Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer.

Endometrial cancer (EC) is a malignancy that poses a threat to woman's health worldwide. Building upon prior work, we explored the inhibitory effect of verteporfin on EC. We showed that verteporfin can damage the mitochondria of EC cells, leading to a decrease of mitochondrial membrane potential and an increase in ROS (reactive oxygen species). In addition, verteporfin treatment was shown to inhibit the proliferation and migration of EC cells, promote apoptosis, and reduce the expression of mitophagy-related proteins PINK1/parkin and TOM20. The ROS inhibitor N-Acetyl Cysteine was able to rescue the expression of PINK1/parkin proteins. This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.

Genetic variation in IL-4 activated tissue resident macrophages alters the epigenetic state to determine strain specific synergistic responses to LPS.

How macrophages in the tissue environment integrate multiple stimuli will depend on the genetic background of the host, but this is poorly understood. Here, we investigated C57BL/6 and BALB/c strain specific in vivo IL-4 activation of tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with a greater association of induced genes with super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling revealed BL/6 specific enrichment of NF-κB, IRF, and STAT motifs. Additionally, IL-4-activated BL/6 TRMs demonstrated an augmented synergistic response upon in vitro lipopolysaccharide (LPS) exposure compared to BALB/c TRMs, despite naïve BALB/c TRMs displaying a more robust transcriptional response to LPS than naïve BL/6 TRMs. Single-cell RNA sequencing (scRNA-seq) analysis of mixed bone marrow chimeric mice indicated that transcriptional differences between BL/6 and BALB/c TRMs, and synergy between IL-4 and LPS, are cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming resulting in strain specific synergistic responses to LPS exposure.

Utilizing ChatGPT as a scientific reasoning engine to differentiate conflicting evidence and summarize challenges in controversial clinical questions.

OBJECTIVE: Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPT as a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research. MATERIALS AND METHODS: We evaluated ChatGPT's effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity. RESULTS: The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT's conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings. DISCUSSION: Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT's inherent logical reasoning capabilities. CONCLUSION: This study demonstrated ChatGPT's capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT's outputs are inferences drawn from the input literature and could be harmful to clinical practice.

Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53.

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown. Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53 binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this self-repression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25 as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53 from binding to W-box elements on the AtWRKY53 promoter and thus counteracted the self-repression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid (SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and NahG transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence, which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

Eye-Readable and Wearable Colorimetric Sensor Arrays for In Situ Monitoring of Volatile Organic Compounds.

Wearable sensors utilize changes in color as a response to physiological stimuli, making them easily recognizable by the naked eye. These colorimetric wearable sensors offer benefits such as easy readability, rapid responsiveness, cost-effectiveness, and straightforward manufacturing techniques. However, their applications in detecting volatile organic compounds (VOCs) in situ have been limited due to the low concentration of complex VOCs and complicated external interferences. Aiming to address these challenges, we introduced readable and wearable colorimetric sensing arrays with a microchannel structure and highly gas-sensitive materials for in situ detection of complex VOCs. The highly gas-sensitive materials were designed by loading gas-sensitive dyes into the porous metal-organic frameworks and further depositing the composites on the electrospun nanofiber membrane. The colorimetric sensor arrays were fabricated using various gas-sensitive composites, including eight dye/MOF composites that respond to various VOCs and two Pd2+/dye/MOF composites that respond to ethylene. This enables the specific recognition of multiple characteristic VOCs. A microfluidic channel made of polydimethylsiloxane (PDMS) was integrated with different colorimetric elements to create a wearable sensor array. It was attached to the surface of fruits to collect and monitor VOCs using the DenseNet classification method. As a proof of concept, we demonstrated the feasibility of the wearable sensing system in monitoring the ripening process of fruits by continuously measuring the VOC emissions from the skin of the fruit.

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, ß-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, ß-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Neural Q-learning for discrete-time nonlinear zero-sum games with adjustable convergence rate.

In this paper, an adjustable Q-learning scheme is developed to solve the discrete-time nonlinear zero-sum game problem, which can accelerate the convergence rate of the iterative Q-function sequence. First, the monotonicity and convergence of the iterative Q-function sequence are analyzed under some conditions. Moreover, by employing neural networks, the model-free tracking control problem can be overcome for zero-sum games. Second, two practical algorithms are designed to guarantee the convergence with accelerated learning. In one algorithm, an adjustable acceleration phase is added to the iteration process of Q-learning, which can be adaptively terminated with convergence guarantee. In another algorithm, a novel acceleration function is developed, which can adjust the relaxation factor to ensure the convergence. Finally, through a simulation example with the practical physical background, the fantastic performance of the developed algorithm is demonstrated with neural networks.

Explore the effect of apparent temperature and air pollutants on the admission rate of acute myocardial infarction in Chongqing, China: a time-series study.

OBJECTIVE: Limited research has been conducted on the correlation between apparent temperature and acute myocardial infarction (AMI), as well as the potential impact of air pollutants in modifying this relationship. The objective of this study is to investigate the lagged effect of apparent temperature on AMI and assess the effect modification of environmental pollutants on this association. DESIGN: A time-series study. SETTING AND PARTICIPANTS: The data for this study were obtained from the Academy of Medical Data Science at Chongqing Medical University, covering daily hospitalisations for AMI between 1 January 2015 and 31 December 2016. Meteorological and air pollutant data were provided by China's National Meteorological Information Centre. OUTCOME MEASURES: We used a combined approach of quasi-Poisson generalised linear model and distributed lag non-linear model to thoroughly analyse the relationships. Additionally, we employed a generalised additive model to investigate the interaction between air pollutants and apparent temperature on the effect of AMI. RESULT: A total of 872 patients admitted to hospital with AMI were studied based on the median apparent temperature (20.43°C) in Chongqing. Low apparent temperature (10th, 7.19℃) has obvious lagged effect on acute myocardial infarction, first appearing on the 8th day (risk ratio (RR) 1.081, 95% CI 1.010 to 1.158) and the greatest risk on the 11th day (RR 1.094, 95% CI 1.037 to 1.153). No lagged effect was observed at high apparent temperature. In subgroup analysis, women and individuals aged 75 and above were at high risk. The interaction analysis indicates that there exist significant interactions between PM2.5 and high apparent temperature, as well as nitrogen dioxide (NO2) and low apparent temperature. CONCLUSION: The occurrence of decreased apparent temperature levels was discovered to be linked with a heightened relative risk of hospitalisations for AMI. PM2.5 and NO2 have an effect modification on the association between apparent temperature and admission rate of AMI.

Extrusion Printing of Surface-Functionalized Metal-Organic Framework Inks for a High-Performance Wearable Volatile Organic Compound Sensor.

Wearable sensors hold immense potential for real-time and non-destructive sensing of volatile organic compounds (VOCs), requiring both efficient sensing performance and robust mechanical properties. However, conventional colorimetric sensor arrays, acting as artificial olfactory systems for highly selective VOC profiling, often fail to meet these requirements simultaneously. Here, a high-performance wearable sensor array for VOC visual detection is proposed by extrusion printing of hybrid inks containing surface-functionalized sensing materials. Surface-modified hydrophobic polydimethylsiloxane (PDMS) improves the humidity resistance and VOC sensitivity of PDMS-coated dye/metal-organic frameworks (MOFs) composites. It also enhances their dispersion within liquid PDMS matrix, thereby promoting the hybrid liquid as high-quality extrusion-printing inks. The inks enable direct and precise printing on diverse substrates, forming a uniform and high particle-loading (70 wt%) film. The printed film on a flexible PDMS substrate demonstrates satisfactory flexibility and stretchability while retaining excellent sensing performance from dye/MOFs@PDMS particles. Further, the printed sensor array exhibits enhanced sensitivity to sub-ppm VOC levels, remarkable resistance to high relative humidity (RH) of 90%, and the differentiation ability for eight distinct VOCs. Finally, the wearable sensor proves practical by in situ monitoring of wheat scab-related VOC biomarkers. This study presents a versatile strategy for designing effective wearable gas sensors with widespread applications.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-ß1/Smads signaling pathway.

BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.

Human-induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno-free and robust methods for lineage-specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high-efficiency muscle lineage generation. HS conjugation to the C-terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.

Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China.

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

Blood urea nitrogen to serum albumin ratio is associated with all-cause mortality in patients with AKI: a cohort study.

Background: This study aims to investigate the relationship between blood urea nitrogen to serum albumin ratio (BAR) and all-cause mortality in patients with acute kidney injury (AKI) and evaluate the effect of BAR on the prognosis of AKI. Methods: Adult patients with AKI admitted to the ICU in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were selected in a retrospective cohort study. BAR (mg/g) was calculated using initial blood urea nitrogen (mg/dl)/serum albumin (g/dl). According to the BAR, these patients were divided into quartiles (Q1-Q4). Kaplan-Meier analysis was used to compare the mortality of the above four groups. Multivariate Cox regression analysis was used to evaluate the association between BAR and 28-day mortality and 365-day mortality. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated, and the subgroup analysis was finally stratified by relevant covariates. Results: A total of 12,125 patients with AKI were included in this study. The 28-day and 365-day mortality rates were 23.89 and 39.07%, respectively. Kaplan-Meier analysis showed a significant increase in all-cause mortality in patients with high BAR (Log-rank p < 0.001). Multivariate Cox regression analysis showed that BAR was an independent risk factor for 28-day mortality (4.32 < BAR≤7.14: HR 1.12, 95% CI 0.97-1.30, p = 0.114; 7.14 < BAR≤13.03: HR 1.51, 95% CI 1.31-1.75, p < 0.001; BAR>13.03: HR 2.07, 95% CI 1.74-2.47, p < 0.001; Reference BAR≤4.32) and 365-day mortality (4.32 < BAR≤7.14: HR 1.22, 95% CI 1.09-1.36, p < 0.001; 7.14 < BAR≤13.03: HR 1.63, 95% CI 1.46-1.82, p < 0.001; BAR>13.03: HR 2.22, 95% CI 1.93-2.54, p < 0.001; Reference BAR ≤ 4.32) in patients with AKI. The AUC of BAR for predicting 28-day mortality and 365-day mortality was 0.649 and 0.662, respectively, which is better than that of blood urea nitrogen and sequential organ failure assessment. In addition, subgroup analysis showed a stable relationship between BAR and adverse outcomes in patients with AKI. Conclusion: BAR is significantly associated with increased all-cause mortality in patients with AKI. This finding suggests that BAR may help identify people with AKI at high risk of mortality.

Clinical features, polysomnography, and genetics association study of restless legs syndrome in clinic based Chinese patients: A multicenter observational study.

STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.

Evaluation of canine adipose-derived mesenchymal stem cells for neurological functional recovery in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation. RESULTS: Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What's more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system. CONCLUSIONS: Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.

Integrated Fruit Ripeness Assessment System Based on an Artificial Olfactory Sensor and Deep Learning.

Artificial scent screening systems, inspired by the mammalian olfactory system, hold promise for fruit ripeness detection, but their commercialization is limited by low sensitivity or pattern recognition inaccuracy. This study presents a portable fruit ripeness prediction system based on colorimetric sensing combinatorics and deep convolutional neural networks (DCNN) to accurately identify fruit ripeness. Using the gas chromatography-mass spectrometry (GC-MS) method, the study discerned the distinctive gases emitted by mango, peach, and banana across various ripening stages. The colorimetric sensing combinatorics utilized 25 dyes sensitive to fruit volatile gases, generating a distinct scent fingerprint through cross-reactivity to diverse concentrations and varieties of gases. The unique scent fingerprints can be identified using DCNN. After capturing colorimetric sensor image data, the densely connected convolutional network (DenseNet) was employed, achieving an impressive accuracy rate of 97.39% on the validation set and 82.20% on the test set in assessing fruit ripeness. This fruit ripeness prediction system, coupled with a DCNN, successfully addresses the issues of complex pattern recognition and low identification accuracy. Overall, this innovative tool exhibits high accuracy, non-destructiveness, practical applicability, convenience, and low cost, making it worth considering and developing for fruit ripeness detection.