AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis.

JOURNAL/nrgr/04.03/01300535-202508000-00030/figure1/v/2024-09-30T120553Z/r/image-tiff Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death. However, there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation. Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa. The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function. To do this, we injected retinal degeneration 10 (rd10) mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark- and light-adapted electroretinogram, optical coherence tomography, and immunofluorescence. Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment, and the results from this analysis were verified by real-time polymerase chain reaction and western blotting. AAV2-PDE6B injection significantly upregulated PDE6ß expression, preserved electroretinogram responses, and preserved outer nuclear layer thickness in rd10 mice. Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception, and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice. Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways. Furthermore, the phototransduction-related proteins Pde6α, Rom1, Rho, Aldh1a1, and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment. Finally, Bax/Bcl-2, p-ERK/ERK, and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment. Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Cimifugin Alleviates Chronic Constriction Injury of the Sciatic Nerve by Suppressing Inflammatory Response and Schwann Cell Apoptosis.

Inflammation and Schwann cell apoptosis play critical roles in neuropathic pain after sciatic nerve injury. This study aimed to explore the function and mechanism of cimifugin in lipopolysaccharide (LPS)-stimulated rat Schwann cells and sciatic nerves of rats treated with chronic constriction injury (CCI). Thermal, mechanical and cold hyperalgesia of rats in response to cimifugin or mecobalamin (the positive drug control) treatment were evaluated through behavioral tests. H&E staining of sciatic nerves was performed for pathological observation. ELISA was conducted to assess concentrations of inflammatory cytokines in rat serum and sciatic nerves. The intensity of S100ß in sciatic nerves was determined using immunohistochemistry. Flow cytometry analysis was conducted for detection of Schwann cell apoptosis. RT-qPCR was performed to measure mRNA levels of inflammatory factors in Schwann cells. Immunofluorescence staining was performed to detect cellular p65/NF-κB activity. Western blotting was performed to quantify protein levels of apoptotic markers and factors associated with the NF-κB and MAPK pathways in rat nerves and Schwann cells. As shown by experimental data, cimifugin mitigated thermal, mechanical and cold hyperalgesia of CCI rats. Cimifugin repressed inflammatory cell infiltration, reduced proinflammatory cytokine levels while increasing anti-inflammatory factor (IL-10) level in serum or sciatic nerves of CCI rats. Cimifugin enhanced S100ß expression and downregulated apoptotic markers in vivo. The anti-inflammatory and anti-apoptotic properties of cimifugin were verified in the LPS-stimulated Schwann cells. Moreover, cimifugin suppressed nuclear translocation of p65 NF-κB in vitro and repressed the phosphorylation of IκB, p65 NF-κB, p38 MAPK, ERK1/2, as well as JNK in CCI rats. In conclusion, cimifugin alleviates neuropathic pain after sciatica by suppressing inflammatory response and Schwann cell apoptosis via inactivation of NF-κB and MAPK pathways.

Targeted long-read sequencing identifies missing pathogenic variant in unsolved 11ß-hydroxylase deficiency.

BACKGROUND: 11ß-hydroxylase deficiency (11ß-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11ß-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11ß-OHD. METHODS: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. RESULTS: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269-143,957,579 (hg19) with the insertion of 'ACAG' (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. CONCLUSIONS: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11ß-OHD genetic diagnosis and carrier sequencing.

[Clinical and genetic analysis of two children with TANC2 gene variants and a literature review].

OBJETIVE: To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. METHODS: Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using "TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", "TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). RESULTS: Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c.3398G>A (p.Gly1133Glu) and c.2829+1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+PM2_Supporting+PP3) and the latter was rated as pathogenic (PVS1+PS2+PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17) , intellectual disability (94.1%,16/17) , language and motor retardation (88.2%, 15/17；58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. CONCLUSION: Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.

Gut Microbiome variation in patients with early-stage mild-to-moderate intracerebral hemorrhage: A pilot study exploring therapeutic targets.

BACKGROUND: The significant morbidity and mortality rates of acute intracerebral hemorrhage (ICH) are well-known around the world. The link between gut microbiota and different types of strokes is becoming more studied. The goal of this study was to look at the relationships between intestinal flora and early-stage mild-to-moderate ICH (emICH), and to provide a new perspective for adjunctive treatment of emICH. METHODS: Fecal samples from 100 participants with emICH (n=50) and healthy individuals (n=50) in this study were collected as well as analyzed utilizing 16S rRNA gene amplicon sequencing in order to characterize the gut microbial community. RESULTS: Distinct microbial communities are present within each group, with emICH patients exhibiting a diminished diversity and uniformity in their microbial profiles. A notable shift in the gut microbiota composition of emICH patients has been observed, characterized by an upsurge in pro-inflammatory microbes belonging to the Euryarchaeota phylum and a concurrent decline in beneficial Bacteroidetes species. Concurrently, significant associations and patterns among operational taxonomic units (OTUs) were identified in emICH patients. A panel of biomarkers (WAL_1855D, Methanobrevibacter, Streptococcus, Bacteroides, Coprococcus, Lachnospira) has been effectively utilized to distinguish emICH patients from healthy individuals, with an area under the curve (AUC) of 0.845. Additionally, an analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation uncovered several perturbed pathways in emICH patients, predominantly those related to metabolic processes and the inflammatory response. Moreover, predictive profiling of the microbiome's phenotypic traits suggests that emICH patients are likely to harbor a higher prevalence of Gram-negative bacteria and potential opportunistic pathogens compared to healthy controls. CONCLUSIONS: The gut microbiota ecosystem of emICH patients is disrupted, characterized primarily by an increase in pro-inflammatory microbiota, elevated inflammatory signaling pathways, and metabolic dysregulation. Furthermore, microbiota modulation may be seen as a novel approach for the adjunctive treatment of emICH.

Efficacy and safety of recombinant human thrombopoietin for the treatment of chronic primary immune thrombocytopenia in children and adolescents: A multicentre, randomized, double-blind, placebo-controlled phase III trial.

The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double-blind, placebo-controlled phase III trial was performed. Patients aged 6-17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included. For the trial, part 1 was exploratory and part 2 was the main analysis, with part 1 determining whether part 2 was stratified by age. Patients in part 1 were treated with rhTPO (the 6- to 11-/12- to 17-year-old groups; 1:1). Patients in part 2 were randomized (3:1) to receive either rhTPO treatment or placebo. Patients received rhTPO or placebo at a dose of 300 U/kg once daily for up to 14 days. A total of 68 patients were included [part 1 (12 patients), part 2 (56 patients)]. The total response rate (TRR) in part 1 was 50.0% (95% CI: 21.09%-78.91%). For part 2, the TRR was 58.5% (95% CI: 42.11%-73.68%) and 13.3% (95% CI: 1.66%-40.46%) in the rhTPO and placebo groups (FAS) respectively. The difference in TRR between the rhTPO group and placebo group was 45.2% (95% CI: 22.33%-68.08%) and 44.6% (95% CI: 21.27%-67.85%) on the FAS and per-protocol set (PPS), respectively, which indicates the superiority of rhTPO treatment.

Physiological and Proteomic Analysis of Various Priming on Rice Seed under Chilling Stress.

Rice (Oryza sativa L.) cultivation using direct seeding is susceptible to chilling stress, particularly during seed germination and early seedling growth in the early season of a double cropping system. Alternatively, seed priming with various plant growth-promoting hormones is an effective technique to promote rapid and uniform emergence under chilling stress. Therefore, we evaluated the impact of gibberellin A3 (GA3) and brassinolide (BR) priming on rice seed emergence, examining their proteomic responses under low-temperature conditions. Results indicated that GA3 and BR increased the seed germination rate by 22.67% and 7.33% at 72 h and 35% and 15% at 96 h compared to the control (CK), respectively. Furthermore, proteomic analysis identified 2551, 2614, and 2592 differentially expressed proteins (DEPs) in GA, BR, and CK, respectively. Among them, GA exhibited 84 upregulated and 260 downregulated DEPs, while BR showed 112 upregulated and 102 downregulated DEPs, and CK had 123 upregulated and 81 downregulated DEPs. Notably, under chilling stress, both GA3 and BR are involved in peroxide metabolism, phenylpropanoid biosynthesis, and inositol phosphate metabolism, enhancing antioxidant capacity and providing energy substances for germination. In addition, GA3 triggers the specific regulation of stress responsive protein activation, GTP activation, and ascorbic acid biosynthesis and promotes the stability and integrity of cell membranes, as well as the synthesis of cell walls, providing physical defense for seeds to resist low temperatures. At the same time, BR triggers specific involvement in ribosome synthesis and amino acid synthesis, promoting biosynthetic ability and metabolic regulation to maintain plant life activities under low-temperature stress. Furthermore, the various genes' expression (OsJ_16716, OsPAL1, RINO1) confirmed GA3 and BR involved in peroxide metabolism, phenylpropanoid biosynthesis, and inositol phosphate metabolism, enhancing antioxidant capacity and providing energy substances for germination. This study provides valuable insights into how rice seed embryo responds to and tolerates chilling stress with GA3 seed priming.

Clinical value of macrogenome next-generation sequencing on infections.

Intracranial infection (ICI) is a frequent and serious complication after neurosurgery. Macrogenome next-generation sequencing (mNGS) technology can provide reference for clinical diagnosis and treatment of ICI. This work aimed to explore the application value of mNGS technology in analyzing the clinical characteristics of human immunodeficiency virus (HIV) infection and ICI after neurosurgery. A total of 60 patients with ICI were enrolled as the research objects, all patients underwent routine cerebrospinal fluid analysis and traditional pathogen detection, followed by mNGS genome analysis. Using clinical diagnosis of ICI as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for both detection methods were calculated. Receiver operating characteristic curves were constructed to assess the area under the curve (AUC) for evaluating the clinical value of mNGS in suspected intracranial infectious pathogen diagnosis. Results showed a positivity rate of 71.67% (43 cases) with mNGS compared to 28.33% (17 cases) with traditional pathogen detection methods, demonstrating a significant difference (P < 0.05). The sensitivity of mNGS for detecting ICIs was 83.7%, significantly higher than the 34.88% observed with traditional methods (P < 0.05). The pathogen detection rate of mNGS was higher than traditional methods (P = 0.002), with an AUC of 0.856 (95% CI: 0.638-0.967), significantly greater than the AUC of 0.572 (95% CI: 0.350-0.792) for traditional methods (P < 0.05). mNGS successfully identified microorganisms such as Cryptococcus, Propionibacterium, Staphylococcus, Corynebacterium, Micrococcus, and Candida associated with ICIs. These findings underscore the clinical applicability of mNGS technology in analyzing the characteristics of HIV infection and ICI post-neurosurgical procedures. This technology enables more accurate diagnosis and treatment of ICIs, providing valuable insights for developing effective therapeutic strategies.

Transcriptome analysis reveals the promoting effects of exogenous melatonin on the selenium uptake in grape under selenium stress.

Introduction: Exogenous melatonin (MT) can promote horticultural crops growth under stress conditions. Methods: In this study, the effects of exogenous MT on the accumulation of selenium (Se) in grape were studied under Se stress. Results and discussion: Under Se stress, exogenous MT increased the biomass, content of photosynthetic pigments and antioxidant enzyme activity of grapevines. Compared with Se treatment, MT increased the root biomass, shoot biomass, chlorophyll a content, chlorophyll b content, carotenoids, superoxide dismutase activity, and peroxidase activity by 18.11%, 7.71%, 25.70%, 25.00%, 25.93%, 5.73%, and 9.41%, respectively. Additionally, MT increased the contents of gibberellin, auxin, and MT in grapevines under Se stress, while it decreased the content of abscisic acid. MT increased the contents of total Se, organic Se and inorganic Se in grapevines. Compared with Se treatment, MT increased the contents of total Se in the roots and shoots by 48.82% and 135.66%, respectively. A transcriptome sequencing analysis revealed that MT primarily regulated the cellular, metabolic, and bioregulatory processes of grapevine under Se stress, and the differentially expressed genes (DEGs) were primarily enriched in pathways, such as aminoacyl-tRNA biosynthesis, spliceosome, and flavonoid biosynthesis. These involved nine DEGs and nine metabolic pathways in total. Moreover, a field experiment showed that MT increased the content of Se in grapes and improved their quality. Therefore, MT can alleviate the stress of Se in grapevines and promote their growth and the accumulation of Se.

The electronic and magnetic properties modulated by ferroelectric polarization switching in two-dimensional VSeTe/Sc2CO2 van der Waals heterostructures.

Exploring multiferroic materials that combine magnetic and ferroelectric properties is scientifically interesting and has important technical implications for many functions of nanoscale devices. In this work, spintronics and magnetoelectric coupling devices are proposed in two-dimensional (2D) layered ferromagnetic (FM)/ferroelectric (FE) van de Waals (vdW) heterostructures, VSeTe/Sc2CO2, employing density functional theory (DFT) calculations. The results indicate that the VSeTe/Sc2CO2 vdW heterostructure changes from a metal to a semiconductor in Sc2CO2-P↑ and Sc2CO2-P↓ polarization states. At the same time, the charge at the interface of the VSeTe/Sc2CO2 heterostructure will also be redistributed with the transformation of the ferroelectric polarization state, resulting in the change of the distribution of the electronic states near the Fermi level, and thus the change in the magnetic anisotropy energy (EMAE) of the heterostructure. Interestingly, biaxial strain brings reversibility and non-volatile regulation to the heterostructure of semiconductors and metals. The results provide an effective way to fabricate magnetoelectric coupling devices with 2D multiferroic heterostructures.

Understanding the effect of adsorption sites of CO at cobalt surface on its reactivity with H2/H by DFT calculations.

Cobalt (Co) is widely used in Fischer-Tropsch synthesis (FTS), converting synthesis gas, carbon monoxide + hydrogen (CO + H2), to long-chain hydrocarbons. The adsorption of CO on the Co surface is the key step in FTS. In this work, the effect of CO adsorption sites on the reactions between CO and H2 was investigated by using density functional theory (DFT). The energetics and structures of the reactions between the adsorbed CO (CO*) and H2/adsorbed H2 (H2*)/adsorbed H atom (H*) were calculated. The results show that the reaction between CO* and H2 is initiated by the molecular adsorption of H2 on the Co surface. The reactions between CO* and H2*/H* are influenced by CO adsorption sites. For the reaction system of CO* + H2*, it has the lowest reaction barrier when CO is adsorbed at the hcp site, while for CO* + H*, it has the lowest reaction barrier when CO is adsorbed on the top site. Kinetic analysis indicates that to improve the reactivity of CO + H2 in FTS, the adsorption of CO should be controlled to favour the top and bridge sites. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.

Plasma Metabolomics Indicates Potential Biomarkers and Abnormal Metabolic Pathways in Female Melasma Patients.

BACKGROUND: Melasma is a common and chronic pigmentary disorder with complex pathogenesis, and the relationship between melasma and metabolic syndrome remains elusive. Thus, metabolomics might contribute to the early detection of potential metabolic abnormalities in individuals with melasma. OBJECTIVE: The present study aims to analyze changes in plasma metabolites of female melasma patients and identify disease markers as well as explore potential therapeutic targets. METHODS: Plasma samples from 20 female patients with melasma and 21 healthy female controls that were comparable in terms of age and body mass index were collected for untargeted metabolomics investigations. Ultra-high performance liquid chromatography-mass spectrometry was used to analyze metabolites in the plasma. Metabolic pathway analyses were employed to identify significantly differentially expressed metabolites in melasma patients. Receiver operating characteristic curves were constructed, and correlation analyses were performed using the modified Melasma Area and Severity Index and oxidative stress levels. RESULTS: In contrast to healthy subjects, melasma patients showed significant alterations in 125 plasma metabolites, including amino acids, lipids, and carbohydrate-related metabolites. KEGG pathway analysis suggested that primary pathways associated with the development of melasma include tryptophan metabolism, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. Importantly, based on receiver operating characteristic curves and correlation analyses, several metabolites were identified as robust biomarkers for melasma. CONCLUSION: Collectively, this study identified significant changes in plasma metabolites in melasma patients, providing new insights into the pathogenesis of melasma and opening novel therapeutic avenues.

Association between the C-reactive protein to albumin ratio and poor clinical outcome in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: The C-reactive protein-to-albumin ratio (CAR) is a novel prognostic biomarker of systemic inflammation and nutritional status. The association between CAR and the long-term outcome of spontaneous intracerebral hemorrhage (ICH) remains unclear. METHODS: From January 2014 to September 2016, 497 patients with spontaneous ICH were enrolled in our study from 13 hospitals in Beijing. According to the CAR quartiles, patients were classified into four groups (Q1-Q4). Logistic regression was applied to analyze the relationship between different CAR levels and main outcome (90-day and 1-year mRS 4-6). Restricted cubic splines and receiver operating characteristic (ROC) curves of CAR for poor clinical outcomes were assessed. RESULTS: In the multivariate logistic regression model, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q2, Q3, and Q4 group for 90-day mRS score of 4-6 were 3.64 (1.61-8.23), 3.83 (1.67-8.77), and 8.91 (3.85-20.64). In terms of 1-year mRS score of 4-6, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q3 and Q4 group were 3.31 (1.33-8.22) and 6.87 (2.81-16.78). CONCLUSIONS: A high CAR level was associated with a high risk of long-term adverse prognosis in patients with ICH, and the risk of ICH poor outcome increased steadily with CAR rising in a certain range, and maintained in a high level thereafter.

SnO2-Based Interfacial Engineering towards Improved Perovskite Solar Cells.

Interfacial engineering is of great concern in photovoltaic devices. Metal halide perovskite solar cells (PSCs) have garnered much attention due to their impressive development in power conversion efficiencies (PCEs). Benefiting from high electron mobility and good energy-level alignment with perovskite, aqueous SnO2 as an electron transport layer has been widely used in n-i-p perovskite solar cells. However, the interfacial engineering of an aqueous SnO2 layer on PSCs is still an obscure and confusing process. Herein, we proposed the preparation of n-i-p perovskite solar cells with different concentrations of SnO2 as electron transport layers and achieved optimized PCE with an efficiency of 20.27%. I Interfacial engineering with regard to the SnO2 layer is investigated by observing the surface morphology, space charge-limited current (SCLC) with the use of an electron-only device, and time-resolved photoluminescence (TRPL) of perovskite films.

A Study of Classroom Behavior Recognition Incorporating Super-Resolution and Target Detection.

With the development of educational technology, machine learning and deep learning provide technical support for traditional classroom observation assessment. However, in real classroom scenarios, the technique faces challenges such as lack of clarity of raw images, complexity of datasets, multi-target detection errors, and complexity of character interactions. Based on the above problems, a student classroom behavior recognition network incorporating super-resolution and target detection is proposed. To cope with the problem of unclear original images in the classroom scenario, SRGAN (Super Resolution Generative Adversarial Network for Images) is used to improve the image resolution and thus the recognition accuracy. To address the dataset complexity and multi-targeting problems, feature extraction is optimized, and multi-scale feature recognition is enhanced by introducing AKConv and LASK attention mechanisms into the Backbone module of the YOLOv8s algorithm. To improve the character interaction complexity problem, the CBAM attention mechanism is integrated to enhance the recognition of important feature channels and spatial regions. Experiments show that it can detect six behaviors of students-raising their hands, reading, writing, playing on their cell phones, looking down, and leaning on the table-in high-definition images. And the accuracy and robustness of this network is verified. Compared with small-object detection algorithms such as Faster R-CNN, YOLOv5, and YOLOv8s, this network demonstrates good detection performance on low-resolution small objects, complex datasets with numerous targets, occlusion, and overlapping students.

Development and validation of a nomogram for predicting intellectual disability in children with cerebral palsy.

Objective: Intellectual disability (ID) is a prevalent comorbidity in children with cerebral palsy (CP), presenting significant challenges to individuals, families and society. This study aims to develop a predictive model to assess the risk of ID in children with CP. Methods: We analyzed data from 885 children diagnosed with CP, among whom 377 had ID. Using least absolute shrinkage and selection operator regression, along with univariate and multivariate logistic regression, we identified key predictors for ID. Model performance was evaluated through receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Bootstrapping validation was also employed. Results: The predictive nomogram included variables such as preterm birth, CP subtypes, Gross Motor Function Classification System level, MRI classification category, epilepsy status and hearing loss. The model demonstrated strong discrimination with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% CI: 0.7504-0.8116) and a bootstrapped AUC of 0.7624 (95% CI: 0.7216-0.8032). Calibration plots and the Hosmer-Lemeshow test indicated a good fit (χ2= 7.9061, p = 0.4427). DCA confirmed the model's clinical utility. The cases were randomly divided into test group and validation group at a 7:3 ratio, demonstrating strong discrimination, good fit and clinical utility; similar results were found when stratified by sex. Conclusions: This predictive model effectively identifies children with CP at a high risk for ID, facilitating early intervention strategies. Stratified risk categories provide precise guidance for clinical management, aiming to optimize outcomes for children with CP by leveraging neuroplasticity during early childhood.

Development and Validation of a Two-step Model to Predict Outcomes After Endovascular Treatment for Patients With Acute Ischemic Stroke.

BACKGROUND: Physicians and patients are eager to know likely functional outcomes at different stages of treatment after acute ischemic stroke (AIS). The aim of this study was to develop and validate a 2-step model to assess prognosis at different time points (pre- and posttreatment) in patients with AIS having endovascular thrombectomy (EVT). METHODS: The prediction model was developed using a prospective nationwide Chinese registry (ANGEL-ACT). A total of 1676 patients with AIS who underwent EVT were enrolled into the study and randomly divided into development (n=1351, 80%) and validation (n=325, 20%) cohorts. Multivariate logistic regression, least absolute shrinkage and selection operator regression, and the random forest recursive feature elimination algorithm were used to select predictors of 90-day functional independence. We constructed the model via discrimination, calibration, decision curve analysis, and feature importance. RESULTS: The incidence of 90-day functional independence was 46.3% and 40.6% in the development and validation cohorts, respectively. The area under the curve (AUC) for model 1 which included 5 pretreatment predictors (age, admission National Institutes for Health Stroke Scale score, admission glucose level, admission systolic blood pressure, and Alberta Stroke Program Early Computed Tomography score) was 0.699 (95% confidence interval [CI], 0.668-0.730) in the development cohort and 0.658 (95% CI, 0.592-0.723) in the validation cohort. Two treatment-related predictors (time from stroke onset to puncture and successful reperfusion) were added to model 2 which had an AUC of 0.719 (95% CI, 0.688-0.749) and 0.650 (95% CI, 0.585-0.716) in the development cohort and validation cohorts, respectively. CONCLUSIONS: The 2-step prediction model could be useful for predicting the functional independence in patients with AIS 90-days after EVT.

Combined climate change and dispersal capacity positively affect Hoplobatrachus chinensis occupancy of agricultural wetlands.

Global warming significantly impacts amphibian populations globally, and modeling helps understand these effects. Here, we used MaxEnt and MigClim models to predict the impact of climate change on habitat suitability for Hoplobatrachus chinensis. Our results indicate that temperature is a key factor affecting H. chinensis distribution. Increasing temperatures positively correlated with habitat suitability, with suitable habitat expanding northward by 2060 while maintaining suitability in the southern parts of the range. We found a 25.18% overlap between the current potential suitable habitat of H. chinensis and agricultural wetlands. Our model indicated that H. chinensis might be able to track shifts in suitable habitats under climate change given a 15 km dispersal ability per generation. Climate change will likely expand suitable habitat for H. chinensis. Our predictions offer important guidance for the conservation of the species, especially for the integrated role of natural and agricultural wetlands such as rice paddies.

Multi-omics analysis reveals the effects of host-rumen microbiota interactions on growth performance in a goat model.

The growth rate of young ruminants has been associated with production performance in later life, with recent studies highlighting the importance of rumen microbes in supporting the health and growth of ruminants. However, the specific role of rumen epithelium bacteria and microbiota-host interactions in influencing the early life growth rate of ruminants remains poorly understood. In this study, we investigated the rumen fermentation pattern, microbiota characteristics, and global gene expression profiles of the rumen epithelium in 6-month-old goats with varying growth rates. Our results showed that goats with high average daily gain (HADG) exhibited higher rumen propionate concentrations. Goats with low average daily gain (LADG) had the higher relative abundances of rumen epithelium bacteria genera U29-B03 and Quinella, while exhibiting a lower relative abundance of Lachnospiraceae UCG-009. In the rumen fluid, the relative abundances of bacteria genus Alloprevotella were lower and Desulfovibrio were higher in LADG goats compared to HADG goats. Additionally, the relative abundance of fungal genus Symmetrospora was lower in LADG goats compared to HADG goats. Transcriptome analysis showed that 415 genes were differentially expressed between LADG and HADG goats, which were enriched in functions related to cell junction and cell adhesion, etc. Correlation analysis revealed that rumen epithelium bacteria genera UCG-005 and Candidatus Saccharimonas were negatively associated, while Lachnospiraceae NK3A20 group and Oscillospiraceae NK4A214 group were positively associated with average daily gain (ADG) and genes related to barrier function. The rumen fluid bacteria genus Alloprevotella was positively correlated, while Desulfovibrio was negatively correlated with rumen propionate and ammoniacal nitrogen (NH3-N) concentrations, as well as genes related to barrier function and short chain fatty acids (SCFAs) transport. In summary, our study reveals that the higher ruminal fermentation efficiency, improved rumen epithelial barrier functions, and enhanced SCFAs transport in HADG goats could be attributed to the rumen microbiota, particularly the rumen epithelium bacteria, such as Lachnospiraceae and Oscillospiraceae NK4A214 group.