Insight into the regulatory mechanism of ß-arrestin2 and its emerging role in diseases.

ß-arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein-coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that ß-arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post-transcriptional modifications can affect the expression of ß-arrestin2. Furthermore, post-translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S-nitrosylation affect the cellular localization of ß-arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of ß-arrestin2. This review summarizes the structure and function of ß-arrestin2 and reveals the mechanisms involved in the regulation of ß-arrestin2 at multiple levels. Additionally, recent studies on the role of ß-arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting ß-arrestin2.

Prevalence of mental health symptoms and associated risk factors among healthcare workers in specialized COVID-19 hospitals in Anyang, China: A cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.

Occurrence and genotyping of Enterocytozoon bieneusi in flying squirrels (Trogopterus xanthipes) from China.

Enterocytozoon bieneusi is an obligate intracellular microsporidian parasite with a worldwide distribution. As a zoonotic pathogen, E. bieneusi can infect a wide range of wildlife hosts through the fecal-oral route. Although the feces of flying squirrels (Trogopterus xanthipes) are considered a traditional Chinese medicine (as "faeces trogopterori"), no literature is available on E. bieneusi infection in flying squirrels to date. In this study, a total of 340 fresh flying squirrel fecal specimens from two captive populations were collected in Pingdingshan city, China, to detect the prevalence of E. bieneusi and assess their zoonotic potential. By nested PCR amplification of the ITS gene, six specimens tested positive, with positive samples from each farm, with an overall low infection rate of 1.8%. The ITS sequences revealed three genotypes, including known genotype D and two novel genotypes, HNFS01 and HNFS02. Genotype HNFS01 was the most prevalent (4/6, 66.7%). Phylogenetic analysis showed that all genotypes clustered into zoonotic Group 1, with the novel genotypes clustering into different subgroups. To our knowledge, this is the first report of E. bieneusi infection in flying squirrels, suggesting that flying squirrels could act as a potential reservoir and zoonotic threat for E. bieneusi transmission to humans in China.

Title: Occurrence et génotypage d'Enterocytozoon bieneusi chez les écureuils volants (Trogopterus xanthipes) de Chine. Abstract: Enterocytozoon bieneusi est un parasite microsporidien intracellulaire obligatoire présent dans le monde entier. En tant qu'agent pathogène zoonotique, E. bieneusi peut infecter un large éventail d'hôtes sauvages par la voie fécale-orale. Bien que les excréments d'écureuils volants (Trogopterus xanthipes) soient considérés comme un ingrédient de médecine traditionnelle chinoise (comme « faeces trogopterori ¼), aucune littérature n'est disponible à ce jour sur l'infection par E. bieneusi chez les écureuils volants. Dans cette étude, un total de 340 spécimens fécaux frais d'écureuils volants provenant de deux populations captives ont été collectés dans la ville de Pingdingshan, en Chine, pour détecter la prévalence d'E. bieneusi et évaluer leur potentiel zoonotique. Par amplification PCR nichée du gène ITS, six échantillons se sont révélés positifs, avec des échantillons positifs dans chaque ferme, et un taux d'infection global faible, à 1,8 %. Les séquences ITS ont révélé trois génotypes, dont le génotype D connu et deux nouveaux génotypes, HNFS01 et HNFS02. Le génotype HNFS01 était le plus répandu (4/6, 66,7 %). L'analyse phylogénétique a montré que tous les génotypes se regroupaient dans le groupe zoonotique 1, les nouveaux génotypes se regroupant en différents sous-groupes. À notre connaissance, il s'agit du premier rapport d'infection par E. bieneusi chez des écureuils volants, ce qui suggère que les écureuils volants pourraient agir comme un réservoir potentiel et une menace zoonotique pour la transmission d'E. bieneusi aux humains en Chine.

Selenoprotein GPX3 is a novel prognostic indicator for stomach adenocarcinoma and brain low-grade gliomas: Evidence from an integrative pan-cancer analysis.

Background: The antioxidant enzyme GPX3 is a selenoprotein that transports selenium in blood and maintains its levels in peripheral tissues. Aberrant GPX3 expression is strongly linked to the development of some tumors. However, there is a scarcity of studies examining the pan-cancer expression patterns and prognostic relevance of GPX3. Methods: GPX3 expression levels in normal tissues and multiple tumors were analyzed using TCGA, CCLE, GTEx, UALCAN and HPA databases. Forest plots and KM survival curves were utilized to evaluate the correlation between GPX3 expression and the outcome of tumor patients. The prognostic value of GPX3 in LGG was assessed utilizing the CGGA datasets, and that in STAD was tested by TCGA and GEO databases. A nomogram was then constructed to predict OS in STAD using R software. Additionally, the impact of GPX3 on post-chemoradiotherapy OS in patients with LGG and STAD was evaluated using the KM method. The multiplicative interaction of GPX3 expression, chemotherapy and radiotherapy on STAD and LGG was analyzed using logistic regression models. The correlation of GPX3 with the immune infiltration, immune neoantigens and MMR genes were investigated in TCGA cohort. Results: GPX3 exhibited downregulation across 21 tumor types, including STAD, with its decreased expression significantly associated with improved OS, DFS, PFS and DSS. Conversely, in LGG, low levels of GPX3 expression were indicative of a poorer prognosis. Univariate and multivariate Cox models further identified GPX3 as an independent predictor of STAD, and a nomogram based on GPX3 expression and other independent factors showed high level of predictive accuracy. Moreover, low GPX3 expression and chemotherapy prolonged the survival of STAD. In LGG patients, chemoradiotherapy, GPX3 and chemotherapy, and GPX3 and chemoradiotherapy may improve prognosis. Our observations reveal a notable connection between GPX3 and immune infiltration, immune neoantigens, and MMR genes. Conclusions: The variations in GPX3 expression are linked to the controlling tumor development and could act as a promising biomarker that impacts the prognosis of specific cancers like STAD and LGG.

Molecular detection of piroplasms in domestic donkeys in Xinjiang, China.

BACKGROUND: Piroplasmosis is a common and prevalent tick-borne disease that affects equids. OBJECTIVES: To determine the infection and molecular characteristics of the piroplasms in donkeys from Xinjiang, northwestern China, we undertook a cross sectional study by collecting representative samples across several counties within the region. METHODS: A total of 344 blood samples were collected from adult domestic donkeys from 13 counties in Xinjiang. PCR was conducted to test for T. equi and B. caballi in the blood samples based on the equine merozoite antigen-1 (Ema-1) gene and the 48 kDa rhoptry protein (BC48) gene, respectively. RESULTS: Sixteen blood samples tested positive for piroplasms and the overall infection rate was 4.7% (16/344). Seven of the 13 counties were positive for piroplasms. Among the 16 piroplasm-positive samples, 15 were singly infected with T. equi with an infection rate of 4.4% (15/344), and coinfection with T. equi and B. caballi was detected in one sample (0.3%, 1/344) from Wushi. Four T. equi sequence genotypes were identified and grouped into different branches of the evolutionary trees. CONCLUSION: These findings suggest that the infection rate of piroplasms is low in domestic donkeys in southern Xinjiang and that T. equi genotypes have a regional distribution.

Molecular detection of Cryptosporidium in Alpine musk deer (Moschus chrysogaster) in Gansu Province, Northwest China.

Cryptosporidium spp. are protozoa commonly found in domestic and wild animals. Limited information is available on Cryptosporidium in deer worldwide. In this study, 201 fecal samples were collected from Alpine musk deer on three farms in Gansu Province, China. Detection and subtyping of Cryptosporidium were performed by PCR and sequence analysis of the SSU rRNA and gp60 genes. The prevalence of Cryptosporidium infection in Alpine musk deer was 3.9% (8/201), with infection rates of 1.0% (1/100), 2.8% (1/36), and 9.2% (6/65) in three different farms. All positive samples for Cryptosporidium were from adult deer. Two Cryptosporidium species were identified, including C. parvum (n = 2) and C. xiaoi (n = 6). The C. parvum isolates were subtyped as IIdA15G1, while the C. xiaoi isolates were subtyped as XXIIIa (n = 2) and XXIIIg (n = 4). The IIdA15G1 subtype of C. parvum was found for the first time in deer. These results provide important insights into the identity and human infectious potential of Cryptosporidium in farmed Alpine musk deer.

Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

How does diagnosis-related group payment impact the health care received by rural residents? Lessons learned from China.

OBJECTIVES: There is growing evidence that differences exist between rural and urban residents in terms of health, access to care and the quality of health care received, especially in low- and middle-income countries (LMICs). To improve health equity and the performance of health systems, a diagnosis-related group (DRG) payment system has been introduced in many LMICs to reduce financial risk and improve the quality of health care. The aim of this study was to examine the impact of DRG payments on the health care received by rural residents in China, and to help policymakers identify and design implementation strategies for DRG payment systems for rural residents in LMICs. STUDY DESIGN: Health impact assessment. METHODS: This study compared the impact of DRG payments on the healthcare received by rural residents in China between the pre- and post-reform periods by applying a difference-in-difference (DID) methodology. The study population included individuals with three common conditions; namely, cerebral infarction, transient ischaemic attack (TIA), and vertebrobasilar insufficiency (VBI). Data on patient medical insurance type were assessed, and those who did not have rural insurance were excluded. RESULTS: This study included 13,088 patients. In total, 33.63% were from Guangdong (n = 4401), 38.21% were from Shandong (n = 5002), and 28.16% were from Guangxi (n = 3685). The DID results showed that the implementation of DRGs was positively associated with hospitalization expense (ß4 = 0.265, P = 0.000), treatment expense (ß4 = 0.343, P = 0.002), drug expense (ß4 = 0.607, P = 0.000), the spending of medical insurance funds (ß4 = 0.711, P = 0.000) and out-of-pocket costs (ß4 = 0.164, P = 0.000). CONCLUSIONS: The findings of this study suggest that the implementation of DRG payments increases health care costs and the financial burden on health systems and rural patients in LMICs. This is contrary to the original intention of implementing the DRG payment system.

Cryptosporidium spp. in large-scale sheep farms in China: prevalence and genetic diversity.

Cryptosporidium spp. are significant zoonotic intestinal parasites that induce diarrhea and even death across most vertebrates, including humans. Previous studies showed that sheep are important hosts for Cryptosporidium and that its distribution in sheep is influenced by geography, feeding patterns, age, and season. Environmental factors also influence the transmission of Cryptosporidium. Molecular studies of Cryptosporidium in sheep have been conducted in only a few regions of China, and studies into the effect of sheep-housing environments on Cryptosporidium transmission are even rarer. To detect the prevalence of Cryptosporidium in large-scale sheep-housing farms, a total of 1241 fecal samples were collected from sheep, 727 environmental samples were taken from sheep housing, and 30 water samples were collected in six regions of China. To ascertain the existence of the parasite and identify the species of Cryptosporidium spp., we conducted nested PCR amplification of DNA extracted from all samples using the small-subunit (SSU) rRNA gene as a target. For a more in-depth analysis of Cryptosporidium spp. subtypes, C. xiaoi-and C. ubiquitum-positive samples underwent separate nested PCR amplification targeting the 60 kDa glycoprotein (gp60) gene. The amplification of the Cryptosporidium spp. SSU rRNA gene locus from the whole genomic DNA of all samples yielded a positive rate of 1.2% (20/1241) in fecal samples, 0.1% (1/727) in environmental samples, and no positive samples were found in water samples. The prevalence of Cryptosporidium spp. infection in large-scale housed sheep was 1.7%, which was higher than that in free-ranging sheep (0.0%). The highest prevalence of infection was found in weaning lambs (6.8%). Among the different seasons, the peaks were found in the fall and winter. The most prevalent species were C. xiaoi and C. ubiquitum, with the former accounting for the majority of infections. The distribution of C. xiaoi subtypes was diverse, with XXIIIc (n = 1), XXIIId (n = 2), XXIIIe (n = 2), and XXIIIl (n = 4) identified. In contrast, only one subtype, XIIa (n = 9), was found in C. ubiquitum. In this study, C. xiaoi and C. ubiquitum were found to be the predominant species, and Cryptosporidium was found to be present in the environment. These findings provide an important foundation for the comprehensive prevention and management of Cryptosporidium in intensively reared sheep. Furthermore, by elucidating the prevalence of Cryptosporidium in sheep and its potential role in environmental transmission, this study deepens our understanding of the intricate interactions between animal health, environmental contamination, and public health dynamics.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Analysis of morphology, histology characteristics, and circadian clock gene expression of Onychostoma macrolepis at the overwintering period and the breeding period.

Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.

Precise Determination of Selenium Forms and Contents in Selenium-Enriched Rapeseed Seedlings and Flowering Stalks by HPLC-ICP-MS.

Rapeseed (Brassica napus L.) has the ability of selenium (Se) enrichment. Identification of selenides in Se-rich rapeseed products will promote the development and utilization of high value. By optimizing the Se species extraction process (protease type, extraction reagent, enzyme sample ratio, extraction time, etc.) and chromatographic column, an efficient, stable, and accurate method was established for the identification of Se species and content in rapeseed seedlings and flowering stalks, which were cultured by inorganic Se hydroponics. Five Se compounds, including selenocystine (SeCys2), methylselenocysteine (MeSeCys), selenomethionine (SeMet), selenite (SeIV), and selenate (SeVI) were qualitatively and quantitatively identified. Organoselenium was absolutely dominant in both seedlings and flowering stalks among the detected rapeseed varieties, with 64.18-90.20% and 94.38-98.47%, respectively. Further, MeSeCys, a highly active selenide, predominated in rapeseed flowering stalks with a proportion of 56.36-72.93% and a content of 1707.3-5030.3 µg/kg. This study provides a new source of MeSeCys supplementation for human Se fortification.

Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Mechanism of zinc stress on magnesium deficiency in rice plants (Oryza sativa L.): Insights from magnesium isotopes.

Magnesium (Mg) and zinc (Zn) are essential nutrients for plants. Mg deficiency often occurs in rice plants grown in Zn-polluted soil. However, the mechanism for this correlation is unclear. Here, we performed culture experiments on rice plants (Oryza sativa L.) and used Mg isotopes to investigate mechanisms of Zn stress on plant Mg deficiency. Our results show that excess Zn can significantly reduce the uptake of Mg in rice tissues. The root displays positive Δ26Mgplant-nutrient values (δ26Mgplant-δ26Mgnutrient; 1.90 ‰ to 2.06 ‰), which suggests that Mg enters the root cells mainly via Mg-specific transporters rather than non-selective diffusion. The decreased Δ26Mgplant-nutrient values with increasing Zn supply can be explained by the competition between Zn and Mg, both of which combine with same transporters in roots. In contrast, the shoots (stem and leaf) display much lower δ26Mg values than roots, which suggests that the transport of Mg from roots to aerial biomass is mainly via free Mg ions, during which Zn cannot competitively inhibit the movement of Mg. Our study suggests that the Mg deficiency in rice plants can be caused by high Zn-levels in soils and highlights the necessity of soil Zn-remediation in solving Mg deficiency problems in rice plants.

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3ß Signaling Pathway.

Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.

Microstructure evolution and the deformation mechanism in nanocrystalline superior-deformed tantalum.

The temperature-controlled relationship between the mechanical properties and deformation mechanism of tantalum (Ta) enables the extension of its application potential in various areas of life, including energy and electronics industries. In this work, the microstructure and deformation behavior of nanocrystalline superior-deformed Ta have been investigated in a wide temperature range. The structural analysis revealed that the high-performance Ta consists of several different substructures, with an average size of about 20 nm. The tensile behavior of nanocrystalline Ta (NC-Ta) was analysed and simulated at various temperatures from 100 K to 1500 K by the molecular dynamics (MD) method. It is shown that with increasing average grain size, the elastic modulus of NC-Ta linearly increases, and the impact factor reaches a value close to 1.8. The critical grain size, as obtained from the Hall-Petch relationship, was found to be about 8.2 nm. For larger grains, the flow stress follows the Hall-Petch relationship, and the thermal behavior of twin bands determines the deformation process. On the other hand, when grains are smaller than the critical size, the relationship between the flow stress and structure transforms into the inverse Hall-Petch relationship, and the deformation mechanism is controlled by grain rotation, boundary sliding or atomic migration. The results of numerical simulations revealed that temperature significantly affects the critical grain size for the plastic deformation of NC-Ta. In addition, it is demonstrated that both the elastic modulus and dislocation density decrease with increasing temperature. These findings provide guidance for the design of polycrystalline tantalum materials with tailored mechanical properties for specific industrial applications such as heat exchangers and condensers in aerospace, bone substitutes in biomedicine, and surface acoustic wave filters or capacitors in electronics.

Analysis of the initial orbital MRI in aquaporin-4 antibody-positive optic neuritis (AQP4-ON): lesion location and lesion length can be predictive of visual prognosis.

PURPOSE: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. METHODS: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years. RESULTS: A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3 mm) than in the recovery group (12.5 ± 5.3 mm) (p = 0.001). CONCLUSION: AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term.