Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.

A Multi-Element Identification System Based on Deep Learning for the Visual Field of Percutaneous Endoscopic Spine Surgery.

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis.

RNA sequencing (RNA-Seq) is widely used to capture transcriptome dynamics across tissues, biological entities, and conditions. Currently, few or no methods can handle multiple biological variables (e.g., tissues/ phenotypes) and their interactions simultaneously, while also achieving dimension reduction (DR). We propose INSIDER, a general and flexible statistical framework based on matrix factorization, which is freely available at https://github.com/kai0511/insider. INSIDER decomposes variation from different biological variables and their interactions into a shared low-rank latent space. Particularly, it introduces the elastic net penalty to induce sparsity while considering the grouping effects of genes. It can achieve DR of high-dimensional data (of > = 3 dimensions), as opposed to conventional methods (e.g., PCA/NMF) which generally only handle 2D data (e.g., sample × expression). Besides, it enables computing 'adjusted' expression profiles for specific biological variables while controlling variation from other variables. INSIDER is computationally efficient and accommodates missing data. INSIDER also performed similarly or outperformed a close competing method, SDA, as shown in simulations and can handle complex missing data in RNA-Seq data. Moreover, unlike SDA, it can be used when the data cannot be structured into a tensor. Lastly, we demonstrate its usefulness via real data analysis, including clustering donors for disease subtyping, revealing neuro-development trajectory using the BrainSpan data, and uncovering biological processes contributing to variables of interest (e.g., disease status and tissue) and their interactions.

Postoperative MRI Findings Following PELD and Their Correlations with Clinical Prognosis are Investigated by Injecting Contrast into Annulus Fibrosus Intraoperatively.

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

Analysis of the success rate of conversion using ibutilide administration in radiofrequency catheter ablation of persistent atrial fibrillation and its effects on postoperative recurrence.

OBJECTIVE: To assess the efficacy of ibutilide administration during radiofrequency catheter ablation of persistent atrial fibrillation (AF), to explore the success rate of conversion and related influential factors, and to analyze the effects of ibutilide on postoperative recurrence. METHODS: A total of 192 patients with persistent AF who underwent catheter ablation from January 1, 2019, to December 31, 2021. These patients failed in conversion of AF to normal sinus rhythm by intraoperative catheter ablation. Patients were categorized into effective group (115 cases) and ineffective group (77 cases) based on whether sinus rhythm was restored after application of ibutilide. RESULTS: The overall success rate of conversion using ibutilide administration was 59.9%. The success rate was associated with weight ((68.12 ± 11.72 vs. 72.83 ± 12.08) kg, P = 0.008), the duration of AF ((34.67 ± 55.68 vs. 66.52 ± 95.21) months, p = 0.008), diameter of left atrium (LAD) ((44.39 ± 5.80 vs. 47.36 ± 6.10) mm,P = 0.002), and N-terminal pro-brain natriuretic peptide (NT-proBNP) level ((854.85 ± 770.84 vs. 662.88 ± 659.18) pg/ml,P = 0.030). The results showed the duration of AF was associated with early recurrence, while early recurrence was not a risk factor for late recurrence. And duration of AF was associated with postoperative maintenance time of normal sinus rhythm, whereas successful conversion into normal sinus rhythm using ibutilide administration had no influence on postoperative maintenance time of normal sinus rhythm. CONCLUSION: Ibutilide showed to be effective in catheter ablation of AF, the success rate of conversion was correlated with the duration of AF, LA diameter, and NT-proBNP level. Besides, the duration of AF was found as a risk factor for early postoperative recurrence, while ibutilide administration for successful conversion had no influence on predicting postoperative recurrence and had no influence on postoperative maintenance time of sinus rhythm.

MSC-Derived Extracellular Vesicles Alleviate NLRP3/GSDMD-Mediated Neuroinflammation in Mouse Model of Sporadic Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, with sporadic form being the predominant type. Neuroinflammation plays a critical role in accelerating pathogenic processes in AD. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) regulate inflammatory responses and show great promise for treating AD. Induced pluripotent stem cell (iPSC)-derived MSCs are similar to MSCs and exhibit low immunogenicity and heterogeneity, making them promising cell sources for clinical applications. This study examined the anti-inflammatory effects of MSC-sEVs in a streptozotocin-induced sporadic mouse model of AD (sAD). The intracisternal administration of iPSC-MSC-sEVs alleviated NLRP3/GSDMD-mediated neuroinflammation, decreased amyloid deposition and neuronal apoptosis, and mitigated cognitive dysfunction. Furthermore, it explored the role of miR-223-3p in the iPSC-MSC-sEVs-mediated anti-inflammatory effects in vitro. miR-223-3p directly targeted NLRP3, whereas inhibiting miR-223-3p almost completely reversed the suppression of NLRP3 by MSC-sEVs, suggesting that miR-223-3p may, at least partially, account for MSC-sEVs-mediated anti-inflammation. Results obtained suggest that intracisternal administration of iPSC-MSC-sEVs can reduce cognitive impairment by inhibiting NLRP3/GSDMD neuroinflammation in a sAD mouse model. Therefore, the present study provides a proof-of-principle for applying iPSC-MSC-sEVs to target neuroinflammation in sAD.

Evaluation of sustainability of mycorrhizal industry development in Fujian Province-based on a combination of CRITIC empowerment method and cloud model.

The sustainable development of mycorrhizal industry is the key to solve the problem of "mycorrhizal forestry contradiction". As a major province of edible mushroom production and forestry resources in China, Fujian Province is also an important origin of mycorrhizal technology research and development, so it is more typical and practical to establish an index system to evaluate the sustainability of mycorrhizal industry development in Fujian Province. Through research interviews and data collection, a sustainable capacity evaluation system of mycorrhizal industry was established with 21 indicators in six dimensions: economic, ecological, social, cultural, political, and technological. A combination of CRITIC empowerment method and cloud model was used to evaluate the sustainability of mycorrhizal industry development in Fujian Province. The results show that although the economic sustainability of the mycorrhizal industry in Fujian Province is average, the overall development trend is good and there are not too many problems. The sustainability of ecological, social and technological levels all have large differences in the development of indicators and the overall development status is average, but overall, the ecological, social and technological levels show a steady forward development from 2017 to 2020. The cultural and political dimensions of sustainability not only have large differences in the development of indicators and an average overall development status, but also have a small development span from 2017 to 2020 and a slow overall development.

Titanium Dioxide (TiO2) Nanoparticle Toxicity in a Caenorhabditis elegans Model.

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO2 NPs) in a Caenorhabditis elegans (C. elegans) model. The effects of commercially available (C-TiO2) and synthetically (S-TiO2) prepared TiO2 NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans. Exposure to TiO2 NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO2 NP concentration increased. The longevity of the nematodes was shortened following TiO2 NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO2 or 10 mg/L S-TiO2. It was therefore concluded that compared with S-TiO2, C-TiO2 possibly causes more toxicity or genotoxicity in the C. elegans model.

A labeled dataset for building HVAC systems operating in faulted and fault-free states.

Open data is fueling innovation across many fields. In the domain of building science, datasets that can be used to inform the development of operational applications - for example new control algorithms and performance analysis methods - are extremely difficult to come by. This article summarizes the development and content of the largest known public dataset of building system operations in faulted and fault free states. It covers the most common HVAC systems and configurations in commercial buildings, across a range of climates, fault types, and fault severities. The time series points that are contained in the dataset include measurements that are commonly encountered in existing buildings as well as some that are less typical. Simulation tools, experimental test facilities, and in-situ field operation were used to generate the data. To inform more data-hungry algorithms, most of the simulated data cover a year of operation for each fault-severity combination. The data set is a significant expansion of that first published by the lead authors in 2020.

Effective Suppression of Amorphous Ga2O and Related Deep Levels on the GaN Surface by High-Temperature Remote Plasma Pretreatments in GaN-Based Metal-Insulator-Semiconductor Electronic Devices.

Gallium nitride (GaN) has been considered one of the most promising materials for the next-generation power and radio-frequency electronic devices, as they can operate at higher voltage, higher frequency, and higher temperature, compared with their silicon (Si) counterparts. However, the fresh GaN surface is susceptible to the natural oxidation composed of Ga2O3, Ga2O, and other intermediate oxidation states. Moreover, the oxidized GaN surface no longer features the distinct atomic step-terrace morphology, resulting in a degraded interface when gate or passivation dielectrics are deposited without appropriate pretreatment. It is responsible for the degraded performance of GaN-based devices such as current collapse and threshold voltage instability. In this study, the proposed high-temperature (500 °C) remote plasma pretreatments (RPPs) can play a significant role in addressing the issue of the deteriorated GaN surface exposed to air. Atomic step-terrace morphology was recovered after 500 °C-RPP due to the removal of oxides and suboxides. First-principles calculations verified that Ga2O at the GaN surface leads to interface states at ∼2.9 eV (EC-E ∼ 0.4 eV) in the bandgap, which is consistent with the increase of interface states at the EC-E range of 0.4-0.9 eV measured through constant-capacitance deep-level transient spectroscopy. Meanwhile, deep interface states and surface-related current collapse are well suppressed in GaN metal-insulator-semiconductor devices. These improved properties by 500 °C-RPP are generalizable to a broader range, including pre-gate and pre-passivation treatment, of which a decent surface/interface is desirable for high-performance GaN-based devices.

Effects of single session transcranial direct current stimulation on aerobic performance and one arm pull-down explosive force of professional rock climbers.

Objective: To explore the effects of single-session transcranial direct current stimulation (tDCS) on aerobic performance and explosive force in the one-arm pull-down of long-term trained rock climbers. Method: Twenty athletes (twelve male and eight female) from the Rock Climbing Team of Hunan province (Hunan, China) were selected for a randomized double-blind crossover study. After baseline tests, All subjects visited laboratories twice to randomly receive either sham or a-tDCS at a current intensity of 2 mA for 20 min. The two visits were more than 72 h apart. Immediately after each stimulation, subjects completed a 9-min 3-level-load aerobic test and a one-arm pull-down test. Results: Differences in the heart rate immediately after 9-min incremental aerobic exercises revealed no statistical significance between each group (p > 0.05). However, the decrease in heart rate per unit time after exercise after real stimulation was significantly better than before stimulation (p < 0.05), and no statistical significance was observed between after sham stimulation and before stimulation (p > 0.05). One-arm pull-down explosive force on both sides after real stimulation was improved by a-tDCS compared with before stimulation, but with no significant difference (p > 0.05). Real stimulation was significantly improved, compared with sham stimulation on the right side (p < 0.05). Conclusion: Single-session tDCS could potentially benefit sports performance in professional athletes.

CCL3 in the bone marrow microenvironment causes bone loss and bone marrow adiposity in aged mice.

The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs' differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs' osteogenic differentiation potential by blocking ß-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research.

Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.

A retrospective study of the mid-term efficacy of full-endoscopic annulus fibrosus suture following lumbar discectomy.

Aims: Full-endoscopic discectomy is associated with a high risk of disc reherniation due to the poor mechanical strength of the annulus fibrosus after scar healing. It is technically difficult to place a full-endoscopic annulus fibrosus suture. We designed an annulus fibrosus suture device that can be used to suture annulus defects under microendoscopy. The present study investigated the safety and feasibility of this technology. Patients and Methods: We retrospectively analyzed the outcomes of patients who underwent surgical treatment for lumbar disc herniation (LDH) from January 2018 to October 2020. We compared 40 patients with LDH treated with full-endoscopic annulus fibrosus suture following lumbar discectomy (LD + AFS group) with 42 patients treated with lumbar discectomy alone (LD group) regarding demographic data, symptoms, and recurrence and reoperation rates. Lumbar MRI and CT were performed 3 and 12 months. A 10-point visual analog scale (VAS) and the Oswestry Disability Index (ODI) was used to evaluate pain and the lumbar spine function. Results: The cohort comprised 82 patients, including 40 patients in the LD + AFS group and 42 in the LD group. All operations were successfully completed without serious complications. Reherniation occurred in no patients in the LD + AFS group and three patients in the LD group. The VAS scores for lumbar and leg pain and ODI score were significantly improved postoperatively (p < 0.05). Conclusion: Compared with conventional lumbar discectomy, full-endoscopic annulus fibrosus suture following full-endoscopic lumbar discectomy is a safe and effective minimally invasive technique that reduces the LDH recurrence rate.

Percutaneous endoscopic lumbar discectomy via the medial foraminal and interlaminar approaches: A comparative study with 2-year follow-up.

Objective: The purpose of this study was to analyze the clinical effect of percutaneous endoscopic medial foraminal discectomy (PEMFD) in the treatment of lumbar disc herniation (LDH). Methods: We retrospectively examined and compared clinical data from 39 single-level LDH patients who underwent PEID and 47 who underwent PEMFD. All the patients were diagnosed with single-level LDH and were treated in Xuzhou Central Hospital for single-segmental lumbar disc herniation between June 2017 and December 2019. Collect and count surgical-related indicators, intraoperative bleeding volume and 24-hour postoperative drainage volume, lower extremity numbness Visual Analogue Scale (VAS), the pain VAS and lumbar Oswestry Disability Index (ODI) scores. Results: Intraoperative bleeding volume and 24-hour postoperative drainage volume were significantly lower in the PEMFD group (p < 0.05). Operation time and length of hospital stay did not significantly differ between the groups. Transient spinal cord injury and surgical site infection did not occur. Recurrence occurred in two patients in each group. Repeat surgery in these patients demonstrated remarkable epidural scarring in the PEID group patients; no scarring was evident in the PEMFD group patients. The numbness VAS score 72 h after surgery and the pain VAS and ODI scores 1 month after surgery significantly differed between groups; however, pain VAS and ODI scores 6, 12, and 24 months after surgery did not. At last follow-up, the modified MacNab criteria outcome did not significantly differ between the groups. Conclusion: PEMFD and PEID have similar short- and medium-term outcomes. However, PEMFD has several advantages: simplicity, lower bleeding volume, and preservation of the LF.

Chinese physical fitness standard for campus football players: A pilot study of 765 children aged 9 to 11.

Objectives: In 2022, 55 million Chinese children participate in campus football; however, there is no physical fitness standard, making it a priority task to enhance the current national program. This study aimed to explore a pilot method for the development of a reliable physical fitness standard. Methods: This study examined 765 male football players aged 9 to 11 in 2020 and 2022. The anthropometric and physical fitness assessments were conducted in accordance with the Chinese Football Association's field manuel. Physical fitness tests include sit and reach test, t test, 30 m run test, and vertical jump test. Physical fitness standard was modeled using the generalized additive models for location, scale, and shape (GAMLSS). Data were fitted with appropriate GAMLSS distributions and smoothing term. P-splines were applied to smooth the model's parameters using the default local maximum likelihood method and link functions. Following diagnostics of fitted models, age-specific centile estimations were computed for physical fitness tests. In addition, players in each age group were categorized according to their body mass index as normal weight or overweight/obese. Welch's t-test was utilized to compare the group differences in physical fitness testing. The significance level was chosen at p < 0.05. Results: Sit and reach test, t test, 30 m run test, and vertical jump test data were fitted with original Sinh-Arcsinh, Box-Cox power exponential, Box-Cox power exponential, and Box-Cox Cole and Green, respectively. Physical fitness standard for each age group is presented as tabulated centiles (1p, 3p, 5p, 15p, 25p, 50p, 75p, 85p, 95p, 97p, 99p). Overweight/obese campus football players did significantly worse (p < 0.05) on the t test, 30 m run test, and vertical jump test than their normal-weight peers of the same age. Conclusion: This study developed the first physical fitness standard for 9 to 11-year-old campus football players in China. We made three recommendations to Chinese policymakers on sample size, data management, and field procedure for the creation of a national physical fitness standard.

The IFN-γ-related long non-coding RNA signature predicts prognosis and indicates immune microenvironment infiltration in uterine corpus endometrial carcinoma.

Background: One of the most common diseases that have a negative impact on women's health is endometrial carcinoma (EC). Advanced endometrial cancer has a dismal prognosis and lacks solid prognostic indicators. IFN-γ is a key cytokine in the inflammatory response, and it has also been suggested that it has a role in the tumor microenvironment. The significance of IFN-γ-related genes and long non-coding RNAs in endometrial cancer, however, is unknown. Methods: The Cancer Genome Atlas (TCGA) database was used to download RNA-seq data from endometrial cancer tissues and normal controls. Genes associated with IFN-γ were retrieved from the gene set enrichment analysis (GSEA) website. Co-expression analysis was performed to find lncRNAs linked to IFN-γ gene. The researchers employed weighted co-expression network analysis (WGCNA) to find lncRNAs that were strongly linked to survival. The prognostic signature was created using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The training cohort, validation cohort, and entire cohort of endometrial cancer patients were then split into high-risk and low-risk categories. To investigate variations across different risk groups, we used survival analysis, enrichment analysis, and immune microenvironment analysis. The platform for analysis is R software (version X64 3.6.1). Results: Based on the transcript expression of IFN-γ-related lncRNAs, two distinct subgroups of EC from TCGA cohort were formed, each with different outcomes. Ten IFN-γ-related lncRNAs were used to build a predictive signature using Cox regression analysis and the LASSO regression, including CFAP58, LINC02014, UNQ6494, AC006369.1, NRAV, BMPR1B-DT, AC068134.2, AP002840.2, GS1-594A7.3, and OLMALINC. The high-risk group had a considerably worse outcome (p < 0.05). In the immunological microenvironment, there were also substantial disparities across different risk categories. Conclusion: Our findings give a reference for endometrial cancer prognostic type and immunological status assessment, as well as prospective molecular markers for the disease.

Identification of TARDBP Gly298Ser as a founder mutation for amyotrophic lateral sclerosis in Southern China.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by predominant impairment of upper and lower motor neurons. Over 50 TARDBP mutations have been reported in both familial (FALS) and sporadic ALS (SALS). Some mutations in TARDBP, e.g. A382T and G294V, have genetic founder effects in certain geographic regions. However, such prevalence and founder effect have not been reported in Chinese. METHODS: Whole-exome sequencing (WES) was performed in 16 Chinese FALS patients, followed by Sanger sequencing for the TARDBP p.Gly298Ser mutation (G298S) in 798 SALS patients and 1,325 controls. Haplotype analysis using microsatellites flanking TARDBP was conducted in the G298S-carrying patients and noncarriers. The geographic distribution and phenotypic correlation of the TARDBP mutations reported worldwide were reviewed. RESULTS: WES detected the TARDBP G298S mutation in 8 FALS patients, and Sanger sequencing found additional 8 SALS cases, but no controls, carrying this mutation. All the 16 cases came from Southern China, and 7 of these patients shared the 117-286-257-145-246-270 allele for the D1S2736-D1S1151-D1S2667-D1S489-D1S434-D1S2697 markers, which was not found in the 92 non-carrier patients (0/92) (p < 0.0001) and 65 age-matched and neurologically normal individuals (0/65) (p < 0.0001). The A382T and G298S mutations were prevalent in Europeans and Eastern Asians, respectively. Additionally, carriers for the M337V mutation are dominated by bulbar onset with a long survival, whereas those for G298S are dominated by limb onset with a short survival. CONCLUSIONS: Some prevalent TARDBP mutations are distributed in a geographic pattern and related to clinical profiles. TARDBP G298S mutation is a founder mutation in the Southern Chinese ALS population.

Fertility Does Not Alter Disease Progression in ALS Patients of Childbearing Age: A Three Centers Retrospective Analysis in Southern China.

Background: Limited data exists on the clinical features of patients with amyotrophic lateral sclerosis (ALS) during reproductive ages. Objective: Our study characterized the clinical features of ALS and the effects of pregnancy on disease progression in patients with ALS. Methods: We performed a retrospective study of female patients with ALS in three ALS research centers in southern China from 2009 to 2021. Data regarding fertility status, and clinical and genetic features, were collected. Age-matched male patients with ALS served as controls. The patients were divided into the following two subgroups: patients with symptom onset within 1 year of pregnancy and patients with symptom onset over 1 year group after pregnancy. Results: A total of 52 female and 52 matched male patients were enrolled. There were no differences in female and male patients in the mean age of symptom onset, the mean baseline ALSFRS-R score, or median reduction of ALSFRS-R score (p > 0.05). The mean age of first pregnancy was 25.57 ± 4.40) years. The mean age of first pregnancy in the over 1 year group was lower than that in the within 1 year group (p= 0.01). There was no difference in the median reduction of ALSFRS-R between the two subgroups. In the univariate analysis, diagnostic delay was highly correlated with the disease progression, with short delay representing rapid progress. No multicollinearity was found among every variable. In addition, 40.38% patients carried ALS-related gene variants. The proportion with gene mutations in the within 1 year group was higher than that in the over 1 year group (p < 0.01). Furthermore, SETX was the most frequently mutated gene in this cohort (16.67%) including 4 uncertain mutation. Conclusion: Pregnancy and fertility were not associated with disease progression. Diagnostic delay was correlated with disease progression in this cohort. In addition, SETX might be a gene of concern for ALS patients of childbearing age.