CT-based radiomics models predict spontaneous intracerebral hemorrhage expansion and are comparable with CT angiography spot sign.

Background and purpose: This study aimed to investigate the efficacy of radiomics, based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) images, in predicting early hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (SICH). Additionally, the predictive performance of these models was compared with that of the established CTA spot sign. Materials and methods: A retrospective analysis was conducted using CT images from 182 patients with SICH. Data from the patients were divided into a training set (145 cases) and a testing set (37 cases) using random stratified sampling. Two radiomics models were constructed by combining quantitative features extracted from NCCT images (the NCCT model) and CTA images (the CTA model) using a logistic regression (LR) classifier. Additionally, a univariate LR model based on the CTA spot sign (the spot sign model) was established. The predictive performance of the two radiomics models and the spot sign model was compared according to the area under the receiver operating characteristic (ROC) curve (AUC). Results: For the training set, the AUCs of the NCCT, CTA, and spot sign models were 0.938, 0.904, and 0.726, respectively. Both the NCCT and CTA models demonstrated superior predictive performance compared to the spot sign model (all P < 0.001), with the performance of the two radiomics models being comparable (P = 0.068). For the testing set, the AUCs of the NCCT, CTA, and spot sign models were 0.925, 0.873, and 0.720, respectively, with only the NCCT model exhibiting significantly greater predictive value than the spot sign model (P = 0.041). Conclusion: Radiomics models based on NCCT and CTA images effectively predicted HE in patients with SICH. The predictive performances of the NCCT and CTA models were similar, with the NCCT model outperforming the spot sign model. These findings suggest that this approach has the potential to reduce the need for CTA examinations, thereby reducing radiation exposure and the use of contrast agents in future practice for the purpose of predicting hematoma expansion.

Baicalein inhibits apoptosis and autophagy induced by chlorpyrifos exposure to kidney of Cyprinus carpio through activation of PI3K/AKT pathway.

Chlorpyrifos (CPF), a widely used organophosphate pesticide that has caused large-scale contamination globally, has become a major concern. Baicalein (BAI), as a flavonoid extract, shows anti-inflammatory as well as antioxidant activities. The kidneys of fish serve to excrete toxins and are major target organs for environmental contaminants. However, it is not obvious whether BAI can counteract the damage caused by CPF exposure to fish kidneys. Therefore, we conducted a 30-day simulation of CPF poisoning and/or BAI treatment by adding 23.2 µg/L CPF to water and/or 0.15 g/kg BAI to feed. In the transmission electron microscopy results, we observed obvious phenomenon of autophagy and apoptosis in the CPF group, and the TUNEL staining and immunofluorescence of LC3B and p62 double-staining results confirmed that CPF induced autophagy and apoptosis in the kidney of common carp. Furthermore, CPF induced the increase of ROS level and inhibition of PI3K and Nrf2 pathways, which in turn triggered oxidative stress, autophagy and apoptosis in carp kidney according to western blot, RT-qPCR and kit assays. However, addition of BAI significantly alleviated oxidative stress, autophagy and apoptosis due to binding to PI3K protein. Additionally, through phylogenetic tree and structural domain analyses, we also found that the binding sites of BAI and PI3K are conserved in a variety of representative species. These results suggest that BAI antagonizes CPF-caused renal impairments in carp involving the PI3K/AKT pathway and the Nrf2 pathway. Our findings provide new insights into the nephrotoxicity effects of CPF and the potential use of BAI as a detoxification agent for CPF intoxication.

Fine mapping of the major gene BhHLS1 controlling seed size in wax gourd (Benincasa hispida).

Introduction/Background: The seed size of wax gourds is an important agronomic trait; however, the associated genes have not yet been reported. Methods: In this study, we used a high-density genetic map constructed based on F8 recombinant inbred line populations derived from a cross between MY-1 (large seed) and GX-71 (small seed) strains to detect quantitative trait locis (QTLs) for seed-size-related traits in wax gourd over a two-year period. Results: Two stable QTLs (qSL10 and qSW10) for seed length (SL) and seed width (SW) on chromosome 10 were repeatedly detected over two years (2021-2022). qSL10 had a phenotypic variation rate of 75.30% and 80.80% in 2021 and 2022, respectively. Whereas, qSW10 had a phenotypic variation rate of 66.60% and 73.80% in 2021 and 2022, respectively. Further, a single nucleotide polymorphism mutation was found to cause early termination of Bch10G006400 (BhHLS1) translation in GX-71 through sequencing analysis of candidate genes. Based on gene functional annotation and quantitative real-time PCR analyses, BhHLS1 encoded a probable N-acetyltransferase HLS1-like protein and its expression level was significantly different between parents. Therefore, BhHLS1 is a major candidate gene associated with a one-factor polymorphism regulating the SL and SW of wax gourds. Finally, based on variation in the BhHLS1 sequence, a cleaved amplified polymorphic sequence marker was developed for the molecular marker-assisted breeding of wax gourds. Discussion: Overall, this study is of great significance for the genetic improvement of seed size, verification of gene functions, and cultivation of specific germplasm resources for wax gourds.

Genotype-degree of hemolysis correlation in hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). CONCLUSION: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.

Two Putative Pheromone Receptors, but Not Their Cognate Pheromones, Regulate Female Fertility in the Atypical Mating Fungus Colletotrichum fructicola.

Colletotrichum fungi are a group of damaging phytopathogens with atypical mating type loci (harboring only MAT1-2-1 but not MAT1-1-1) and complex sexual behaviors. Sex pheromones and their cognate G-protein-coupled receptors are conserved regulators of fungal mating. These genes, however, lose function frequently among Colletotrichum species, indicating a possibility that pheromone signaling is dispensable for Colletotrichum sexual reproduction. We have identified two putative pheromone-receptor pairs (PPG1:PRE2, PPG2:PRE1) in C. fructicola, a species that exhibits plus-to-minus mating type switching and plus-minus-mediated mating line development. Here, we report the generation and characterization of gene-deletion mutants for all four genes in both plus and minus strain backgrounds. Single-gene deletion of pre1 or pre2 had no effect on sexual development, whereas their double deletion caused self-sterility in both the plus and minus strains. Moreover, double deletion of pre1 and pre2 caused female sterility in plus-minus outcrossing. Double deletion of pre1 and pre2, however, did not inhibit perithecial differentiation or plus-minus-mediated enhancement of perithecial differentiation. Contrary to the results with pre1 and pre2, double deletion of ppg1 and ppg2 had no effect on sexual compatibility, development, or fecundity. We concluded that pre1 and pre2 coordinately regulate C. fructicola mating by recognizing novel signal molecule(s) distinct from canonical Ascomycota pheromones. The contrasting importance between pheromone receptors and their cognate pheromones highlights the complicated nature of sex regulation in Colletotrichum fungi.

Development and validation of early death risk score model for emergency status prediction in very severe aplastic anemia.

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation cohort results were consistent with those of the training cohort. The area under the receiver operating characteristic curve for the model was 0.835 (0.734,0.936) in the training cohort and 0.862 (0.730,0.994) in the validation cohort. The calibration plots showed high agreement, and decision curve analysis showed good benefit in clinical applications. The VSAA Early Death Risk Score Model can help with early identification of emergency VSAA and optimize treatment strategies. Emergency VSAA with high risk is associated with high early death rate, and alternative donor hematopoietic stem cell transplantation could be a better treatment than IST even without HLA-matching.

PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLap53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.

Chaetoglobosin A Contributes to the Antagonistic Action of Chaetomium globosum Strain 61239 Toward the Apple Valsa Canker Pathogen Cytospora mali.

Apple Valsa canker (AVC) weakens apple trees and significantly reduces apple production in China and other East Asian countries. Thus far, very few AVC-targeting biocontrol resources have been described. Here, we present a thorough description of a fungal isolate (Chaetomium globosum, 61239) that has strong antagonistic action toward the AVC causal agent Cytospora mali. Potato dextrose broth culture filtrate of strain 61239 completely suppressed the mycelial growth of C. mali on potato dextrose agar, and strongly constrained the development of AVC lesions in in vitro infection assays. ultra-performance liquid chromatography (UPLC) and HPLC-MS/MS investigations supported the conclusion that strain 61239 produces chaetoglobosin A, an antimicrobial metabolite that inhibits C. mali. Using genome sequencing, we discovered a gene cluster in strain 61239 that may be responsible for chaetoglobosin A production. Two of the cluster's genes-cheA, a PKS-NRPS hybrid enzyme, and cheB, an enoyl reductase-were individually silenced, which significantly decreased chaetoglobosin A accumulation as well as the strain's antagonistic activity against C. mali. Together, the findings of our investigation illustrate the potential use of Chaetomium globosum for the management of AVC disease and emphasize the significant contribution of chaetoglobosin A to the antagonistic action of strain 61239.

Comparison of hematopoietic stem cell transplantation and immunosuppressive therapy as the first-line treatment option for patients with severe hepatitis-associated aplastic anemia.

Hepatitis-associated aplastic anemia (HAAA) is a rare variant of acquired aplastic anemia characterized with a syndrome of bone marrow failure after hepatitis. We retrospectively analyzed the outcomes of consecutive severe HAAA patients who received immunosuppressive therapy (IST, n = 70), matched-sibling donor hematopoietic stem cell transplantation (MSD-HSCT, n = 26) or haploidentical-donor (HID) HSCT (n = 11) as the first-line treatment. In the IST group, the hematologic response (HR) rate was 55.71% at 6 months. In contrast, HSCT recipients exhibited significantly more rapid and sustained hematopoiesis (HR 76.92%, 96.15% and 96.15% at 3, 6 and 12months, respectively). The 5-year overall survival (OS) was not different among IST (83.7 ± 4.9%), MSD-HSCT (93.3 ± 6.4%) and HID-HSCT group (80.8 ± 12.3%). Compared with IST, MSD and HID-HSCT demonstrated a trend of superiority in the estimated 5-year failure-free survival rates (93.3 ± 6.4% vs 64.3 ± 6.0%, p = 0.05; 80.8 ± 12.3% vs 64.3 ± 6.0%, p = 0.57). In subsequent stratified analysis on age, we found that HID-HSCT showed its efficacy and safety among young patients. In sum, MSD-HSCT remains first-line treatment choice for HAAA, whereas HID-HSCT represents an alternative treatment choice in addition to IST for young patients (< 40 years) without a matched sibling donor.

Hetrombopag plus porcine ATG and cyclosporine for the treatment of aplastic anaemia: early outcomes of a prospective pilot study.

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At 6 months, the CR rates were 34.4% in the hetrombopag group and 14.6% in the control group (P = 0.015). The overall response rates at 6 months were 68.7% and 50.0% in the hetrombopag and control groups, respectively. The median time to haematologic response was 56 days and 77 days, and to CR was 96 days and 214 days in the hetrombopag and control groups, respectively. In conclusion, adding hetrombopag to IST as first-line treatment resulted in faster and better haematologic response in SAA.

Antihuman T lymphocyte porcine immunoglobulin combined with cyclosporine as first-line immunosuppressive therapy for severe aplastic anemia in China: a large single-center, 10-year retrospective study.

Background: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009. Objectives: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019. Design: This is a single-center retrospective study of medical records. Methods: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to 2019 at our department. Results: The median age of the patients was 24 (4-75) years, and the median follow-up time was 57.2 months (3 days-137.5 months). There was an early mortality rate of 2.8% with a median death time of 0.9 months (3 days-2.9 months). The overall response rates were 40.6% and 56.1% at 3 and 6 months, respectively. The 5-year cumulative incidences of relapse and clonal evolution were 9.0% [95% confidence interval (CI) = 4.2-16.0%] and 4.5% (95% CI = 1.4-10.6%), respectively. The 5-year overall survival (OS) and event-free survival rates were 83.7% (95% CI = 81.1-86.0%) and 50.4% (95% CI = 47.1-53.5%), respectively. Conclusion: p-ATG combined with CsA for the treatment of AA is effective and safe, and p-ATG can be used as an alternative ATG preparation for the standard IST regimen in areas in which h-ATG is not available.

Long-term outcomes of aplastic anemia with cytogenetic abnormalities at diagnosis.

OBJECTIVES: To elucidate the clinical characteristics of AA patients with cytogenetic abnormalities. METHODS: We retrospectively screened 30 patients (30/1206, 2.5%) with cytogenetic abnormalities from 1206 patients with severe and very severe AA who received immunosuppressive therapy (IST) during the years 2012-2019. RESULTS: The most common abnormalities were trisomy 8 (+8, 10/30, 33.3%) and loss of Y (-Y, 8/30, 26.7%). The abnormal clones disappeared 6 months after IST in 14 patients and sustained in 12 patients. Patients with sustained abnormal clones had a lower hematologic response at 6 months after IST than the disappeared (33.3% vs. 64.3%, p = .116). The hematologic response after IST, 5-year overall survival, 5-year event-free survival, myelodysplastic syndrome or acute myeloid leukemia transformation in AA patients with cytogenetic abnormalities were not statistically different from those in normal cytogenetic patients. CONCLUSION: For AA patients with chromosome abnormalities but ineligible for hematopoietic stem cell transplant, IST is effective and appropriate as first-line treatment.

Iron chelation of hetrombopag in aplastic anemia: a post hoc analysis of a phase II study.

Hetrombopag is the only CFDA-approved thrombopoietin (TPO) receptor agonist for severe aplastic anemia (SAA) in China. Its chemical structure has an iron chelation domain. To explore the iron chelation effect of hetrombopag, we performed a post hoc analysis of the phase II clinical trial (NCT03557099). Thirty-five immunosuppressive therapy (IST)-refractory SAA patients were enrolled in the study, and the longitudinal changes of serum ferritin (SF) were assessed. At 18 weeks post-hetrombopag initiation, 51.4% of patients showed decreased SF levels by a median of 49.0 (18.1-95.5) % from baseline (median ΔSF decrease value, 917.2 ng/ml, range from 104.0 to 7030.0 ng/ml). A decrease in SF was found in 75.0% of hematologic responders and 31.6% of non-responders. Among the 24 patients with iron overload, 12 had decreased SF levels by up to 51% of the baseline. Patients with normal SF levels also showed decreased SF levels, and iron deficiency occurred in two patients. In conclusion, hetrombopag showed a powerful and rapid iron chelation effect.

Development and Application of InDel Markers Linked to Fruit-Shape and Peel-Colour Genes in Wax Gourd.

The wax gourd is commonly grown in many countries because of its high nutritional and economic value. While the genes for the fruit shape and peel colour of wax gourd have been reported, the InDel markers linked to these genes remain undeveloped. In this study, the InDel markers linked to fruit-shape (Bch02G016830) and peel-colour (Bch05G003950) genes were developed from resequenced data. We used 120 inbred lines, 536 isolated populations, and 4 commercial hybrids to evaluate the validity and application value of the InDel markers. The accuracy rates of nine pairs of fruit-shape InDel markers (GX1-GX9) were 84.16-91.66% in 120 inbred lines. The accuracy rates of 27 pairs of peel-colour InDel markers (PS1-PS27) within approximately 3.0 Mb upstream and 3.0 Mb downstream of the peel-colour gene were 100% and those of 6 pairs of peel-colour InDel markers (PS28-PS33) within 3.0-20 Mb upstream and downstream of the peel-colour gene were 55.83-90% in 120 inbred lines. The purity of four commercial hybrids determined using GX1, GX2, PS13, and PS14 was highly consistent with the field results for purity determination. Our results provide important information for genetic linkage map construction, molecular-marker-assisted selective breeding, and purity determination of wax gourd hybrids.

First-line immunosuppressive therapy with rATG and CsA for severe aplastic anemia: 15 years' experience.

Rabbit antithymocyte globulin (rATG) instead of horse ATG has been used for severe aplastic anemia (SAA) patients in China. This study aimed to investigate the hematologic responses and long-term overall survival (OS) outcomes in SAA patients who received rATG and cyclosporine as first-line immunosuppressive therapy. We analyzed data of 542 SAA patients treated with this therapy between 2005 and 2019. The median age was 20 (range, 2-80) years, and the median follow-up time was 45.5 (range, 0.1-191.4) months. The early mortality rate was 3.9%. The overall response rates (ORRs) were 40.2%, 56.1%, and 62.4% at 3, 6, and 12 months, respectively. The 6- and 12-month ORR of patients treated with 3 mg/kg/d of rATG in 2015-2019 seemed higher than that of patients treated with 3.5-3.75 mg/kg/day in 2005-2014 (60.2% vs. 54.9%, P = 0.30 and 69.9% vs. 60.1%, P = 0.049, respectively). The 10-year cumulative incidences of relapse and clonal evolution were 10.6 ± 2.9% and 7.5 ± 1.5%, respectively. The 10-year OS rate and event-free survival rate were 80.1 ± 2.1% and 75.6 ± 3.7%, respectively. Age, disease severity, treatment periods, and the interval from diagnosis to IST were independent predictors of OS. In conclusion, 3 mg/kg/day rATG is effective as first-line treatment for SAA.

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia.

Background: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. Methods: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). Results: There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Conclusion: Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

Enriched Rehabilitation Improves Gait Disorder and Cognitive Function in Parkinson's Disease: A Randomized Clinical Trial.

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson's disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD. Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale-Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI). Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER. Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

Semi-Reliability Probability Damage Assessment of GFRP Bars Embedded in Steam-Curing Concrete Beams Based on the Multiple Factors Related Moisture Absorption Model.

GFRP bars will be damaged due to a series of irreversible hygroscopic chemical reactions under humid and hot curing environmental conditions. The multiple factors related to the moisture absorption model were established through the moisture absorption test of GFRP bars embedded in steam-curing concrete, which considered different curing temperatures, different thicknesses of the protective layer, and different diameters of GFRP bars. Semi-reliability probability damage assessment of GFRP bars embedded in steam-curing concrete was described by introducing the reliability and stochastic theory. Subsequently, the tensile test of GFRP bars was carried out to verify the feasibility of the damage assessment. The results showed that the moisture absorption curves of GFRP bars were basically in line with Fick's law. In addition, the influences of the curing temperature, the thickness of the protective layer, and the diameter on moisture absorption performance were presented. The semi-reliability probability damage assessment model of GFRP bars embedded in steam-curing concrete beams adequately considered the multiple factors related to moisture absorption and the uncertainty and randomness of the influencing factors during the process of moisture absorption.