Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

Multimorbidity and associated informal care receiving characteristics for US older adults: a latent class analysis.

BACKGROUND: Older adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes. METHODS: Data are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership. RESULTS: A four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05-1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05-2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29-3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19-0.77). CONCLUSIONS: Results highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care.

Establishment of a prognostic model to predict chemotherapy response and identification of RAC3 as a chemotherapeutic target in bladder cancer.

Cisplatin-based chemotherapy is considered the primary treatment option for patients with advanced bladder cancer (BCa). However, the objective response rate to chemotherapy is often unsatisfactory, leading to a poor 5-year survival rate. Furthermore, current strategies for evaluating chemotherapy response and prognosis are limited and inefficient. In this study, we aimed to address these challenges by establishing a chemotherapy response type gene (CRTG) signature consisting of 9 genes and verified the prognostic value of this signature using TCGA and GEO BCa cohorts. The risk scores based on the CRTG signature were found to be associated with advanced clinicopathological status and demonstrated favorable predictive power for chemotherapy response in the TCGA cohort. Meanwhile, tumors with high risk scores exhibited a tendency toward a "cold tumor" phenotype. These tumors showed a low abundance of T cells, CD8+ T cells and cytotoxic lymphocytes, along with a high abundance of cancer-associated fibroblasts. Moreover, they displayed higher mRNA levels of these immune checkpoints: CD200, CD276, CD44, NRP1, PDCD1LG2 (PD-L2), and TNFSF9. Furthermore, we developed a nomogram that integrated the CRTG signature with clinicopathologic risk factors. This nomogram proved to be a more effective tool for predicting the prognosis of BCa patients. Additionally, we identified Rac family small GTPase 3 (RAC3) as a biomarker in our model. RAC3 was found to be overexpressed in chemoresistant BCa tissues and enhance the chemotherapeutic resistance of BCa cells in vitro and in vivo by regulating the PAK1-ERK1/2 pathway. In conclusion, our study presents a novel CRTG model for predicting chemotherapy response and prognosis in BCa. We also highlight the potential of combining chemotherapy with immunotherapy as a promising strategy for chemoresistant BCa and that RAC3 might be a latent target for therapeutic intervention.

Measurement plane of the cross-sectional area of the masseter muscle in patients with skeletal Class III malocclusion: An artificial intelligence model.

INTRODUCTION: This study aimed to determine a measurement plane that could represent the maximum cross-sectional area (MCSA) of masseter muscle using an artificial intelligence model for patients with skeletal Class III malocclusion. METHODS: The study included 197 patients, divided into subgroups according to sex, mandibular symmetry, and mandibular plane angle. The volume, MCSA, and the cross-sectional area (CSA) at different levels were calculated automatically. The vertical distance between MCSA and mandibular foramen, along with the ratio of the masseter CSA at different levels to the MCSA (R), were also calculated. RESULTS: The MCSA and volume showed a strong correlation in the total sample and each subgroup (P <0.001). The correlation between the CSA at each level and MCSA was statistically significant (P <0.001). The peak of the r and the correlation coefficient between the CSA at different levels and MCSA were mostly present 5-10 mm above the mandibular foramen for the total sample and the subgroups. The mean of RA5 to RA10 was >0.93, whereas the corresponding correlation coefficient was >0.96, both for the entire sample and for the subgroups. CONCLUSIONS: MCSA could be used as an indicator for masseter muscle size. For patients with skeletal Class III malocclusion, the CSA 5-10 mm above the mandibular foramen, parallel to the Frankfort plane, could be used to estimate the masseter muscle MCSA.

Changes in masseter muscle morphology after surgical-orthodontic treatment in patients with skeletal Class III malocclusion with mandibular asymmetry: The automatic masseter muscle segmentation model.

INTRODUCTION: This study evaluated the masseter muscle changes after surgical-orthodontic treatment in patients with a skeletal Class III malocclusion using automatic segmentation. METHODS: Images of 120 patients with skeletal Class III malocclusion were obtained and reconstructed at T0 (pretreatment), T1 (presurgery), and T2 (6-12-month postsurgery). The patients were divided into symmetrical and asymmetrical groups. The volume, major axis length, maximum cross-sectional area, horizontal cross-sectional area 5 mm above the mandibular foramen (CSAF), and orientation were calculated automatically. RESULTS: In the asymmetrical group, the volume and major axis length on the deviated side were lower than on the nondeviated side at T0, T1, and T2 (P <0.05). There were no significant differences in maximum cross-sectional area and CSAF bilaterally. The orientation was coronally more vertical and sagittally more forward on the deviated side (both P <0.001). In the symmetrical group, there were no significant bilateral differences at T0, T1, and T2. The volume, major axis length, and CSAF decreased, and the coronal orientation was more vertical on the nondeviated side at T2 than at T0 in both groups (P <0.05). The coronal plane orientation was more inclined on the deviated side at T2 than at T0 in the asymmetrical group (P <0.05). CONCLUSIONS: The smaller volume on the deviated side at T2 indicates the need for myofunctional training after surgery. The masseter muscle volume and the cross-sectional area did not recover to the preorthodontic levels. Studies with longer follow-up durations are needed to confirm these findings.

Inter-relationships of galectin-3 and NLR family pyrin domain containing 3 inflammasomes with oral lichen planus: a preliminary cross-sectional in vitro study.

BACKGROUND: The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to be highly expressed in oral lesions with the potential for malignant development such as oral lichen planus (OLP). And the NLRP3 inflammasome can be activated by galectin-3 (Gal-3) in immune-mediated chronic inflammatory diseases. This study aimed to explore the inter-relationships among Gal-3, NLRP3 inflammasome, and OLP. METHODS: A cross-sectional analysis of oral biopsy specimens from 30 patients with Erosive OLP and 30 healthy controls was performed. Immunohistochemical staining was used to evaluate the expression of Gal-3 and NLRP3 inflammasome. Two-sample t-test and Pearson correlation test were applied to analyze the data. RESULTS: Erosive OLP patients had significantly higher Gal-3 levels compared with controls (p < 0.0001). A similar pattern emerged for NLRP3 inflammasome. In the overall sample, a positive correlation was observed between Gal-3 and NLRP3 (r = 0.92, p < 0.01). CONCLUSIONS: Patients with Erosive OLP lesions showed increased protein expression levels of Gal-3. A positive correlation was observed between Gal-3 and NLRP3 inflammasome.

Effects of preoperative albumin-to-globulin ratio on overall survival and quality of life in esophageal cell squamous carcinoma patients: a prospective cohort study.

OBJECTIVE: This study aimed to investigate the effect of preoperative albumin-to-globulin ratio (AGR) on overall survival (OS) and health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Serum albumin and globulin were measured within one week before surgery. Multiple follow-ups were conducted among patients with ESCC in the study in order to assess their life quality. The method used in the study was a telephone interview. Quality of life was measured using the EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and Esophageal Cancer Module (EORTC QLQ- OES18). RESULTS: A total of 571 ESCC patients were included in the study. The results illustrated that 5-year OS of high AGR group (74.3%) was better than the low one (62.3%) (P = 0.0068). Univariate and multivariate Cox regression analysis found that preoperative AGR (HR = 0.642, 95%CI: 0.444-0.927) are prognostic factor for patients with ESCC after surgery. In terms of quality of life, found that low AGR associated with increased postoperative time to deterioration (TTD) events in ESCC patients, and compared to low AGR, high AGR could delay the deterioration of emotional functioning(P = 0.001), dysphagia(P = 0.033), trouble with taste(P = 0.043) and speech problems(P = 0.043). After using the multivariate Cox regression analysis showed that high AGR could improve patients' emotional function (HR = 0.657, 95% CI: 0.507-0.852) and trouble with taste (HR = 0.706, 95% CI: 0.514-0.971). CONCLUSIONS: Preoperative AGR in patients with ESCC after esophagectomy was positively correlated with overall survival rate and quality of life after operation.

Balance telerehabilitation and wearable technology for people with Parkinson's disease (TelePD trial).

BACKGROUND: Balance impairments, that lead to falls, are one of the main symptoms of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days. METHODS: The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period. CONCLUSION: The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments. TRIAL REGISTRATION: This trial was prospectively registered on ClinicalTrials.gov (NCT05680597).

Overexpression of Zostera japonica J protein gene ZjDjB1 in Arabidopsis enhanced the tolerance to lead stress.

BACKGROUND: Among the heavy metal pollution in soil, lead pollution is particularly prominent. The lead in contaminated soil will not only cause damage to plants, animals and microorganisms, but also seriously affect the progress of the entire ecosystem. Under lead stress, the abundance of DnaJ protein in plants will increase. However, little is known about the role of DnaJ in lead stress. METHODS AND RESULTS: We used transgenic Arabidopsis that overexpressed DnaJ gene ZjDjB1 of Zostera japonica as material to study the role of DnaJ in the mechanism of lead induced stress response. Under lead stress, the seedlings and adult plants of transgenic ZjDjB1 Arabidopsis have higher tolerance to lead stress than wild type. Under lead stress, the content of NO and O2·- free radicals in transgenic ZjDjB1 Arabidopsis was lower than that of wild type. The negative effect of catalase in transgenic ZjDjB1 Arabidopsis under lead stress was weaker than that of wild type. The expression of ABC transporter of mitochondrion 3 (ATM3; systematic name: ABCB25) in transgenic ZjDjB1 Arabidopsis under lead stress was higher than that in wild type. CONCLUSIONS: These results confirmed that ZjDjB1, the DnaJ gene of Z. japonica, was involved in the reaction mechanism to lead pollution, which might improve the tolerance of plants to lead stress by maintaining catalase activity and increasing the expression level of ATM3 under lead stress.

A sensitive and rapid electrochemical biosensor for sEV-miRNA detection based on domino-type localized catalytic hairpin assembly.

Small extracellular-vesicule-associated microRNA (sEV-miRNA) is an important biomarker for cancer diagnosis. However, rapid and sensitive detection of low-abundance sEV-miRNA in clinical samples is challenging. Herein, a simple electrochemical biosensor that uses a DNA nanowire to localize catalytic hairpin assembly (CHA), also called domino-type localized catalytic hairpin assembly (DT-LCHA), has been proposed for sEV-miRNA1246 detection. The DT-LCHA offers triple amplification, (i). CHA system was localized in DNA nanowire, which shorten the distance between hairpin substrate, inducing the high collision efficiency of H1 and H2 and domino effect. Then, larger numbers of CHAs were triggered, capture probe bind DT-LCHA by exposed c sites. (ii) The DNA nanowire can load large number of electroactive substance RuHex as amplified electrochemical signal tags. (iii) multiple DT-LCHA was carried by the DNA nanowire, only one CHA was triggered, the DNA nanowire was trapped by the capture probe, which greatly improve the detection sensitivity, especially when the target concentration is extremely low. Owing to the triple signal amplification in this strategy, sEV-miRNA at a concentration of as low as 24.55 aM can be detected in 20 min with good specificity. The accuracy of the measurements was also confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, the platform showed good performance in discriminating healthy donors from patients with early gastric cancer (area under the curve [AUC]: 0.96) and was equally able to discriminate between benign gastric tumors and early cancers (AUC: 0.77). Thus, the platform has substantial potential in biosensing and clinical diagnosis.

Relation Between Cognitive Assessment and Clinical Physical Performance Measures After Mild Traumatic Brain Injury.

OBJECTIVES: To investigate the relation between cognitive and motor performance in individuals with mild traumatic brain injury (mTBI) and examine differences in both cognitive and motor performance between adults after mTBI and healthy controls. DESIGN: Multi-center, cross-sectional study. SETTING: Three institutional sites (Courage Kenny Research Center, Minneapolis, MN, Oregon Health & Science University, Portland, OR, and University of Utah, Salt Lake City, UT). PARTICIPANTS: Data were collected from 110 participants (N=110), including those with mTBI and healthy controls, who completed cognitive and physical performance assessments. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Cognitive assessments involved the Automated Neuropsychological Assessment Metrics to evaluate domains of attention, memory, reaction time, processing speed, and executive function. Physical performance was evaluated through clinical performance assessments, such as the 1-min walk test, the modified Illinois Agility Test, the Functional Gait Assessment Tool, the High-Level Mobility Assessment Tool, a complex turning course, and a 4-Item Hybrid Assessment of Mobility for mTBI. Participants also completed additional trials of the 1-min walk test, modified Illinois Agility Test, and complex turning course with a simultaneous cognitive task. RESULTS: Individuals with mTBI performed worse on cognitive assessments, as well as several of the physical performance assessments compared with healthy controls. Complex tasks were more strongly related to cognitive assessments compared with simple walking tasks. CONCLUSIONS: Combining complex motor tasks with cognitive demands may better demonstrate functional performance in individuals recovering from mTBI. By understanding the relation between cognitive and physical performance in individuals recovering from mTBI, clinicians may be able to improve clinical care and assist in return to activity decision-making.

Modeling soybean cultivation suitability in China and its future trends in climate change scenarios.

Soybean is an important source of oil and vegetable protein and plays a key role in agricultural production and economy. A suitability evaluation of soybean cultivation is important for identifying potential soybean planting areas. Based on the raster data of soybean harvest ratio (FSHA) and climate-soil-topography-socio-economy environmental factors, we used MaxEnt to simulate the soybean planting suitability and potential distribution in China and the future trends of soybean cultivation under climate change. Three shared socio-economic paths (SSPs) that set up in the future climate section were considered, including SSP126 (sustainable path), SSP245 (intermediate path), and SSP585 (fossil fuel dominated development path). The result shows that the suitability of soybean cultivation was primarily influenced by elevation, precipitation of warmest quarter, capacity of the clay fraction, slope, portion of primary industry, topsoil gravel content, mean diurnal temperature range and accumulated temperature ≥10 °C. High-suitability and moderate-suitability area are respectively 26.51 Mha and 41.93 Mha in China. High-suitability areas for soybean are mainly concentrated in the Northeast Plain, the North China Plain and the northern parts of the middle and lower Yangtze River plain. There were many provinces with high soybean planting potential but low development degrees, including Hebei, Henan, Shandong, Tianjin, Jilin, Liaoning, Jiangsu, Hubei and Shaanxi. From 2021 to 2060, the total area highly and moderately suitable for soybean cultivation is projected to increase first and then decrease under both SSP126 and SSP245 scenarios. However, it shows a continued upward trend under SSP585, the rising part accounting for more than 10% in the base of historical data. Specifically, under SSP585, the suitability grade in most parts of Northeast China (eastern Inner Mongolia, northern Heilongjiang and western Jilin and Liaoning) will have a general promotion, opposite to the result under SSP126. Moreover, parts of southwest China (Yunnan, Chongqing, northern Guizhou and eastern Sichuan) may be more suitable for soybean cultivation in both scenarios. This study provides a practical reference for current and future soybean planting layout and relative countermeasures.

Validation of the Asia-Pacific colorectal screening score and its modified versions in predicting colorectal advanced neoplasia in Chinese population.

BACKGROUND: Colorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score. METHODS: We conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN). RESULTS: 1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P < 0.05), and the RR (95%C.I.) ranged 2.20 (1.50-3.22) [8-point risk] to 4.00 (2.41-6.65) [Modified APCS]. The c-statistics (95%C.I.) of the scoring systems ranged from 0.58 (0.53-0.62) [8-point risk] to 0.65 (0.61-0.69) [KCS]. The sensitivity (95%C.I.) of these systems ranged from 31.25 (22.83-40.70) [8-point risk] to 84.82 (76.81-90.90) [Modified APCS], while the specificity (95%C.I.) ranged from 43.50 (41.12-45.90) [Modified APCS] to 83.81 (81.96-85.53) [8-point risk]. Using the APCS scoring system as a comparator, the net reclassification improvement (NRI) of each modified version ranged from - 10.34% (95%C.I.: - 22.63 to 1.95%) [8-point risk] to 4.79% (95%C.I.: - 1.50% to 11.08) [KCS]. The colonoscopy resource load (95%C.I.) ranged from 9 [1-3] [8-point risk] to 11 [3-5] [APCS and Modified APCS]. CONCLUSIONS: The APCS score and its modified versions have certain ability to predict the risk of advanced neoplasia and reduce the resource load. The modified APCS score and the KCS score seemed the preferable systems to classify high risk subjects based on its high RR, sensitivity and predictive ability in the selected population. Future research could focus on adding risk factors or combining with laboratory test results to improve the predictive power of the scoring system.

14-3-3 gene of Zostera japonica ZjGRF1 participates in gibberellin signaling pathway.

BACKGROUND: Zostera japonica is a unique seagrass species in Asia with important ecological value. Gibberellin (GA) is a plant hormone crucial in the regulation of plant growth and development, including seed longevity, seed germination, anti-aging, hypocotyl elongation, leaf development, reproductive organ development, and abiotic stress responses. However, the role of 14-3-3 gene of Z. japonica in GA signaling pathway remains unclear. METHODS AND RESULTS: Herein, gibberellin content and expression of GA synthesis genes were lower in Arabidopsis overexpressing ZjGRF1, 14-3-3 gene of Z. japonica, than in wild type (WT). Moreover, the expression level of GA receptors was lower in transgenic ZjGRF1 Arabidopsis than in WT. The expression level of GA response gene expansin8 (EXP8) was lower in transgenic ZjGRF1 Arabidopsis than in WT. In contrast, the expression levels of PACLOBUTRAZOL RESISTANT1 (PRE1), PRE5 and SCARECROW-LIKE 3 (SCL3) were higher in the transgenic ZjGRF1 Arabidopsis than in WT. Transgenic ZjGRF1 Arabidopsis has decreased sensitivity to paclobutrazol, an inhibitor of GA synthesis. The expression level of flowering regulatory genes was lower in transgenic ZjGRF1 Arabidopsis than in WT. CONCLUSION: This is the first study to report the function of 14-3-3 gene family in seagrass. These findings can be used in future studies on the regulation role of 14-3-3 gene on plant development.

Overexpression of Zostera japonica heat shock protein gene ZjHsp70 enhances the thermotolerance of transgenic Arabidopsis.

BACKGROUND: Heat shock protein 70s (Hsp70s) are major members of the heat shock protein family and play a variety of roles to protect plants against stress. Plant Hsp70s are a conserved and widely expressed family of heat shock proteins. They have two main functional regions: N-terminal nucleic acid binding region and C-terminal substrate binding region. METHODS AND RESULTS: In this study, we cloned the Hsp70 gene of Zostera japonica (ZjHsp70) based on the sequence obtained by transcriptome sequencing. The transcriptional levels of ZjHsp70 increased significantly at 1 h after heat treatment. ZjHsp70 was located in the cytoplasm and nucleus. The overexpression of ZjHsp70 in Arabidopsis resulted in increased heat tolerance, lower contents of malondialdehyde and higher antioxidant enzyme activity than in the wild type. ZjHsp70 may achieve this goal by maintaining highly active antioxidant enzymes. CONCLUSIONS: We show that ZjHsp70 can improve plant heat tolerance by maintaining high antioxidant enzyme activity under high temperature stress. This study provided a basis to study the role of ZjHsp70 in thermotolerance in more detail.

Overexpression of Zostera japonica 14-3-3 gene ZjGRF1 enhances the resistance of transgenic Arabidopsis to copper stress.

BACKGROUND: Copper is both a nutrient essential for plant growth and a pollutant. In recent decades, with the rapid development of industrial and agricultural production, copper has been used more and more widely, and its consumption has also increased rapidly. Excessive soil copper contents induce phytotoxicity, affecting plant growth, development and yields. Moreover, copper can accumulate in crops and enter the food chain through enrichment, harming human health. METHODS AND RESULTS: In this study, Arabidopsis wild-type (WT) and Zostera japonica 14-3-3 gene ZjGRF1 overexpression lines were used to explore the physiological function and molecular mechanism of ZjGRF1 in Arabidopsis in the copper stress response. Under copper stress, compared with WT plants, transgenic ZjGRF1 Arabidopsis plants exhibited less inhibition of root growth and development and had higher fresh weights. Under copper stress, the soluble sugar and soluble protein contents in transgenic ZjGRF1 Arabidopsis plants were significantly higher than those in WT plants, while the superoxide dismutase (SOD), peroxidase and catalase (CAT) activities were significantly higher than those in WT plants. Additionally, the malonaldehyde content of transgenic plants was significantly lower than that of WT plants. Furthermore, qRT-PCR results showed that under copper stress, the SOD, CAT1 and HMA5 expression levels in transgenic ZjGRF1 Arabidopsis plants were significantly higher than those in WT plants, while COPT1 expression was significantly lower than that in WT plants. CONCLUSIONS: ZjGRF1 enhanced the copper stress resistance of Arabidopsis by maintaining high antioxidant enzyme activity, increasing copper efflux and reducing copper uptake under copper stress.

Caveolin-1 Regulation and Function in Mouse Uterus during Early Pregnancy and under Human In Vitro Decidualization.

Decidualization is essential to rodent and primate pregnancy. Senescence is increased during decidualization. Failure of senescence clearance during decidualization will cause pregnancy abnormality. Caveolin-1 is located in plasmalemmal caveolae and involved in senescence. However, whether caveolin-1 is involved in decidualization remains undefined. In this study, we examined the expression, regulation and function of Caveolin-1 during mouse early pregnancy and under mouse and human in vitro decidualization. From days 1 to 8 of pregnancy, Caveolin-1 signals are mainly located in endothelium and myometrium. Estrogen stimulates Caveolin-1 expression in endothelium. Deficiency of estrogen receptor α significantly promotes Caveolin-1 level in uterine stromal cells. Progesterone upregulates Caveolin-1 expression in luminal epithelium. During mouse in vitro decidualization, Caveolin-1 is significantly increased. However, Caveolin-1 is obviously decreased during human in vitro decidualization. Caveolin-1 overexpression and siRNA suppress and upregulate IGFBP1 expression under in vitro decidualization, respectively. Blastocysts-derived tumor necrosis factor α (TNFα) and human Chorionic Gonadotropin (hCG) regulate Caveolin-1 in mouse and human decidual cells, respectively. Caveolin-1 levels are also regulated by high glucose and insulin. In conclusion, a low level of Caveolin-1 should be beneficial for human decidualization.

Primary Cilia Restrain PI3K-AKT Signaling to Orchestrate Human Decidualization.

Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFß, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.

Female reproductive abnormalities in mouse adolescent pregnancy.

There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.

Effects of Aurora kinase A on mouse decidualization via Stat3-plk1-cdk1 pathway.

BACKGROUND: Decidualization is essential to the successful pregnancy in mice. The molecular mechanisms and effects of Aurora kinase A (Aurora A) remain poorly understood during pregnancy. This study is the first to investigate the expression and role of Aurora A during mouse decidualization. METHODS: Quantitative real time polymerase chain reaction, western blotting and in situ hybridization were used to determine the expression of Aurora A in mouse uteri. Aurora A activity was inhibited by Aurora A inhibitor to explore the role of Aurora A on decidualization via regulating the Aurora A/Stat3/Plk1/Cdk1 signaling pathway. RESULTS: Aurora A was strongly expressed at implantation sites compared with inter-implantation sites. Furthermore, Aurora A was also significantly increased in oil-induced deciduoma compared with control. Both Aurora A mRNA and protein were significantly increased under in vitro decidualization. Under in vitro decidualization, Prl8a2, a marker of mouse decidualization, was significantly decreased by TC-S 7010, an Aurora A inhibitor. Additionally, Prl8a2 was reduced by Stat3 inhibitor, Plk1 inhibitor and Cdk1 inhibitor, respectively. Moreover, the protein levels of p-Stat3, p-Plk1 and p-Cdk1 were suppressed by TC-S 7010. The protein levels of p-Stat3, p-Plk1 and p-Cdk1 were also suppressed by S3I-201, a Stat3 inhibitor). SBE 13 HCl (Plk1 inhibitor) could reduce the protein levels of p-Plk1 and p-Cdk1. Collectively, Aurora A could regulate Stat3/Plk1/Cdk1 signaling pathway. CONCLUSION: Our study shows that Aurora A is expressed in decidual cells and should be important for mouse decidualization. Aurora A/Stat3/Plk1/Cdk1 signaling pathway may be involved in mouse decidualization.