clear whether other genetic mutation functional sites affect the gene. Further studies on confounding effects of other genetic polymorphisms are needed. CONCLUSION: The present meta-analysis results suggested that the interleukin-17F rs763780 T /C is significantly associated with psoriasis risk in Asians.