Identification of core subunits of photosystem II as action sites of HSP21, which is activated by the GUN5-mediated retrograde pathway in Arabidopsis.

Photosystem II (PSII) is the most thermolabile photosynthetic complex. Physiological evidence suggests that the small chloroplast heat-shock protein 21 (HSP21) is involved in plant thermotolerance, but the molecular mechanism of its action remains largely unknown. Here, we have provided genetic and biochemical evidence that HSP21 is activated by the GUN5-dependent retrograde signaling pathway, and stabilizes PSII by directly binding to its core subunits such as D1 and D2 proteins under heat stress. We further demonstrate that the constitutive expression of HSP21 sufficiently rescues the thermosensitive stability of PSII and survival defects of the gun5 mutant with dramatically improving granal stacking under heat stress, indicating that HSP21 is a key chaperone protein in maintaining the integrity of the thylakoid membrane system under heat stress. In line with our interpretation based on several lines of in vitro and in vivo protein-interaction evidence that HSP21 interacts with core subunits of PSII, the kinetics of HSP21 binding to the D1 and D2 proteins was determined by performing an analysis of microscale thermophoresis. Considering the major role of HSP21 in protecting the core subunits of PSII from thermal damage, its heat-responsive activation via the heat-shock transcription factor HsfA2 is critical for the survival of plants under heat stress. Our findings reveal an auto-adaptation loop pathway that plant cells optimize particular needs of chloroplasts in stabilizing photosynthetic complexes by relaying the GUN5-dependent plastid signal(s) to activate the heat-responsive expression of HSP21 in the nucleus during adaptation to heat stress in plants.

Metabolic Reprogramming in Chloroplasts under Heat Stress in Plants.

Increases in ambient temperatures have been a severe threat to crop production in many countries around the world under climate change. Chloroplasts serve as metabolic centers and play a key role in physiological adaptive processes to heat stress. In addition to expressing heat shock proteins that protect proteins from heat-induced damage, metabolic reprogramming occurs during adaptive physiological processes in chloroplasts. Heat stress leads to inhibition of plant photosynthetic activity by damaging key components functioning in a variety of metabolic processes, with concomitant reductions in biomass production and crop yield. In this review article, we will focus on events through extensive and transient metabolic reprogramming in response to heat stress, which included chlorophyll breakdown, generation of reactive oxygen species (ROS), antioxidant defense, protein turnover, and metabolic alterations with carbon assimilation. Such diverse metabolic reprogramming in chloroplasts is required for systemic acquired acclimation to heat stress in plants.

Corrigendum to "Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients" [Heliyon 10(3), January 2024, e24798].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e24798.].

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

Association between the oxidative balance score and thyroid function: Results from the NHANES 2007-2012 and Mendelian randomization study.

BACKGROUND: Oxidative stress is a significant contributor to the development of various diseases, and the oxidative balance score (OBS) is a valuable tool for assessing the impact of dietary and lifestyle factors on oxidative stress in humans. Nevertheless, the precise relationship between OBS and thyroid function in adults remains elusive. METHODS: This cross-sectional study comprised 6222 adult participants drawn from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012. Employing weighted multivariable linear regression modeling, the study estimated the connection between OBS quartiles and thyroid functions. The causal relationship between OBS components and thyroid function was analyzed by Mendelian randomization (MR). RESULTS: We found a significant negative correlation between OBS and free thyroxine (FT4) and total thyroxine (TT4). Univariate and multivariate MR Analyses showed a causal relationship between BMI and FT4. Copper, smoking, and riboflavin showed a causal relationship with FT4 after moderation. CONCLUSION: We found that a lifestyle high in antioxidant exposure reduced FT4 and TT4 levels in the population. We suggest that BMI, Copper, and Riboflavin are important factors in the regulation of FT4 levels.

Clinical Analysis of Y Chromosome Microdeletions and Chromosomal Aberrations in 1596 Male Infertility Patients of the Zhuang Ethnic Group in Guangxi.

The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanning between January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 male infertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group (P < 0.001). Of all types of YCM, the highest detection rate was AZFc (n = 83), followed by AZFb + c (n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY (n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant (P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.

Highly expressed miR-144-3p promotes the proliferation, migration and invasion of colon carcinoma cells by activating the Wnt/ß-catenin signaling pathway through targeting SFRP1.

Background: To investigate the influence of miR-144-3p on the proliferation, migration and invasion of colon carcinoma by targeting secreted frizzled-related protein 1 (SFRP1) as well as of the Wnt/ß-catenin signaling pathway. Methods: Based on the TCGA database, the association between the expression of miR-144-3p and the clinical information and prognosis of patients with colon carcinoma was examined, and SFRP1 was selected as the target gene for further studies based on bioinformatics prediction tools. CCK8 assay, wound healing assay and transwell invasion assay were employed to examine the impact of miR-144-3p on colon carcinoma cells. The regulation of SFRP1 by miR-144-3p was investigated using a dual-luciferase reporter system, and a rescue experiment was conducted to further elucidate whether miR-144-3p promotes the migration of colon carcinoma cells through targeting SFRP1 or not. The Wnt/ß-catenin signaling pathway-mediated effect of miR-144-3p in colon carcinoma was finally validated through the targeting of SFRP1. Results: The bioinformatics analysis showed that the miR-144 expression levels were substantially greater in colon carcinoma tissue than in para-carcinoma tissue and were closely with clinical stage and prognosis. The findings obtained from the trial indicated that miR-144-3p substantially expressed in colon carcinoma tissue sample and the colon carcinoma cells, and the overexpressed miR-144-3p boosted the colon carcinoma cells' proliferation, migration and invasion. The results of dual-luciferase reporter gene assay revealed that miR-144-3p targeted SFRP1, and rescue experiment was carried out and its results indicated that miR-144-3p increased colon carcinoma cells' migration through targeting SFRP1. In addition, the molecular axis of miR-144-3p/SFRP1 may over-activate the Wnt/ß-catenin signaling pathway. Conclusions: The present study has identified a novel malignant biological behavior, namely the ability of miR-144-3p to enhance the proliferation, migration and invasion of colon carcinoma cells by targeting SFRP1 and activating the Wnt/ß-catenin signaling pathway. Consequently, miR-144-3p emerges as a promising diagnostic and therapeutic target for colon carcinoma.

A nitric oxide burst at the shoot apex triggers a heat-responsive pathway in Arabidopsis.

When confronted with heat stress, plants depend on the timely activation of cellular defences to survive by perceiving the rising temperature. However, how plants sense heat at the whole-plant level has remained unanswered. Here we demonstrate that shoot apical nitric oxide (NO) bursting under heat stress as a signal triggers cellular heat responses at the whole-plant level on the basis of our studies mainly using live-imaging of transgenic plants harbouring pHsfA2::LUC, micrografting, NO accumulation mutants and liquid chromatography-tandem mass spectrometry analysis in Arabidopsis. Furthermore, we validate that S-nitrosylation of the trihelix transcription factor GT-1 by S-nitrosoglutathione promotes its binding to NO-responsive elements in the HsfA2 promoter and that loss of function of GT-1 disrupts the activation of HsfA2 and heat tolerance, revealing that GT-1 is the long-sought mediator linking signal perception to the activation of cellular heat responses. These findings uncover a heat-responsive mechanism that determines the timing and execution of cellular heat responses at the whole-plant level.

Frequency of autoimmune diseases in myasthenia gravis: a systematic review.

The course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%-14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and anti-acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Nuclear-encoded synthesis of the D1 subunit of photosystem II increases photosynthetic efficiency and crop yield.

In photosynthetic organisms, the photosystem II (PSII) complex is the primary target of thermal damage. Plants have evolved a repair process to prevent the accumulation of damaged PSII. The repair of PSII largely involves de novo synthesis of proteins, particularly the D1 subunit protein encoded by the chloroplast gene psbA. Here we report that the allotropic expression of the psbA complementary DNA driven by a heat-responsive promoter in the nuclear genome sufficiently protects PSII from severe loss of D1 protein and dramatically enhances survival rates of the transgenic plants of Arabidopsis, tobacco and rice under heat stress. Unexpectedly, we found that the nuclear origin supplementation of the D1 protein significantly stimulates transgenic plant growth by enhancing net CO2 assimilation rates with increases in biomass and grain yield. These findings represent a breakthrough in bioengineering plants to achieve efficient photosynthesis and increase crop productivity under normal and heat-stress conditions.