Efficacy and Safety of 125I Seed Implantation in the Treatment of Pelvic Recurrent Cervical Cancer Following Radiotherapy: A Single-Arm Meta-Analysis of Chinese Patients.

BACKGROUND: The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. RECENT FIDINGS: The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. CONCLUSION: In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. TRIAL REGISTRATION: PROSPERO: CRD42023423857.

A single amino acid substitution in the AAA-type ATPase LRD6-6 activates immune responses but decreases grain quality in rice.

Plant spotted leaf (spl) mutants are useful to reveal the regulatory mechanisms of immune responses. Thus, in crop plants, their agronomic traits, especially the grain quality are usually ignored. Here, we characterized a rice spl mutant named spl-A (spotted leaf mutant from A814) that shows autoimmunity, broad-spectrum disease resistance and growth deterioration including decreased rice quality. A single nucleotide mutation of C1144T, which leads to change of the 382nd proline to serine, in the gene encoding the ATPases associated with diverse cellular activities (AAA)-type ATPase LRD6-6 is responsible for the phenotype of the spl-A mutant. Mechanistically, this mutation impairs LRD6-6 ATPase activity and disrupts its interaction with endosomal sorting complex required for transport (ESCRT)-III subunits OsSNF7.1/7.2/7.3. And thus, leading to compromise of multivesicular bodies (MVBs)-mediated vesicle trafficking and accumulation of ubiquitinated proteins in both leaves and seeds of spl-A. Therefore, the immune response of spl-A is activated, and the growth and grain quality are deteriorated. Our study identifies a new amino acid residue that important for LRD6-6 and provides new insight into our understanding of how MVBs-mediated vesicle trafficking regulates plant immunity and growth, including grain quality in rice.

Beneficial effects of Bacillus mojavensis strain MTC-8 on plant growth, immunity and disease resistance against Magnaporthe oryzae.

Rice blast, a prevalent and highly destructive rice disease that significantly impacts rice yield, is caused by the rice blast fungus. In the present study, a strain named MTC-8, identified as Bacillus mojavensis, was demonstrated has strong antagonistic activity against the rice blast fungus, Rhizoctonia solani, Ustilaginoidea virens, and Bipolaria maydis. The potential biocontrol agents were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis and chromatography. Further investigations elucidated the inhibitory mechanism of the isolated compound and demonstrated its ability to suppress spore germination, alter hyphal morphology, disrupt cell membrane integrity, and induce defense-related gene expression in rice. MTC-8 promoted plant growth and may lead to the development of a biocontrol agent that meets agricultural standards. Overall, the Bacillus mojavensis MTC-8 strain exerted beneficial effects on plant growth, immunity and disease resistance against rice blast fungus. In this study, we isolated and purified a bioactive substance from fermentation broth, and the results provide a foundation for the development and application of biopesticides. Elucidation of the inhibitory mechanism against rice blast fungus provides theoretical support for the identification of molecular targets. The successful development of a biocontrol agent lays the groundwork for its practical application in agriculture.

MTP family analysis and association study reveal the role of ZmMTP11 in lead (Pb) accumulation.

The metal tolerance protein (MTP) gene family plays an essential role in the transport of heavy metals, however the function of the MTP family in transporting lead (Pb) was still unclear in plants. In this study, we identified and characterized 12 ZmMTPs in the whole genome of maize. These ZmMTP genes were divided into three subfamilies in evolution, namely Zn-CDF, Zn/Fe-CDF, Mn-CDF subfamilies, which showed diverse expression patterns in different tissues of maize. Using gene-based association analyses, we identified a Pb accumulation-related MTP member in maize, ZmMTP11, which was located in plasma membrane and had the potential of transporting Pb ion. Under the Pb treatment, ZmMTP11 showed a generally decreased expression relative to the normal conditions. Heterologous expressions of ZmMTP11 in yeast, Arabidopsis, and rice demonstrated that ZmMTP11 enhanced Pb accumulation in the cells without affecting yeast and plant growth under Pb stress. Remarkably, the increased Pb concentration in the plant roots did not cause changes in Pb content in the shoots. Our study provides new insights into the genetic improvement of heavy metal tolerance in plants and contributes to bioremediation of Pb-contaminant soils.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

GDF3 Protects Mice against Sepsis-Induced Acute Lung Injury by Suppression of Macrophage Pyroptosis.

Sepsis-induced ALI is marked by physiological, pathological, and biochemical irregularities caused by infection. Growth differentiation factor 3 (GDF3) is closely associated with the inflammatory response. Accumulating evidence has demonstrated a close relationship between GDF3 expression and the severity and prognosis of sepsis. However, the precise mechanism by which GDF3 protects against ALI induced by sepsis is still unclear. Following the intravenous administration of GDF3 in this research, we noted a rise in the survival rate, a decrease in the severity of histopathological damage as evaluated through HE staining, a decline in the count of inflammatory cells in bronchoalveolar lavage fluid (BALF), a reduction in the ratio of lung wet/dry (W/D) weight, and a noteworthy decrease in the levels of pro-inflammatory cytokines in both serum and BALF when compared to septic mice who underwent cecal ligation and puncture (CLP). These collective findings unequivocally indicate the protective effects of GDF3 against sepsis-induced ALI. In addition, the GDF3 group showed a significant reduction in the mRNA expression of Caspase-1 and NLRP3 when compared to the CLP group. Following this, we performed in vitro tests to confirm these discoveries and obtained comparable outcomes, wherein the administration of GDF3 notably decreased the levels of Caspase-1 and NLRP3 mRNA and protein in macrophages in comparison to the LPS group. Furthermore, GDF3 exhibited the capacity to reduce the secretion of inflammatory molecules from macrophages. By illuminating the mechanism by which GDF 3 regulates macrophages, this offers a theoretical basis for preventing and treating sepsis-induced ALI.

Plasma free fatty acid levels in cervical cancer: concurrent chemoradiotherapy improves abnormal profile.

Background: Epidemiology has demonstrated that plasma free fatty acids (FFAs) can prevent the development of cancer. Our study sought to evaluate the relationship between plasma (FFA) levels and cervical cancer. Methods: In recent years, metabolomics-based approaches have been recognized as an emerging tool, so we examined the plasma FFA profiles of 114 patients with cervical cancer and 151 healthy people using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results: The data results were analyzed by multifactorial binary logistic regression analysis, and it was found that palmitic acid, docosahexaenoic acid (DHA), and total ω-3 fatty acids were negatively correlated with the risk of cervical cancer; whereas tetracosanoic acid was positively correlated with the risk of cervical cancer (OR, 1.026; 95% CI, 1.013-1.040; p < 0.001). Dynamic follow-up of 40 cervical cancer patients who successfully completed CCRT revealed that most fatty acid levels tended to increase after the end of treatment, except for palmitic and stearic acid levels, which were lower than before treatment. Conclusion: Plasma FFA profiles were altered in cervical cancer patients, which may be related to abnormal fatty acid metabolism in cervical cancer. The described changes in fatty acid profiles during CCRT may be related to the good functioning of CCRT. Further studies on plasma FFA composition and its changes due to CCRT in patients with cervical cancer are warranted.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Physiological and transcriptomic response reveals new insight into manganese tolerance of Celosia argentea Linn.

Celosia argentea is a manganese (Mn) hyperaccumulator with high ornamental value and strong stress resistance. It is important to understand the molecular mechanism of tolerance to heavy metals of hyperaccumulators to improve the efficiency of phytoremediation. In this study, the effects of different Mn concentrations (0, 0.8, 3, and 10 mM) on physiological characteristics and molecular changes were determined. Low concentrations of Mn increased the growth of C. argentea, while high concentrations of Mn suppressed its growth, A concentration up to 3 mM did not affect the growth of C. argentea, and the highest transfer factor (TF) was 6.16. Oxidative damage of different Mn level treatments in C. argentea was verified through relative water content, electrolyte leakage, MDA content, H2O2 content and superoxide contents. With an increase in Mn concentration, the contents of chlorophyll a, chlorophyll b, and carotenoids decreased. Our results indicated that low-concentration manganese treatment can reduce the reactive oxygen burst and MDA, soluble sugar and proline, making C. argentea have strong abiotic stress tolerance. The molecular mechanism of C. argentea after 10 mM Mn treatment was analysed through transcriptome analysis, and differentially expressed genes (DEGs) in these pathways were further verified by qRTPCR. Plantpathogen interactions, plant hormone signal transduction, the MAPK signalling pathway and the phenylpropanoid biosynthesis pathway were important in the response to Mn stress, and the heavy metal-associated isoprenylated plant protein, metal transporter Nramp, and zinc transporter play key roles in the strong ability of C. argentea to tolerate heavy metals. These results suggest that C. argentea exhibits strong manganese tolerance and provide new insight into the molecular mechanisms of plant responses to heavy metal stress.

Research progress of metabolomics in cervical cancer.

INTRODUCTION: Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. OBJECTIVES: The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. METHODS: PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. RESULTS: With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. CONCLUSION: With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Competing risk models versus traditional Cox models for prognostic factors' prediction and care recommendation in patients with advanced laryngeal squamous carcinoma: a population-based study.

PURPOSE: To explore the prognostic factors and the optimal treatment modalities for patients with stage IVA laryngeal squamous cell carcinoma (LSCC), so as to improve the survival rate of patients. METHODS: Patients with stage IVA LSCC between 2004 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We used competing risk models to build nomograms for predicting cancer-specific survival (CSS). The effectiveness of the model was assessed using the calibration curves and the concordance index (C-index). The above results were compared with the nomogram established by Cox regression analysis. The patients were grouped into low-risk and high-risk groups by competing risk nomogram formula. And the Kaplan-Meier (K-M) method and log-rank test were used to make sure that these groups had a survival difference. RESULTS: Overall, 3612 patients were included. Older age, black race, a higher N stage, a higher pathological grade, and a larger tumor size were independent risk factors for CSS; married marital status, total/radical laryngectomy, and radiotherapy were protective factors. The C-index was 0.663, 0.633, and 0.628 in the train set and 0.674, 0.639, and 0.629 in the test set of the competing risk model, and 0.672, 0.640, and 0.634 in the traditional Cox nomogram for 1, 3, and 5 years. In overall survival and CSS, the prognosis of the high-risk group was poorer than that of the low-risk group. CONCLUSION: For patients with stage IVA LSCC, a competing risk nomogram was created to help screen risk population and guide clinical decision-making.

THE IL-33/ST2 AXIS PROMOTES ACUTE RESPIRATORY DISTRESS SYNDROME BY NATURAL KILLER T CELLS.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. We established a LPS-induced lung injury mouse model. We used genetically engineered mice to investigate the relationship among the IL-33/ST2 axis, NKT cells, and ARDS. We found that IL-33 was localized to the nucleus in alveolar epithelial cells, from which it was released 1 h after ARDS induction in wild-type (WT) mice. Mice lacking IL-33 (IL-33 - / - ) or ST2 (ST2 - / - ) exhibited reduced neutrophil infiltration, alveolar capillary leakage, and lung injury in ARDS compared with WT mice. This protection was associated with decreased lung recruitment and activation of invariant nature killer (iNKT) cells and activation of traditional T cells. Then, we validated that iNKT cells were deleterious in ARDS in CD1d - / - and Vα14Τg mice. Compared with WT mice, Vα14Τg mice exhibited increased lung injury in ARDS, and the CD1d - / - mice showed outcomes opposite those of the Vα14Τg mice. Furthermore, we administered a neutralizing anti-ST2 antibody to LPS-treated WT and Vα14Τg mice 1 h before LPS administration. We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.

A bibliometric and visual analysis of low carbohydrate diet.

Introduction: Numerous studies have confirmed the effects of low carbohydrate diet (LChD) on metabolism and chronic diseases. However, there were no bibliometric studies on LChD. This study was conducted through a bibliometric analysis to investigate the current status, hotspots and frontiers trends. Methods: We searched all research publications related to LChD from 2002 to 2021 on the Web of Scientific Core Collection (WoSCC). CiteSpace and VOSviewer software was used to analyze countries/regions, institutions, journals, authors, references, and keywords. Results: A total of 6938 papers were included, with an increasing trend of annual publication. LChD categories mainly included nutrition, endocrinology, and neurosciences which reflected the interdisciplinary characteristics. USA was with the largest number and the world science center in LChD field. Universities were main research institutions and five of the top 10 institutions were from USA. Eric Heath Kossoff had 101 publications and ranked first. Nutrients was the leading journal. "A randomized trial of a low-carbohydrate diet for obesity" and "Obesity" were considered to be the most co-cited and cited reference respectively. The hotspots of LChD are four aspects, "ketogenic diet", "metabolism disease", "cardiovascular disease" and "cancer". We summarized that "oxidative stress", "gut microbiota", and "inflammation factors" are becoming frontiers trends of LChD research in the future and deserve further study. Discussion: Over the past 20 years research on LChD has gained great attention. To better explore LChD field, multilevel mechanism studies will be required in the future.

Burkholderia gladioli strain KJ-34 exhibits broad-spectrum antifungal activity.

Introduction: Plant pathogens are one of the major constraints on worldwide food production. The antibiotic properties of microbes identified as effective in managing plant pathogens are well documented. Methods: Here, we used antagonism experiments and untargeted metabolomics to isolate the potentially antifungal molecules produced by KJ-34. Results: KJ-34 is a potential biocontrol bacterium isolated from the rhizosphere soil of rice and can fight multiple fungal pathogens (i.e. Ustilaginoidea virens, Alternaria solani, Fusarium oxysporum, Phytophthora capsica, Corynespora cassiicola). The favoured fermentation conditions are determined and the fermentation broth treatment can significantly inhibit the infection of Magnaporthe oryzae and Botryis cinerea. The fermentation broth suppression ratio is 75% and 82%, respectively. Fermentation broth treatment disrupted the spore germination and led to malformation of hyphae. Additionally, we found that the molecular weight of antifungal products were less than 1000 Da through semipermeable membranes on solid medium assay. To search the potentially antifungal molecules that produce by KJ-34, we used comparative and bioinformatics analyses of fermentation broth before and after optimization by mass spectrometry. Untargeted metabolomics analyses are presumed to have a library of antifungal agents including benzoylstaurosporine, morellin and scopolamine. Discussion: These results suggest that KJ-34 produced various biological control agents to suppress multiple phytopathogenic fungi and showed a strong potential in the ecological technologies of prevention and protection.