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The G1/S transition is crucial for regulating the initiation of cell division and is highly conserved across eukaryotes. This phase of the cell cycle involves intricate transcriptional controls that are essential for understanding cell proliferation dynamics. The G1/S transition integrates diverse intracellular and extracellular signals, including growth factors and cell sizes. Saccharomyces cerevisiae, an important model organism, plays an integral role in unveiling the regulatory mechanisms of the G1/S transition. Recent studies on the G1/S transition in both yeast and vertebrates have demonstrated a direct correlation between dysregulation of the G1/S transition and the development of cancer. This review explores the G1/S transition regulatory network and its association with cancer formation, providing a theoretical foundation for future research in fundamental cell cycle dynamics and cancer.

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 fungal pathogen Setosphaeria turcica causes northern corn leaf blight (NCLB) in maize, sorghum, and related grasses. NCLB is a serious fungal foliar disease of cultivated maize that causes devastating yield losses. S. turcica infects maize leaves by means of a specialized cell, the appressorium, but the regulatory mechanisms that underlie appressorium-mediated infection remain largely unknown. Many regulatory pathways and a large number of genes have been described in S. turcica, and many of these genes have been cloned. Characterization of such disease-related genes is important for understanding the biological mechanisms of interaction between pathogen and host and can guide the development of strategies for disease control. There is a significant level of concern regarding the possible dissemination of the S. turcica pathogen to regions where NCLB is not presently prevalent. This scenario is of considerable concern and necessitates immediate research intervention. The present review brings together information on the epidemiology and infection mechanisms of S. 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.

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 STATEMENT What 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.

Abstract 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.

Psoriasis is a common chronic recurrent disease in dermatology. IL-23 / Th17 axis plays a critical role in the pathogenesis of psoriasis. In psoriasis patients, the gut-microbiota-skin axis may exit. Gut microbiota dybiosis may be involved in the pathogenesis of psoriasis by inducing the intestinal mucosal barrier dysfunction, bacterial translocation, inducing excessive activation of Th17, and suppressing the differention of regulatory T cells. We reviewed the recent advances of potential relation between psoriasis and gut microbiota. Probiotics and fecal microbiota transplantation could be novel therapy for psoriasis.

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.

ObjectiveRoutine 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.MethodsPatients 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).ResultsA 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.ConclusionRoutine 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.

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.

ObjectiveThe 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.MethodsWe 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).ResultsA 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.ConclusionsAdjuvant 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.

As a valuable and powerful platform technology, yeast surface display (YSD) has been widely used in various biotechnological fields, but little in agricultural applications. Xylanase can be used as an elicitor in the plant–pathogen interaction system and induce corn defence response. In this study, the YSD technology was used to express the xylanase protein family from Setosphaeria turcica, which is a novel strategy for plant protection. First, five genes encoding xylanase were selected from the S. turcica genome database. The conserved domains of these genes were analyzed, which revealed that these genes were highly conserved. Here, we selected two of the five genes and expressed them by a prokaryotic expression system, but the two xylanase genes were expressed in inclusion bodies and showed no activity. To make them available in the application, we successfully constructed them in a YSD system. The products were detected for enzyme activities and the activities of two xylanases were 16.72 and 19.12 U/mL, respectively. We finally proved that the yeast-displaying xylanase was an efficient strategy to induce corn defence response, as four defence genes in corn, PR-1, PR-4, SOD and CAT were induced after treatment with the yeast displaying xylanases.

Cip1, a newly identified yeast analog of p21, is a Cln3-CDK inhibitor that negatively regulates cell-cycle START. However, its function remains poorly understood. In this study, we found that deletion of CLN3 did not result in bypass of G1-phase arrest caused by Cip1 overexpression. Cip1 depletion in cln3-null mutants significantly advanced the timing of Cln2 expression, supporting the idea that Cip1 represses START in a Cln3-independent manner. We set to search for novel Cip1 interacting proteins and found that Ccr4, a known START regulator, and its associated factor Caf120, interact with Cip1. Ccr4-Caf120 acts redundantly with Cdk1-Cln3 to inhibit Whi5-mediated regulation of START. This interaction was conserved between human Ccr4 and p21. In addition, deletion of WHI5 robustly suppressed G1-phase arrest caused by Cip1 overexpression. We conclude that Cip1 negatively regulates START by acting as a dual repressor of Ccr4 in parallel with Cln3.

Heterotrimeric G proteins are best known for their role in the transduction of extracellular signals to various downstream effectors. G proteins in higher eukaryotes are intensively studied; however, their roles in foliar pathogens are still elusive. In this study, we cloned the gene Stgg1 encoding G protein γ subunit in Setosphaeria turcica and investigated its function by RNA interference technology. Three independent Stgg1 targeted RNAi mutants R3, R5 and R6 with diverse silencing efficiency were generated. Knock-down of Stgg1 resulted in a significant reduction in mRNA levels of the genes encoding Gα (Stga1, Stga2, Stga3) but not for Gβ (Stgb1). Stgg1 RNAi mutants exhibited significantly elongated hyphal cells with blocked conidium production. In addition, Stgg1 RNAi mutants all appeared in lighter colony colour compatible with inhibited secondary metabolites. Further assays demonstrated that Stgg1 was required for biosynthesis of melanin and HT-toxin activity. Furthermore, down-regulation of Stgg1 largely inhibited the inflection capacity. Thus, we proposed that Stgg1 played crucial roles in conidiation, secondary metabolite production and pathogenicity of S. turcica and is, therefore, an ideal target for drug design against foliar pathogens.

Abstract Background Recent development of DNA assembly technologies has spurred myriad advances in synthetic biology, but new tools are always required for complicated scenarios. Here, we have developed an alternative DNA assembly method named AFEAP cloning (Assembly of Fragment Ends After PCR), which allows scarless, modular, and reliable construction of biological pathways and circuits from basic genetic parts. Methods The AFEAP method requires two-round of PCRs followed by ligation of the sticky ends of DNA fragments. The first PCR yields linear DNA fragments and is followed by a second asymmetric (one primer) PCR and subsequent annealing that inserts overlapping overhangs at both sides of each DNA fragment. The overlapping overhangs of the neighboring DNA fragments annealed and the nick was sealed by T4 DNA ligase, followed by bacterial transformation to yield the desired plasmids. Results We characterized the capability and limitations of new developed AFEAP cloning and demonstrated its application to assemble DNA with varying scenarios. Under the optimized conditions, AFEAP cloning allows assembly of an 8 kb plasmid from 1-13 fragments with high accuracy (between 80 and 100%), and 8.0, 11.6, 19.6, 28, and 35.6 kb plasmids from five fragments at 91.67, 91.67, 88.33, 86.33, and 81.67% fidelity, respectively. AFEAP cloning also is capable to construct bacterial artificial chromosome (BAC, 200 kb) with a fidelity of 46.7%. Conclusions AFEAP cloning provides a powerful, efficient, seamless, and sequence-independent DNA assembly tool for multiple fragments up to 13 and large DNA up to 200 kb that expands synthetic biologist’s toolbox.

Abstract Technologies development for seamless gene editing and marker recycling has allowed frequent genomic engineering in Saccharomyces cerevisiae for desired laboratory strains and cell factory. Alternative new approaches are still required for complicated scenarios. In this study, we report that inducible overexpression of cell wall protein 1 (Cwp1) by galactose addition confers yeast cells a robust growth inhibition. Direct repeats flanking the Gal‐CWP1:selectable marker cassette allow for its homology recombination excision and counter selection upon galactose addition, therefore enable seamless gene editing and marker recycling. We used this strategy and efficiently generated scarless Ade8 deletion mutants. Our results highlight the utility of lethal effect of Cwp1 overexpression a new counter selection strategy and a simple and efficient method for seamless gene editing and marker recycling in S. cerevisiae and potentially other fungi.

This article discusses a case of Mycobacterium marinum infection on the thigh and hip that was initially misdiagnosed as tinea cruris. The patient, a 37-year-old man with a history of fishing, had persistent lesions for over 2 years despite treatment with antifungal drugs. The diagnosis was confirmed through histopathological analysis, positive acid-fast stain, and bacterial culture. The patient was successfully treated with a combination of antibiotics. The article emphasizes the importance of considering uncommon pathogens in cases of chronic cutaneous lesions, particularly in patients with relevant exposures or hobbies. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]