Embedded monitoring system and teaching of artificial intelligence online drug component recognition.

Drug testing has many test elements. It aims to prevent unqualified drugs from entering the market and ensure drug safety. The existing artificial intelligence (AI) online monitoring system identifies active ingredients in the process of use. Owing to their openness, data are easy to be lost, failing to meet user needs and inducing a specific impact on the use of the monitoring system. With the continuous development of computer and measurement technologies, various biochemical data are increasing at an unprecedented speed, and numerous databases are emerging. Extracting patterns from considerable known data and experimental facts is an essential task for a wide range of biological and chemical workers. Pattern recognition is one of the essential technologies for data mining. It is widely used in industry, agriculture, national defense, biomedicine, meteorology, astronomy, and other fields. To improve the effect of the online drug ingredient recognition system, this study used AI to design an online drug ingredient recognition-embedded monitoring system and applied AI to the teaching field to improve teaching efficiency. First, this study constructed the framework of the AI online drug ingredient recognition-embedded monitoring system and introduced the process of online drug ingredient recognition. Then, it introduced the pattern recognition method, constructed the pattern recognition system, and presented the pattern recognition algorithm and the algorithm evaluation index. Afterward, it used pattern recognition to conduct a qualitative analysis of the infrared spectrum of drug components and introduced the overall process of the qualitative analysis. In addition, this study employed AI to implement changes to the embedded system instruction in colleges and universities, summarizing the current issues. The impact of drug component recognition and the educational impact of embedded systems were investigated in the experimental portion. The experimental findings demonstrated the excellent accuracy, sensitivity, specificity, and Matthew correlation coefficient of the online drug component recognition-integrated monitoring system in this work. Compared with that of other systems, its average drug component recognition accuracy was above 0.85. Students in five majors reported high levels of satisfaction with the embedded system teaching, which is better for delivering college instruction.

T1-Weighted Imaging-Based Hippocampal Radiomics in the Diagnosis of Alzheimer's Disease.

RATIONALE AND OBJECTIVES: To investigate the potential of T1-weighted imaging (T1WI)-based hippocampal radiomics as imaging markers for the diagnosis of Alzheimer's disease (AD) and their efficacy in discriminating between mild cognitive impairment (MCI) and dementia in AD. METHODS: A total of 126 AD patients underwent T1WI-based magnetic resonance imaging (MRI) examinations, along with 108 age-sex-matched healthy controls (HC). This was a retrospective, single-center study conducted from November 2021 to February 2023. AD patients were categorized into two groups based on disease progression and cognitive function: AD-MCI and dementia (AD-D). T1WI-based radiomics features of the bilateral hippocampi were extracted. To diagnose AD and differentiate between AD-MCI and AD-D, predictive models were developed using random forest (RF), logistic regression (LR), and support vector machine (SVM). We compared radiomics features between the AD and HC groups, as well as within the subgroups of AD-MCI and AD-D. Area under the curve (AUC), accuracy, sensitivity, and specificity were all used to assess model performance. Furthermore, correlations between radiomics features and Mini-Mental State Examination (MMSE) scores, tau protein phosphorylated at threonine 181 (P-tau-181), and amyloid ß peptide1-42 (Aß1-42) were analyzed. RESULTS: The RF model demonstrated superior performance in distinguishing AD from HC (AUC=0.961, accuracy=90.8%, sensitivity=90.7%, specificity=90.9%) and in identifying AD-MCI and AD-D (AUC=0.875, accuracy=80.7%, sensitivity=87.2%, specificity=73.2%) compared to the other models. Additionally, radiomics features were correlated with MMSE scores, P-tau-181, and Aß1-42 levels in AD. CONCLUSION: T1WI-based hippocampal radiomics features are valuable for diagnosing AD and identifying AD-MCI and AD-D.

Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOCs) are the most common craniofacial malformation. In the complex aetiology and pathogenesis of NSOCs, genetic factors play a crucial role and IRF6, located at chromosome 1q32.2, is the best documented NSOC susceptibility gene. IRF6 is a key factor in oral maxillofacial development and known to contribute the most in NSOCs. It is essential to conduct a complete review of the existing results on IRF6 to further understand its role in the pathogenesis of NSOCs. Thus, the present authors summarised the research progress on the mechanism of IRF6 in NSOCs from both genetic and functional perspectives in this review.

Morpho-physiological and phytohormonal changes during the induction of adventitious root development stimulated by exogenous IBA application in Magnolia biondii Pamp

Abstract Magnolia biondii Pamp is an important ornamental tree species widely grown and used as a rootstock in the propagation of different Magnolia varieties. In the current studies, anatomical, physiological and endogenous hormones were studied to check the effect of IBA 750 mg/L on the adventitious rooting and to provide theoretical and technical support for the propagation of Magnolia biondii Pamp through stem cuttings. Two thousand stem cuttings were prepared and divided into two groups i.e., IBA treated cuttings and water control. For the evaluation of antioxidant enzyme activities, and endogenous hormones levels, samples were collected on the day of planting and each 5th day and further steps were carried out in the laboratory according to the protocols and proper precautions. For the anatomical observations, samples were collected on the 13th, 15th, and 17th day for IBA treated cuttings while 21st, 23rd, and 25th day for control. Collected samples were preserved in the FAA solution and further observations were carried out in the laboratory. Anatomical observations showed that it took 13 days for the differentiation of root primordia to the appearance of young adventitious roots in IBA treated cuttings, while it took 21 days to develop primordia in the control. Antioxidant enzyme activities involved in ROS were significantly higher in the IBA treated cuttings compared to control. POD showed a peak on the 13th day before the emergence of roots in IBA treated cuttings while it showed a peak on the 21st day in the control. PPO showed a peak on the 21st day in the IBA treated cuttings while it showed a peak on the 29th day in the control. SOD showed a peak on the 17th day in IBA treated cuttings, while it showed a peak on the 25th day in the control. Exogenous application of IBA enhanced the endogenous IAA and GA3 levels compared to CK, while it reduced the levels of ABA continuously at the time of rooting and then increased gradually. Inclusively, our study suggests that IBA 750 mg/L is efficient for the rooting of Magnolia biondii Pamp cuttings, as it enhanced the process of antioxidant enzyme activities, endogenous hormones levels and reduced the time of root formation which is evident from the anatomical observations.

Resumo Magnolia biondii Pamp é uma importante espécie de árvore ornamental muito cultivada e utilizada como porta-enxerto na propagação de diferentes variedades de Magnolia. Nos estudos atuais, hormônios anatômicos, fisiológicos e endógenos foram estudados para verificar o efeito do AIB na dose de 750 mg / L no enraizamento adventício e fornecer suporte teórico e técnico para a propagação de M. biondii Pamp por meio de estacas. Duas mil estacas foram preparadas e divididas em dois grupos, ou seja, tratadas com AIB e controle de água. Para a avaliação das atividades das enzimas antioxidantes e dos níveis de hormônios endógenos, as amostras foram coletadas no dia do plantio e a cada 5 dias, enquanto as demais etapas foram realizadas em laboratório de acordo com os protocolos e os devidos cuidados. Para as observações anatômicas, as amostras foram coletadas no 13º, 15º e 17º dias para estacas tratadas com AIB e no 21º, 23º e 25º dias para o controle. As amostras coletadas foram preservadas em solução FAA, e outras observações foram realizadas em laboratório. Observações anatômicas mostraram a necessidade de 13 dias para a diferenciação dos primórdios radiculares até o aparecimento de raízes adventícias jovens em estacas tratadas com AIB e de 21 dias para o desenvolvimento dos primórdios no controle. As atividades das enzimas antioxidantes envolvidas nas ROS foram significativamente maiores nas estacas tratadas com AIB em comparação com o controle. A POD apresentou pico no 13º dia antes da emergência das raízes nas estacas tratadas com AIB, enquanto no 21º dia apresentou pico no controle. A PPO teve pico no 21º dia nas estacas tratadas com AIB e no 29º dia no controle. A SOD apresentou pico no 17º dia nas estacas tratadas com AIB e no 25º dia no controle. A aplicação exógena de AIB aumentou os níveis endógenos de IAA e GA3 em relação ao controle, enquanto reduziu os níveis de ABA continuamente no momento do enraizamento e, em seguida, aumentou gradativamente. Inclusive, nosso estudo sugere que o AIB na dose de 750 mg / L é eficiente para o enraizamento de estacas de M. biondii Pamp, visto que potencializou o processo de atividades de enzimas antioxidantes e os níveis de hormônios endógenos, além de reduzir o tempo de formação de raízes, o que fica evidente nas observações anatômicas.

Morpho-physiological and phytohormonal changes during the induction of adventitious root development stimulated by exogenous IBA application in Magnolia biondii Pamp / Alterações morfofisiológicas e fito-hormonais durante a indução do desenvolvimento radicular adventício estimulado pela aplicação exógena do AIB em Magnolia biondii Pamp

Magnolia biondii Pamp is an important ornamental tree species widely grown and used as a rootstock in the propagation of different Magnolia varieties. In the current studies, anatomical, physiological and endogenous hormones were studied to check the effect of IBA 750 mg/L on the adventitious rooting and to provide theoretical and technical support for the propagation of Magnolia biondii Pamp through stem cuttings. Two thousand stem cuttings were prepared and divided into two groups i.e., IBA treated cuttings and water control. For the evaluation of antioxidant enzyme activities, and endogenous hormones levels, samples were collected on the day of planting and each 5th day and further steps were carried out in the laboratory according to the protocols and proper precautions. For the anatomical observations, samples were collected on the 13th, 15th, and 17th day for IBA treated cuttings while 21st, 23rd, and 25th day for control. Collected samples were preserved in the FAA solution and further observations were carried out in the laboratory. Anatomical observations showed that it took 13 days for the differentiation of root primordia to the appearance of young adventitious roots in IBA treated cuttings, while it took 21 days to develop primordia in the control. Antioxidant enzyme activities involved in ROS were significantly higher in the IBA treated cuttings compared to control. POD showed a peak on the 13th day before the emergence of roots in IBA treated cuttings while it showed a peak on the 21st day in the control. PPO showed a peak on the 21st day in the IBA treated cuttings while it showed a peak on the 29th day in the control. SOD showed a peak on the 17th day in IBA treated cuttings, while it showed a peak on the 25th day in the control. Exogenous application of IBA enhanced the endogenous IAA and GA3 levels compared to CK, while it reduced the levels of ABA continuously at the time of rooting and then increased gradually. Inclusively, our study suggests that IBA 750 mg/L is efficient for the rooting of Magnolia biondii Pamp cuttings, as it enhanced the process of antioxidant enzyme activities, endogenous hormones levels and reduced the time of root formation which is evident from the anatomical observations.

Magnolia biondii Pamp é uma importante espécie de árvore ornamental muito cultivada e utilizada como porta-enxerto na propagação de diferentes variedades de Magnolia. Nos estudos atuais, hormônios anatômicos, fisiológicos e endógenos foram estudados para verificar o efeito do AIB na dose de 750 mg / L no enraizamento adventício e fornecer suporte teórico e técnico para a propagação de M. biondii Pamp por meio de estacas. Duas mil estacas foram preparadas e divididas em dois grupos, ou seja, tratadas com AIB e controle de água. Para a avaliação das atividades das enzimas antioxidantes e dos níveis de hormônios endógenos, as amostras foram coletadas no dia do plantio e a cada 5 dias, enquanto as demais etapas foram realizadas em laboratório de acordo com os protocolos e os devidos cuidados. Para as observações anatômicas, as amostras foram coletadas no 13º, 15º e 17º dias para estacas tratadas com AIB e no 21º, 23º e 25º dias para o controle. As amostras coletadas foram preservadas em solução FAA, e outras observações foram realizadas em laboratório. Observações anatômicas mostraram a necessidade de 13 dias para a diferenciação dos primórdios radiculares até o aparecimento de raízes adventícias jovens em estacas tratadas com AIB e de 21 dias para o desenvolvimento dos primórdios no controle. As atividades das enzimas antioxidantes envolvidas nas ROS foram significativamente maiores nas estacas tratadas com AIB em comparação com o controle. A POD apresentou pico no 13º dia antes da emergência das raízes nas estacas tratadas com AIB, enquanto no 21º dia apresentou pico no controle. A PPO teve pico no 21º dia nas estacas tratadas com AIB e no 29º dia no controle. A SOD apresentou pico no 17º dia nas estacas tratadas com AIB e no 25º dia no controle. A aplicação exógena de AIB aumentou os níveis endógenos de IAA e GA3 em relação ao controle, enquanto reduziu os níveis de ABA continuamente no momento do enraizamento e, em seguida, aumentou gradativamente. Inclusive, nosso estudo sugere que o AIB na dose de 750 mg / L é eficiente para o enraizamento de estacas de M. biondii Pamp, visto que potencializou o processo de atividades de enzimas antioxidantes e os níveis de hormônios endógenos, além de reduzir o tempo de formação de raízes, o que fica evidente nas observações anatômicas.

Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development.

With the continuous development of the pharmaceutical industry, people have always paid attention to the safety and effectiveness of drugs, including innovative drugs and generic drugs. For pharmaceutical companies as manufacturers, drug development is a very lengthy process that requires high costs, millions of man-hours, thousands of trials, and the mobilization of hundreds of researchers. Therefore, efforts need to be made to develop drugs with high safety and effectiveness. Drug research and development plays an important role today. Based on this, this article applied computer molecular simulation embedded technology and artificial intelligence technology to drug research and development. First, the problems faced in the research and development of anti-inflammatory disease-dependent tumor drugs were introduced, and then the applications of computer molecular simulation embedded technology and artificial intelligence technology in drug research and development were analyzed. Subsequently, the application of artificial intelligence in drug research and development teaching was analyzed, and a teaching system based on computer molecular simulation embedded technology and artificial intelligence was designed. Finally, the application effects of computer molecular simulation embedded technology and artificial intelligence technology were analyzed, and a feasible conclusion was drawn. The use of computer molecular simulation embedded technology and artificial intelligence technology can greatly improve the efficiency of drug research and development, and the research and development safety of imatinib mesylate has been improved by 7%. On the other hand, it can improve students' learning interest and stimulate their learning interest, and students' drug research and development capabilities have been improved. Drug research and development for inflammatory-dependent tumors has good application prospects.

Physiological Function of RDL1 and RDL2 Subunits of the Ionotropic GABA Receptor in the Spodoptera litura with the CRISPR/Cas9 System In Vivo.

In insect ionotropic γ-aminobutyric acid receptor (iGABAR) subunits, only resistance to dieldrin (RDL) can be individually and functionally expressed in vitro. In lepidopteran, two to three RDL subtypes are identified; however, their physiological roles have not been distinguished in vivo. In this study, SlRdl1 and SlRdl2 of S. litura were individually knocked out using CRISPR/Cas9, respectively. The mortality and larval and pupal duration of KOSlRdl1 and KOSlRdl2 were increased. The flight time and distance were increased by 43.30%-80.66% and 58.96%-198.22%, respectively, in KOSlRdl1. The GABA-induced current was significantly decreased by 53.57%-74.28% and 46.91%-63.34% in the ventral nerve cord, and the GABA titer was significantly reduced by 17.65%-28.05% and 19.85%-42.46% in KOSlRdl1 and KOSlRdl2, respectively. In conclusion, SlRdl1 and SlRdl2 are necessary for the transmission of GABA-induced neural signals; however, only SlRdl1 could regulate the flight capability of S. litura. Our results provided a new avenue to study lepidopteran iGABARs.

Effect of e-health interventions on HIV prevention: a protocol of systematic review and meta-analysis.

BACKGROUND: Global epidemiological data indicates that despite implementation of multiple interventions and significant financial investment, the HIV/AIDS epidemic remained inadequately controlled as of 2020. E-health presents a novel approach in delivering health information and health care and has gained popularity in HIV prevention worldwide. However, evidence on the effectiveness of e-health interventions on HIV prevention among diverse populations remains inadequate. Our study aims to systematically evaluate the effectiveness of varying e-health interventions on HIV prevention, with the objective of providing data support and guidance for the development of future e-health HIV intervention strategies. METHODS: A systematic search of electronic English databases, including MEDLINE through PubMed, Embase, Scopus, and Web of Science, along with three Chinese databases, including National Knowledge Infrastructure (CNKI), Chinese Wanfang Digital Periodicals (WANFANG), and Chinese Science and Technology Periodicals (VIP) database, will be conducted for the period of 1 January 1980 to 31 December 2022. Additionally, gray literature and unpublished trials in trial registers will be searched. Studies aimed at HIV prevention through e-health interventions, with full-text publications available in either English or Chinese, will be included. Study types will be limited to RCT, cluster RCT, and quasi-experiment study. The risk of bias in individual studies will be assessed following the guideline highlighted by the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes will cover cognitive, behavioral, psychological, management, and biological measures of individuals involved in e-health interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Ultimately, a systematic review with meta-analysis will be conducted to compare the effectiveness of e-health interventions among diverse populations. DISCUSSION: This systematic review seeks to establish novel insights into the effectiveness of e-health interventions in diverse populations worldwide. It will inform the design and use of e-health interventions to optimize HIV-related strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022295909.

Identification of putative regulatory single-nucleotide variants in NTN1 gene associated with NSCL/P.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common polygenetic disease. Although genome-wide association studies (GWAS) identified NTN1 gene as a high-priority candidate of NSCL/P, the comprehensive genetic architecture of NTN1 weren't yet known. Thus, this study aimed to determine full-scale genetic variants of NTN1 for NSCL/P in Chinese Han people. Initially, targeted sequencing of NTN1 gene was performed on 159 NSCL/P patients to identify susceptible single nucleotide polymorphisms (SNPs) associated with NSCL/P. Then, association analysis and burden analysis were separately used to validate the common variants and rare variants identified among large size of samples (1608 NSCL/P cases and 2255 controls). Additionally, NSCL/P subtype association analysis was applied to elucidate the etiology discrepancy of non-syndromic cleft lip with palate (NSCLP) and non-syndromic cleft lip only (NSCLO). Lastly, bioinformatics analysis was performed to annotate and prioritize candidate variants. We found 15 NSCL/P-associated SNPs including rs4791774 (P = 1.10E-08, OR = 1.467, 95% CI: 1.286~1.673) and rs9788972 (P = 1.28E-07, OR = 1.398, 95% CI : 1.235~1.584) originally detected by previous GWASs in Chinese Han ancestry. Four NSCLO risk-associated SNPs and eight specific NSCLP associated SNPs were found. Three SNPs (rs4791331, rs4791774 and rs9900753) were predicted to locate at regulatory region of NTN1. Our study validated the association between NTN1 gene and pathogenesis of NSCL/P and reinforced the hypothesis that NSCLP have a different etiology from NSCLO. We also identified three putative regulatory SNPs in NTN1 gene.

An automatic and accurate deep learning-based neuroimaging pipeline for the neonatal brain.

BACKGROUND: Accurate segmentation of neonatal brain tissues and structures is crucial for studying normal development and diagnosing early neurodevelopmental disorders. However, there is a lack of an end-to-end pipeline for automated segmentation and imaging analysis of the normal and abnormal neonatal brain. OBJECTIVE: To develop and validate a deep learning-based pipeline for neonatal brain segmentation and analysis of structural magnetic resonance images (MRI). MATERIALS AND METHODS: Two cohorts were enrolled in the study, including cohort 1 (582 neonates from the developing Human Connectome Project) and cohort 2 (37 neonates imaged using a 3.0-tesla MRI scanner in our hospital).We developed a deep leaning-based architecture capable of brain segmentation into 9 tissues and 87 structures. Then, extensive validations were performed for accuracy, effectiveness, robustness and generality of the pipeline. Furthermore, regional volume and cortical surface estimation were measured through in-house bash script implemented in FSL (Oxford Centre for Functional MRI of the Brain Software Library) to ensure reliability of the pipeline. Dice similarity score (DSC), the 95th percentile Hausdorff distance (H95) and intraclass correlation coefficient (ICC) were calculated to assess the quality of our pipeline. Finally, we finetuned and validated our pipeline on 2-dimensional thick-slice MRI in cohorts 1 and 2. RESULTS: The deep learning-based model showed excellent performance for neonatal brain tissue and structural segmentation, with the best DSC and the 95th percentile Hausdorff distance (H95) of 0.96 and 0.99 mm, respectively. In terms of regional volume and cortical surface analysis, our model showed good agreement with ground truth. The ICC values for the regional volume were all above 0.80. Considering the thick-slice image pipeline, the same trend was observed for brain segmentation and analysis. The best DSC and H95 were 0.92 and 3.00 mm, respectively. The regional volumes and surface curvature had ICC values just below 0.80. CONCLUSIONS: We propose an automatic, accurate, stable and reliable pipeline for neonatal brain segmentation and analysis from thin and thick structural MRI. The external validation showed very good reproducibility of the pipeline.

Cyanobacteria blooms induced precipitation of calcium carbonate and dissolution of silica in a subtropical lagoon, Florida Bay, USA.

In recent decades, annual cyanobacteria blooms in Florida Bay displayed spatial and temporal patterns that are consistent with changes in alkalinity and dissolved silicon in water. In early summer, the blooms developed in the north-central bay and spread southward in fall. The blooms drew down dissolved inorganic carbon and increased water pH, causing in situ precipitation of calcium carbonate. Dissolved silicon concentrations in these waters were at minimum in spring (20-60 µM), increased during summer, and reached an annual maximum (100-200 µM) during late summer. The dissolution of silica as a result of high pH in bloom water was first observed in this study. During the peak of blooms, silica dissolution in Florida Bay varied from 0.9 × 107 to 6.9 × 107 mol per month over the study period, depending on the extent of cyanobacteria blooms in a given year. Concurrent calcium carbonate precipitations in the cyanobacteria bloom region are between 0.9 × 108 and 2.6 × 108 mol per month. It is estimated that 30-70% of atmospheric CO2 uptake in bloom waters was precipitated as calcium carbonate mineral and remainders of CO2 influx were used for the production of biomass.

Integrated Analysis of the Association Between Variants at PAX7 and NSCL/P in the Han Population.

OBJECTIVE: Paired box 7 (PAX7) has been considered as a candidate gene for non-syndromic cleft lip with or without palate (NSCL/P). However, there is no research for the XXX, and previous studies concentrated on limited variants. This study aimed to conduct sufficiently dense and powerful scans of variants at PAX7 and explored the roles of variants at PAX7 in NSCL/P among the XXX. DESIGN: Targeted region sequencing was performed to thoroughly screen variations, followed by a two-phase association analysis. 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. We also explored the roles of variants at PAX7 gene in NSCL/P subtypes. Additionally, indirect associations were found by calculating LD and haplotypes. SETTING: The study was conducted in XXX. PATIENTS, PARTICIPANTS: 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. INTERVENTIONS: Blood samples were collected. MAIN OUTCOME MEASURES: To explore the association analysis between variants at PAX7 and NSCL/P in XXX. RESULTS: The results showed that rs2236810, rs114882979 and rs2236804 were significantly associated with NSCL/P, which were predicted to have regulatory functions. Besides, variants at PAX7 function differently in the NSCL/P subtypes. We also discovered a PAX7 missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T). CONCLUSIONS: In summary, we confirmed 3 SNPs at PAX7 were significantly associated with NSCL/P in XXX and identified a missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T).

Causal Variations at IRF6 Gene Identified in Van der Woude Syndrome Pedigrees.

The purpose of this study is to analyze the clinical characteristics of patients with Van der Woude syndrome (VWS) and to detect variations in each patient. Finally, the combination of genotype and phenotype can make a clear diagnosis of VWS patients with different phenotype penetrance.Five Chinese VWS pedigree were enrolled. Whole exome sequencing of the proband was performed, and the potential pathogenic variation was further verified by Sanger sequencing in the patient and their parents. The human mutant IRF6 coding sequence was generated from the human full-length IRF6 plasmid by site-directed mutagenesis and cloned into the GV658 vector, RT-qPCR and Western blot were used to detect the expression of IRF6.We found one de novo nonsense variation (p. Gln118Ter) and three novel missense variations (p. Gly301Glu, p. Gly267Ala, and p. Glu404Gly) co-segregated with VWS. RT-qPCR analysis revealed that p. Glu404Gly significantly reduced the expression level of IRF6 mRNA. Western blot of cell lysates confirmed that IRF6 p. Glu404Gly abundance levels were lower than those for IRF6 wild type.This discovery of the novel variation (IRF6 p. Glu404Gly) expands the spectrum of known variations in VWS in Chinese humans. Genetic results combined with clinical phenotypes and differential diagnosis points from other diseases can make a definitive diagnosis and provide genetic counseling for families.

DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson's disease.

DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

Factors associated with gastrointestinal stromal tumor rupture and pathological risk: A single-center retrospective study.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare gastrointestinal mesenchymal tumor with potential malignancy. Once the tumor ruptures, regardless of tumor size and mitotic number, it can be identified into a high-risk group. It is of great significance for the diagnosis, treatment, and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor. AIM: To identify the factors associated with GIST rupture and pathological risk. METHODS: A cohort of 50 patients with GISTs, as confirmed by postoperative pathology, was selected from our hospital. Clinicopathological and computed tomography data of the patients were collected. Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade. RESULTS: Pathological risk grade, tumor diameter, tumor morphology, internal necrosis, gas-liquid interface, and Ki-67 index exhibited significant associations with GIST rupture (P < 0.05). Gender, tumor diameter, tumor rupture, and Ki-67 index were found to be correlated with pathological risk grade of GIST (P < 0.05). Multifactorial logistic regression analysis revealed that male gender and tumor diameter ≥ 10 cm were independent predictors of a high pathological risk grade of GIST [odds ratio (OR) = 11.12, 95% confidence interval (95%CI): 1.81-68.52, P = 0.01; OR = 22.96, 95%CI: 2.19-240.93, P = 0.01]. Tumor diameter ≥ 10 cm, irregular shape, internal necrosis, gas-liquid interface, and Ki-67 index ≥ 10 were identified as independent predictors of a high risk of GIST rupture (OR = 9.67, 95%CI: 2.15-43.56, P = 0.01; OR = 35.44, 95%CI: 4.01-313.38, P < 0.01; OR = 18.75, 95%CI: 3.40-103.34, P < 0.01; OR = 27.00, 95%CI: 3.10-235.02, P < 0.01; OR = 4.43, 95%CI: 1.10-17.92, P = 0.04). CONCLUSION: Tumor diameter, tumor morphology, internal necrosis, gas-liquid, and Ki-67 index are associated with GIST rupture, while gender and tumor diameter are linked to the pathological risk of GIST. These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions / 医学前沿

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

Targeted re-sequencing on 1p22 among non-syndromic orofacial clefts from Han Chinese population.

Rs560426 at 1p22 was proved to be associated with NSCL/P (non-syndromic cleft lip with or without the palate) in several populations, including Han Chinese population. Here, we conducted a deep sequencing around rs560426 to locate more susceptibility variants in this region. In total, 2,293 NSCL/P cases and 3,235 normal controls were recruited. After sequencing, association analysis was performed. Western blot, RT-qPCR, HE, immunofluorescence staining, and RNA sequencing were conducted for functional analyses of the selected variants. Association analysis indicated that rs77179923 was the only SNP associated with NSCLP specifically (p = 4.70E-04, OR = 1.84), and rs12071152 was uniquely associated with LCLO (p = 4.00E-04, OR = 1.30, 95%CI: 1.12-1.51). Moreover, de novo harmful rare variant NM_004815.3, NP_004806.3; c.1652G>C, p.R551T in ARHGAP29 resulted in a decreased expression level of ARHGAP29, which in turn affected NSCL/P-related biological processes; however, no overt cleft palate (CP) phenotype was observed. In conclusion, rs12071152 was a new susceptible variant, which is specifically associated with LCLO among the Han Chinese population. Allele A of it could increase the risk of having a cleft baby. Rs77179923 and rare variant NM_004815.3, NP_004806.3; c.1652G>C, p.R551T at 1p22 were both associated with NSCLP among the Han Chinese population. However, this missense variation contributes to no overt CP phenotype due to dosage insufficiency or compensation from other genes.

Evaluation of a new method of calculating breast tumor volume based on automated breast ultrasound.

Objective: To evaluate the effectiveness and advantages of a new method for calculating breast tumor volume based on an automated breast ultrasound system (ABUS). Methods: A total of 42 patients (18-70 years old) with breast lesions were selected for this study. The Ivenia ABUS 2.0 (General Electric Company, USA) was used, with a probe frequency of 6-15 MHz. Adobe Photoshop CS6 software was used to calculate the pixel ratio of each ABUS image, and to draw an outline of the tumor cross-section. The resulting area (in pixels) was multiplied by the pixel ratio to yield the area of the tumor cross-section. The Wilcoxon signed rank test and Bland-Altman plot were used to compare mean differences and mean values, respectively, between the two methods. Results: There was no significant difference between the tumor volumes calculated by pixel method as compared to the traditional method (P>0.05). Repeated measurements of the same tumor volume were more consistent with the pixel method. Conclusion: The new pixel method is feasible for measuring breast tumor volume and has good validity and measurement stability.