An Innovative and Efficient Fluorescent Detection Technique for Salmonella in Animal-Derived Foods Using the CRISPR/Cas12a-HCR System Combined with PCR/RAA.

Here, we present a method for Salmonella detection using clustered regularly interspaced short palindromic repeats associated with the CRISPR-associated protein 12a-hybridization chain reaction (CRISPR/Cas12a-HCR) system combined with polymerase chain reaction/recombinase-assisted amplification (PCR/RAA) technology. The approach relies on the Salmonella invA gene as a biorecognition element and its amplification through PCR and RAA. In the presence of the target gene, Cas12a, guided by crRNA, recognizes and cleaves the amplification product, initiating the HCR. Fluorescently labeled single-stranded DNA (ssDNA) H1 and H2 were introduced, and the Salmonella concentration was determined based on the fluorescence intensity from the triggered HCR. Both assays demonstrate high specificity, sensitivity, simplicity, and rapidity. The detection range was 2 × 101-2 × 109 CFU/mL, with an LOD of 20 CFU/mL, and the entire process enabled specific and rapid Salmonella detection within 85-105 min. Field-incurred spiked recovery tests were conducted in mutton and beef samples using both assays, demonstrating satisfactory recovery and accuracy in animal-derived foods. By combining CRISPR/Cas12a with hybridization chain reaction technology, this study presents a rapid and sensitive Salmonella detection method that is crucial for identifying pathogenic bacteria and monitoring food safety.

Facile fabricate sandwich-structured molecularly imprinted dopamine polymer for simultaneously specific capture of Low-density lipoprotein and eliminate "bad cholesterol".

A simplified approach for preparation of sandwich type molecularly imprinted polymers (PPDA-MIPs) is proposed for simultaneously identify Low-density lipoprotein (LDL) and dispose "bad cholesterol". Porous polydopamine nanosphere (PPDA) is applied as a matrix for immobilization of LDL, and the imprinted layer is formed by dopamine acting as a functional monomer. Since imprinted cavities exhibit shape memory effects in terms of recognizing selectivity, the PPDA-MIPs exhibit excellent selectivity toward LDL and a substantial binding capacity of 550.3 µg mg-1. Meanwhile, six adsorption/desorption cycles later, the adsorption efficiency of 83.09 % is still achieved, indicating the adequate stability and reusability of PPDA-MIPs. Additionally, over 80 % of cholesterol is recovered, indicating the completeness of "bad cholesterol" removal in LDL. Lastly, as demonstrated by gel electrophoresis, PPDA-MIPs performed satisfactory behavior for the removal of LDL from the goat serum sample.

[Analysis of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus due to variants of SCN1A gene].

OBJECTIVE: To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Three GEFS+ probands and their pedigree members presented at the Children's Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants. RESULTS: Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c.1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c.2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c.1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION: The c.1613T>C, c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

Research progress on natural preservatives of meat and meat products: classifications, mechanisms and applications.

Meat and meat products are highly susceptible to contamination by microorganisms and foodborne pathogens, which cause serious economic losses and health hazards. The large consumption and waste of meat and meat products means that there is a need for safe and effective preservation methods. Furthermore, toxicological aspects of chemical preservation techniques related to major health problems have sparked controversies and have prompted consumers and producers to turn to natural preservatives. Consequently, natural preservatives are being increasingly used to ensure the safety and quality of meat products as a result of customer preferences and biological efficacy. However, information on the current status of these preservatives is scattered and a comprehensive review is lacking. Here, we review current knowledge on the classification, mechanisms of natural preservatives and their applications in the preservation of meat and meat products, and also discuss the potential of natural preservatives to improve the safety of meat and meat products. The current status and the current research gaps in the extraction, application and controlled-release of natural antibacterial agents for meat preservation are also discussed in detail. This review may be useful to the development of efficient food preservation techniques in the meat industry. © 2024 Society of Chemical Industry.

Chitosan-Enhanced pH-Sensitive Anthocyanin Indicator Film for the Accurate Monitoring of Mutton Freshness.

Natural anthocyanin indicator films with an excellent pH response enable the visual assessment of meat freshness. In this investigation, chitosan was initially employed as a colorimetric enhancer, leading to the development of a pH-sensitive indicator film that was enhanced in colorimetry. The characteristics of this indicator film were thoroughly analyzed, and the mechanism responsible for the increased sensitivity of anthocyanin within the chitosan matrix, as indicated by the color response, was elucidated. The recrystallization of chitosan impeded the hydration of AH+ as the pH increased from 6.0 to 8.0, leading to distinct color changes. Moreover, the application of this indicator film was extended to the monitoring of mutton meat freshness. It facilitated the differentiation of mutton meat into three distinct stages, namely, fresh, sub-fresh, and spoiled, based on alterations in color. Additionally, a robust positive correlation was established between the color difference value of the indicator film and the total volatile basic nitrogen and bacterial count of the mutton meat, enabling quantitative analysis. The present study, therefore, demonstrated a novel function of chitosan, i.e., the enhancement of the color of anthocyanin, which could be useful in designing and fabricating indicator films with a high color response.

Fabrication of carvacrol loaded cellulose acetate phthalate/shellac composite film and its application to mackerel fillets preservation.

In this research, the carvacrol (CAR) loaded cellulose acetate phthalate (CAP) /shellac (SH) films were prepared via electrostatic repulsion strategy and casting method. The CAP/SH-CAR films demonstrated excellent tensile strength, while also exhibiting good UV light barrier and thermal stability. The results showed that the addition of CAR significantly improved the barrier of the CAP film to water vapor and oxygen permeability. When the addition amount of CAR was 0.9 % (w/w) with respect to CAP content, the CAP/SH-CAR films exhibited good antibacterial activity and effectively reduced the growth of S. aureus and E. coli by approximately 47.9 % and 50.9 %, respectively. The presence of SH improved the retention rate of CAR in CAP/SH-CAR films, with the retention rate ranging from 45.2 to 56.8 %. Finally, the CAP/SH-CAR films were applied to preserve the mackerel fillets, indicating that the rate of freshness deterioration had been delayed and showing a good freshness preservation effect. Therefore, the CAP/SH-CAR films have the potential to be used as food packaging materials.

Superabsorbent carboxymethyl cellulose-based hydrogel fabricated by liquid-metal-induced double crosslinking polymerisation.

Herein, we introduced a liquid-metal/polymerisable deep eutectic solvent (LM/PDES) system to the carboxymethyl cellulose (CMC) and acrylic acid solution to prepare a double-cross-linked CMC-polyacrylic acid (PAA)-LM/PDES superabsorbent hydrogel via graft crosslinking polymerisation for 5 min. FTIR and XRD provided evidence for the coordinate crosslinking between Ga3+ and carboxy groups in the CMC-PAA-LM/PDES gel structure and chemical crosslinking between CMC and PAA components. The pore size of the obtained hydrogels gradually decreases with the increase of LM-AA/PDES content. The rigid CMC polysaccharide chains increased the distance between the ionic groups on the flexible PAA molecular chains, resulting in high osmotic pressure. In addition, the synergistic effects of hydrophilic groups, electrostatic repulsion, macroporous structures and double crosslinking on the CMC and PAA structures provided a driving force and space for the gel to absorb electrolyte containing liquid. The absorption capacity of the CMC-PAA-LM/PDES gel for physiological saline reached 97 g/g, which exceeded that of a single cross-linked CMC-PAA gel and a reported superabsorbent material (71 g/g). This work solved the problem of long heating times and insufficient mechanical properties for the preparation of superabsorbent gels, providing a theoretical reference for improving the absorption capacity of superabsorbent materials for electrolyte-containing aqueous solutions.

A Combined Manual Annotation and Deep-Learning Natural Language Processing Study on Accurate Entity Extraction in Hereditary Disease Related Biomedical Literature.

We report a combined manual annotation and deep-learning natural language processing study to make accurate entity extraction in hereditary disease related biomedical literature. A total of 400 full articles were manually annotated based on published guidelines by experienced genetic interpreters at Beijing Genomics Institute (BGI). The performance of our manual annotations was assessed by comparing our re-annotated results with those publicly available. The overall Jaccard index was calculated to be 0.866 for the four entity types-gene, variant, disease and species. Both a BERT-based large name entity recognition (NER) model and a DistilBERT-based simplified NER model were trained, validated and tested, respectively. Due to the limited manually annotated corpus, Such NER models were fine-tuned with two phases. The F1-scores of BERT-based NER for gene, variant, disease and species are 97.28%, 93.52%, 92.54% and 95.76%, respectively, while those of DistilBERT-based NER are 95.14%, 86.26%, 91.37% and 89.92%, respectively. Most importantly, the entity type of variant has been extracted by a large language model for the first time and a comparable F1-score with the state-of-the-art variant extraction model tmVar has been achieved.

Recent studies on proteins and polysaccharides-based pH-responsive fluorescent materials.

Polymer-based pH-responsive fluorescent materials have the characteristics of fast response, real-time monitoring, visualisation, and easy forming. Consequently, they have attracted widespread attention in wound healing, sweat monitoring, security and anti-counterfeiting, freshness detection of aquatic products, metal-ion sensing and bioimaging. This paper analyses the preparation principles and characteristics of pH-responsive fluorescent materials based on cellulose, chitosan and proteins. It then outlines the fluorescence properties, environmental response mechanisms and applications of various luminescent materials. Next, the research indicates that amines, N-heterocyclic rings, carboxyl groups and amino plasmonic groups on the fluorescent molecule structure and polymer skeleton appear to change the degree of ionisation under acid or alkali stimulation, which affects the light absorption ability of chromophore electrons, thus producing fluorescence changes in fluorescent materials under different pH stimuli. On this basis, the challenges and growth encountered in the development of proteins and polysaccharides-based pH-responsive fluorescent materials were prospected to provide theoretical references and technical support for constructing pH-responsive fluorescent materials with high stability, high sensitivity, long-lasting pH-response and wide detection range.

Hypermethylated CDO1 and CELF4 in cytological specimens as triage strategy biomarkers in endometrial malignant lesions.

Objective: Developing a non-invasive and reliable triage test for endometrial malignant lesions is an important goal, as it could help to reduce the number of invasive diagnostic procedures required and improve patient survival. We aimed to estimate the diagnostic value of DNA methylation levels in cervical cytological samples of endometrial cancer (EC) and endometrial atypical hyperplasia (AH). Methods: A total of 607 women who had indications for endometrial biopsy in the Department of Obstetrics and Gynecology of Cangzhou Central Hospital from October 2022 to April 2023 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before endometrial biopsy. Clinical information, tumor biomarkers, and endometrial thickness (ET) of transvaginal ultrasonography (TVS) were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial malignant lesions. The role of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4) gene methylation as a triage strategy biomarker in endometrial malignant lesions was specifically explored. Results: Multivariate logistic regression analysis showed that premenopausal ET ≥ 11 mm or postmenopausal ET ≥ 5 mm, CDO1 ΔCt ≤ 8.4, or CELF4 ΔCt ≤ 8.8 were the risk factors for AH and EC, with odds ratios (ORs) (95%CI) of 5.03 (1.83-13.82) and 6.92 (1.10-43.44), respectively (p-values < 0.05). The sensitivity and specificity of CDO1/CELF4 dual-gene methylation assay for AH and EC reached 84.9% (95%CI: 75.3%-94.5%) and 86.6% (95%CI: 83.8%-89.5%), respectively. ET combined with DNA methylation detection further improved the specificity to (94.9%, 95%CI: 93.1%-96.8%). Conclusion: The accuracy of cervical cytology DNA methylation is superior to that of other clinical indicators in the non-invasive examination of endometrial malignant lesions. DNA methylation combined with TVS can further improve the specificity and is a promising biomarker triage strategy in women with suspected endometrial lesions.

Freezing of water and melting of ice: theoretical modeling at the nanoscale.

Freezing of water and melting of ice at the nanoscale play critical roles in science and technology fields, including aviation systems, infrastructures, and other broad spectrum of technologies. To cope with the icing challenge, nanoscale anti-icing surface technology has been developed. The freezing and melting temperatures can be tailored by manipulating the size (the radius of water or ice); however, it lacks systemic research. In this work, the size effect on the melting temperature of ice nanocrystals was first established, which considered the variation of bond energy and equivalent heat energy from the perspective of the force-heat equivalence energy density principle. Based on the heterogeneous nucleation mode and by further considering the size and temperature effects on the interface energy involved solid-liquid energy and liquid-vapor energy as well as the above developed melting temperature model, another model is established to accurately predict the freezing temperature of water nanodroplets. The parameters required by the two models established in this paper have a clear physical meaning and establish the quantitative relationships among freezing temperature, melting temperature, surface stress, interface energy, and other thermodynamic parameters. The agreement between model prediction and experimental simulation data confirms the validity and universality of the established models. The higher prediction accuracy of this work compared to the other theoretical models, due to the more detailed consideration and the reference point, captures the errors introduced by the experiment or simulation. This study contributes to a deeper understanding of the underlying mechanism of freezing of water and melting of ice nanocrystals and provides theoretical guidance for the design of cryopreservation systems and anti-icing systems for aviation.

Co-teaching in medicine and nursing in training nurse anesthetists: a before-and-after controlled study.

BACKGROUND: Clarifying the effectiveness of co-teaching in medicine and nursing (CMN) is important as it is crucial in clinical practice to improve the quality of patient care and prognosis. In this study, we aimed to determine the efficacy of CMN in nurse anesthetist training. METHOD: The study comprised a 6-month training session and a before-and-after controlled study. In total, 59 nurses were recruited. The first 30 nurses were enrolled in the conventional single-teaching in nursing (SN) group and only took nursing-related courses. The next 29 students were enrolled in the CMN group and received both general medical and nursing-specific curricula. Before and after training, medical and nursing collaboration competency scores and knowledge scores were compared between the two groups. At the end of the study, qualitative comments on teaching satisfaction and clinical reasoning skills improvement were queried, and content analysis was performed. RESULTS: Participants in the CMN group outperformed those in the SN group in tests of medical and nursing collaboration abilities as well as knowledge. The CMN group outperformed the SN group in terms of teaching satisfaction evaluation, particularly in terms of fostering learning in the anesthetist specialty, improving clinical practice, fostering motivation, and influencing how people think about challenges at work. Furthermore, participants in the CMN group felt that their clinical reasoning abilities had improved. CONCLUSION: In comparison to the SN group, the CMN group had enhanced outcomes of patient care, medical and nursing collaboration, and clinical reasoning skills.

A Review of Chondroitin Sulfate's Preparation, Properties, Functions, and Applications.

Chondroitin sulfate (CS) is a natural macromolecule polysaccharide that is extensively distributed in a wide variety of organisms. CS is of great interest to researchers due to its many in vitro and in vivo functions. CS production derives from a diverse number of sources, including but not limited to extraction from various animals or fish, bio-synthesis, and fermentation, and its purity and homogeneity can vary greatly. The structural diversity of CS with respect to sulfation and saccharide content endows this molecule with distinct complexity, allowing for functional modification. These multiple functions contribute to the application of CS in medicines, biomaterials, and functional foods. In this article, we discuss the preparation of CS from different sources, the structure of various forms of CS, and its binding to other relevant molecules. Moreover, for the creation of this article, the functions and applications of CS were reviewed, with an emphasis on drug discovery, hydrogel formation, delivery systems, and food supplements. We conclude that analyzing some perspectives on structural modifications and preparation methods could potentially influence future applications of CS in medical and biomaterial research.

Synthesis, characterization and application of oligomeric proanthocyanidin-rich dual network hydrogels.

A structurally dense hydrogel, with strong hydrogen bonding networks, was formed from poly(vinyl alcohol), sodium alginate, and oligomeric proanthocyanidins, using a combination of freeze-thaw cycles and calcium ion cross-linking. The structure of the hydrogel was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Mechanical testing and thermogravimetric analysis showed that incorporation of proanthocyanidins enhanced both the mechanical properties and the thermal stability of the hydrogel. The hydrogel was also demonstrated to have excellent ultraviolet resistance and antioxidant properties. The hydrogel was further shown that this hydrogel is also capable of generating electrochemical reactions, which strongly suggests that this hydrogel has exciting potential in many fields.

Unveiling heterocyclic aromatic amines (HAAs) in thermally processed meat products: Formation, toxicity, and strategies for reduction - A comprehensive review.

This comprehensive review focuses on heterocyclic aromatic amines (HAAs), a class of chemicals that commonly form during the cooking or processing of protein-rich foods. The International Agency for Research on Cancer (IARC) has categorized certain HAAs as probable human carcinogens, highlighting the significance of studying their formation and control in food safety research. The main objective of this review is to address the knowledge gaps regarding HAAs formation and propose approaches to reduce their potential toxicity during thermal processing. By summarizing the mechanisms involved in HAAs formation and inhibition, the review encompasses both conventional and recent detection methods. Furthermore, it explores the distribution of HAAs in thermally processed meats prepared through various cooking techniques and examines their relative toxicity. Additionally, considering that the Maillard reaction, responsible for HAAs formation, also contributes to the unique flavors and aromas of cooked meat products, this review investigates the potential effects of inhibiting HAAs formation on flavor substances. A thorough understanding of these complex interactions provides a foundation for developing targeted interventions to minimize the formation of HAAs and other harmful compounds during food processing.

Structural characterization of cell-wall polysaccharides purified from chayote (Sechium edule) fruit.

Chayote (Sechium edule), an underutilized cucurbit vegetable crop, has gained attention as it exhibits health-promoting properties. However, the primary structure of chayote cell-wall polysaccharides has not been comprehensively studied. In this study, two cell-wall polysaccharides, CP-1 (41.1 KDa) and CP-2 (15.6 KDa), were extracted from chayote, and the structural analysis of CP-1 and CP-2 was carried out by monosaccharide composition analysis, Fourier transform infrared spectroscopy (FTIR), methylation analysis, and nuclear magnetic resonance spectroscopy (NMR). The results demonstrated that CP-1 was a galactan, and CP-2 was an anionic heteropolysaccharide composed of galacturonic acid, galactose, arabinose, rhamnose, glucose, glucuronic acid, mannose, and xylose in the molar ratio of 31.2:26.3:24.9:7.4:6.5:1.9:1.3:0.5. CP-2 has a backbone of â†’ 4)-ß-d-Galp-(1 â†’ 3,6)-ß-d-Galp-(1 â†’ 3)-ß-d-Galp-(1 â†’ 4)-α-d-GalpA-(1→, with branches at O-6 of â†’ 3,6)-ß-d-Galp-(1→, consisting of α-l-Araf-(1 â†’ 5)-α-l-Araf-(1 â†’ 4)-ß-d-Glcp-(1 â†’. Analysis of the structural and physicochemical properties confirmed the excellent application characteristics of CP-1 and CP-2. Hence, cell-wall polysaccharides of chayote could be used as new polysaccharides materials.

Physicochemical characterization, digestion profile and gut microbiota regulation activity of intracellular polysaccharides from Chlorella zofingiensis.

A number of studies have shown that the polysaccharides from microalgae exhibit diverse biological activities, however, little is known about their digestibility and impact on human gut microbiota. In this study, a simulating digestion and fermentation system were established to investigate the digestibility and fermentation of intracellular polysaccharides from Chlorella zofingiensis (CZIP-S3). The results indicated that CZIP-S3 is a macromolecular polysaccharide composed of mannose, glucose, galactose and rhamnose, consisting of a main chain and two branched repeating units. CZIP-S3 could not be digested in the upper gastrointestinal tract. However, CZIP-S3 could be metabolized into smaller molecules by the gut microbiota. The pH values continuously decrease during fermentation, whereas, the amount of short-chain fatty acids steadily increase. Furthermore, CZIP-S3 could modulate the composition of gut microbiota, via lowering the ratio of Firmicutes/Bacteroidetes and increasing the relative abundance of Bacteroides, Bifidobacterium and Akkermansia. The data suggested that CZIP-S3 could potentially be used as an ingredient for functional foods or prebiotics to improve human health by promoting the relative abundances of beneficial bacteria.

Clinical outcomes of radioactive seed brachytherapy and microwave ablation in inoperable stage I non-small cell lung cancer.

This study assessed the efficacy and safety of radioactive iodine-125 seed ablation brachytherapy (RSABT) in comparison to microwave ablation therapy (MWAT) for treating inoperable stage I non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of data from stage I NSCLC patients who underwent CT-guided RSABT or MWAT. The primary outcomes measured were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. Of the patients included in the study, 71 underwent RSABT and 105 received MWAT. The median follow-up time for these groups was 47.4 months and 60 months, respectively. The PFS rates at 1-year, 3-year, and 5-year for the RSABT group were 87.3%, 72.6%, and 65.8%, while for the MWAT group, they were 89.5%, 69.3%, and 43.7%, respectively (P = 0.011). The OS rates at 1-year, 3-year, and 5-year for the RSABT group were 97.2%, 78.1%, and 66.1%, and for the MWAT group, they were 99%, 75.8%, and 55%, respectively (P = 0.112). Upon multivariate analysis, the treatment modality was identified as an independent predictor of PFS (P = 0.008). Additionally, both sex and T stage were found to be independent predictors of both PFS and OS (P < 0.05). Adverse events, such as pneumothorax, occurred in 50% of the MWAT group and 39% of the RSABT group (P = 0.313). The incidence of pleural effusion was 44% in the MWAT group compared to 14% in the RSABT group (P < 0.001). Needle bleeding was observed in 32% of the RSABT group and 5% of the MWAT group (P < 0.001). We conclude RSABT demonstrates promising efficacy and safety in the treatment of stage I NSCLC. However, further studies are essential to validate these preliminary findings.

Angiopoietin-like protein 3 deficiency combined with valsartan administration protects better against podocyte damage in streptozotocin-induced diabetic nephropathy mice.

Diabetic nephropathy (DN) is a common leading cause of end-stage renal disease (ESRD). Podocyte injury is a major pathogenesis of DN. Pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) is insufficient to fully prevent the development of ESRD. The present investigation aims to evaluate the protective function of valsartan, an angiotensin receptor blocker, alone and in combination with angiopoietin-like protein 3 (Angptl3) knockout against renal damage and podocyte injury in streptozotocin (STZ)-induced diabetic mice. The mice were divided into four groups: normal control group, STZ-induced DN group, valsartan + DN group (val, 100 mg/kg, po), and Angptl3-/- + valsartan + DN group. Tests on kidney function, renal pathology, podocyte ultrastructure, podocyte apoptosis, reactive oxygen species (ROS) production, and autophagy were performed. The combined Angptl3 knockout/valsartan treatment significantly attenuated diabetes-induced renal pathological damage and improved podocyte ultrastructure compared with valsartan alone. The combined administration ameliorated glomerular injury by increasing nephrin, podocin, and CD2-associated protein (CD2AP) expression levels and inhibiting podocyte loss by apoptosis. Compared with valsartan alone, Angptl3-/- and valsartan combination therapy significantly improved the renal function, as demonstrated by decreasing levels of serum urea nitrogen, creatinine, and urinary albumin. Additionally, the combination treatment significantly activated autophagy and reduced the ROS production than valsartan alone. These findings highlight the role of valsartan to Angptl3 knockout could have much better outcome that opens the future for drugs that could inhibit Angptl3.

[Analysis of clinical characteristics and genetic variants in a child with Isolated sulfite oxidase deficiency].

OBJECTIVE: To explore the genetic basis for a child with Isolated sulfite oxidase deficiency (ISOD). METHODS: The child and her parents were subjected to targeted capture and next-generation sequencing. Pathogenicity of candidate variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child was found to harbor compound heterozygous variants of the SUOX gene, namely c.1200C>G (p.Tyr400*) and c.1406_1421delCCTGGCAGGTGGCTAA (p.Thr469Serfs*20), which were inherited from her mother and father, respectively. The c.1200C>G was a known pathogenic variant, while the c.1406_1421delCCTGGCAGGTGGCTAA was unreported previously and predicted to be a pathogenic variant (PVS1+PM2_Supporting +PM3) based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The compound c.1200C>G and c.1406_1421delCCTGGCAGGTGGCTAA variants of the SUOX gene probably underlay the pathogenesis of ISOD in this child. Above finding has expanded the spectrum of SUOX gene variants and provided molecular evidence for the clinical diagnosis and genetic counseling for this pedigree.