CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Altruistic seagull optimization algorithm enables selection of radiomic features for predicting benign and malignant pulmonary nodules.

Accurately differentiating indeterminate pulmonary nodules remains a significant challenge in clinical practice. This challenge becomes increasingly formidable when dealing with the vast radiomic features obtained from low-dose computed tomography, a lung cancer screening technique being rolling out in many areas of the world. Consequently, this study proposed the Altruistic Seagull Optimization Algorithm (AltSOA) for the selection of radiomic features in predicting the malignancy risk of pulmonary nodules. This innovative approach incorporated altruism into the traditional seagull optimization algorithm to seek a global optimal solution. A multi-objective fitness function was designed for training the pulmonary nodule prediction model, aiming to use fewer radiomic features while ensuring prediction performance. Among global radiomic features, the AltSOA identified 11 interested features, including the gray level co-occurrence matrix. This automatically selected panel of radiomic features enabled precise prediction (area under the curve = 0.8383 (95 % confidence interval 0.7862-0.8863)) of the malignancy risk of pulmonary nodules, surpassing the proficiency of radiologists. Furthermore, the interpretability, clinical utility, and generalizability of the pulmonary nodule prediction model were thoroughly discussed. All results consistently underscore the superiority of the AltSOA in predicting the malignancy risk of pulmonary nodules. And the proposed malignant risk prediction model for pulmonary nodules holds promise for enhancing existing lung cancer screening methods. The supporting source codes of this work can be found at: https://github.com/zzl2022/PBMPN.

Type II photoinitiators with collagen-based cyanine for cell encapsulation under green-red LED.

3D bioprinting with cell-laden materials is an emerging technique for fabricating functional tissue constructs. However, current cell-laden bioinks often lack sufficient cytocompatibility with commonly used UV-light sources. In this study, green to red photoinduced hydrogel crosslinking was obtained by introducing synthesized biosafety photoinitiators and used in light-based direct ink writing (DIW) 3D printing for enabling cell encapsulation successfully. The novel type II photointiators contain iodonium (ONI) and synthesized cyanine dyes CZBIN, TDPABIN, Col-SH-CZ, and Col-SH-TD with strong absorption in the range of 400-600 nm. Collagen-based macromolecule dyes Col-SH-CZ and Col-SH-TD showed excellent cytocompatibility. The photochemistry of these photoinitiators revealed an efficient photoinduced electron transfer (PET) process from the singlet excited states of the dyes to iodonium (ONI), facilitating the crosslinking of the biogels. L929 cells were encapsulated in Gel-MA hydrogels containing various photoinitiating systems and exposed to near-ultraviolet, green, or red LED irradiation. DIW-type 3D printing of Gel-MA bioink with L929 cells was also evaluated. The cell viability achieved with green light encapsulation reached 90 %. This novel approach offers promising prospects for bioprinting functional tissues with enhanced cytocompatibility under visible light conditions.

Salivary-secreted vitellogenin suppresses H2O2 burst of plants facilitating Recilia dorsalis leafhopper feeding.

BACKGROUND: Vitellogenin (Vg), known as the yolk protein precursor for oocyte development in female insects, can be secreted to plant host from salivary glands of hemipterans, including rice leafhopper Recilia dorsalis. The aim of this study was to investigate the function of salivary-secreted Vg of R. dorsalis (RdVg) in rice host. We propose that RdVg possibly regulates the rice defense against insects, benefiting R. dorsalis feeding. RESULTS: RdVg was released into rice phloem along with saliva during R. dorsalis feeding. Knocking down RdVg increased the level of H2O2 and improved H2O2 metabolism in rice plants, making it difficult for R. dorsalis to feed. The transient expression or overexpression of the lipoprotein N-terminal domain of RdVg (RdVg2) significantly reduced hydrogen peroxide (H2O2) metabolism in plants. This suggests that salivary-secreted RdVg acts as an effector suppressing the H2O2 burst in rice plants, and RdVg2 is the key domain. RdVg2 could interact with rice sulfite oxidase (OsSO), which catalyzes the oxidation of SO3 2- and produces H2O2. Exposure of rice plants to R. dorsalis, overexpression of RdVg2 or knocking out OsSO reduced OsSO accumulation and SO3 2- oxidation, benefiting R. dorsalis feeding. However overexpression of OsSO increased SO3 2- oxidation and H2O2 metabolism, inhibiting R. dorsalis feeding. CONCLUSION: RdVg inhibits H2O2 generation via suppressing OsSO accumulation, ultimately benefiting R. dorsalis feeding. These findings identify RdVg as an effector that suppresses plant defense to insects, and provide insights into the function of salivary-secreted Vg in other Hemiptera insects. © 2024 Society of Chemical Industry.

Effects of Nudge Strategy-Based Dietary Education Intervention in Patients with Type 2 Diabetes Mellitus: A Cluster Randomized Controlled Trial.

OBJECTIVES: We aimed to assess the clinical effects of dietary education intervention utilizing the nudge strategy in individuals with type 2 diabetes mellitus (T2DM). BACKGROUND: The global prevalence of T2DM and its associated complications presents a significant health challenge. While the benefits of dietary education intervention for blood glucose management are widely acknowledged, patients often struggle to adhere to dietary recommendations. The implementation of the nudge strategy may offer a promising solution to change unhealthy dietary behavior and enhance diabetes control among individuals with T2DM. METHODS: This is a sub-study within a broader cluster-randomized trial that evaluated the effects of nudge-based dietary education and traditional dietary education intervention. Measurements of HbA1c, fasting blood glucose (FBG), body mass index (BMI), blood lipid levels, blood pressure, dietary behavior, and diabetes distress were assessed at baseline and 3 months after the intervention in 147 individuals with T2DM from six primary care practices in Beijing, China. RESULTS: All outcome measurements were complete at two time points for 134 participants. Results showed that compared to the control group, the intervention group achieved a significantly greater reduction in HbA1c, FBG, BMI, total cholesterol, low-density lipoprotein cholesterol, blood pressure, total energy intake, carbohydrate intake, fat intake, and protein intake and had lower diabetes distress. The intervention group also maintained HDL-C levels and had a significantly greater increase in vegetable intake, while changes in triglycerides were similar in the two groups . CONCLUSION: The present study provides evidence that nudge strategy-based dietary education intervention is effective in improving blood glucose, BMI, blood lipid levels, and blood pressure and facilitating changes in patients' dietary behavior and diabetes distress. These findings suggest that implementing nudge strategies can contribute to the optimization of T2DM dietary management and overall patient well-being.

An Endocellulase-Triggered NO Targeted-Release Enzyme-Prodrug Therapy System and Its Application in Ischemia Injury.

Nitric oxide (NO) is a crucial gaseous signaling molecules in regulating cardiovascular, immune, and nervous systems. Controlled and targeted NO delivery is imperative for treating cancer, inflammation, and cardiovascular diseases. Despite various enzyme-prodrug therapy (EPT) systems facilitating controlled NO release, their clinical utility is hindered by nonspecific NO release and undesired metabolic consequence. In this study, a novel EPT system is presented utilizing a cellobioside-diazeniumdiolate (Cel2-NO) prodrug, activated by an endocellulase (Cel5A-h38) derived from the rumen uncultured bacterium of Hu sheep. This system demonstrates nearly complete orthogonality, wherein Cel2-NO prodrug maintains excellent stability under endogenous enzymes. Importantly, Cel5A-h38 efficiently processes the prodrug without recognizing endogenous glycosides. The targeted drug release capability of the system is vividly illustrated through an in vivo near-infrared imaging assay. The precise NO release by this EPT system exhibits significant therapeutic potential in a mouse hindlimb ischemia model, showcasing reductions in ischemic damage, ambulatory impairment, and modulation of inflammatory responses. Concurrently, the system enhances tissue repair and promotes function recovery efficacy. The novel EPT system holds broad applicability for the controlled and targeted delivery of essential drug molecules, providing a potent tool for treating cardiovascular diseases, tumors, and inflammation-related disorders.

Enhancement of non-covalent interaction between soy protein isolate and quercetin by sodium alginate.

Effects of sodium alginate (SA) on the non-covalent interaction between soybean protein isolate (SPI) and quercetin (Que) were investigated by multispectral technology, molecular docking and dynamics simulation technology. Structural alterations of the binary complexes were observed after SA addition, characterized by a red shift of maximum fluorescence emission wavelength. The introduction of 0.1% (w/v) SA led to a reduction of 12.3% in the α-helix and ß-sheet structures, accompanied by 12.6% increase in the ß-turn and random coil conformations. The binding of SA to SPI provided electrostatic interactions and facilitated the subsequent binding of SPI to Que. Molecular docking confirmed that hydrophobic interactions and electrostatic interactions were also the main driving force. Molecular dynamics simulation emphasized that the ternary complexes with SA exhibited greater stability compared to the binary ones. The foaming and emulsifying properties of SPI-Que complexes were enhanced by 33.76% and 68.28%, respectively, due to the addition of SA.

(-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescence in vitro and prevents skin aging in vivo by reducing SASP.

Objectives: To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence ß-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL-6, IL-8, IL-1ß, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. Results: (-)-α-Bis reduced the expression of senescence-associated ß-galactosidase (SA-ß-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-ß-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo.

A comparative study on cadmium tolerance and applicability of two Solanum lycopersicum L. cultivars.

Solanum lycopersicum L. can be classified into low Cd-accumulating and high Cd-accumulating types based on their accumulation characteristics of cadmium (Cd). There are many common S. lycopersicum varieties available in the market, but their specific Cd tolerance and enrichment abilities are not well understood. This article uses two S. lycopersicum cultivars, Yellow Cherry and Yellow Pearl, as experimental materials. The experimental method of soil pot planting was adopted, and Cd concentrations in the soil were added at 0, 0.6, 1.5, 2.5, 5, and 10 mg/kg. The changes in Cd content, biomass, photosynthetic pigment content, and photosynthetic parameters of the two S. lycopersicum cultivars were analyzed to screen for low-accumulation S. lycopersicum cultivars. The results showed that S. lycopersicum are Cd-sensitive plants. The Cd accumulation, photosynthetic parameters, and other basic indicators of Yellow Cherry basically showed significant differences when the soil Cd concentration was 0.6 mg/kg, and the biomass showed significant differences when the soil Cd concentration was 1.5 mg/kg. Except for the Cd accumulation in the roots and leaves of Yellow Pearl, which showed significant differences at a soil Cd concentration of 0.6 mg/kg, the other indicators basically showed significant differences when the soil Cd concentration was 1.5 mg/kg. When the soil Cd concentration was 0.6 mg/kg, the Cd accumulation in the fruit of Yellow Pearl was 0.04 mg/kg, making it a low-accumulation S. lycopersicum variety suitable for promoting cultivation in Cd-contaminated soil at 0.6 mg/kg. In conclusion, the Cd accumulation in the fruit of Yellow Pearl is significantly lower than that of Yellow Cherry and even below the Cd limit value for fresh vegetables specified in GB2762-2017. Therefore, Yellow Pearl can be grown as edible crops in soils with Cd concentrations ≤0.6 mg/kg. Furthermore, Yellow Cherry demonstrate strong Cd tolerance and can be used for the remediation of Cd-contaminated soils.

Enhanced Optoelectronic Performance of p-WSe2/Re0.12W0.42Mo0.46S2 Heterojunction.

Stacking of van der Waals (vdW) heterostructures and chemical element doping have emerged as crucial methods for enhancing the performance of semiconductors. This study proposes a novel strategy for modifying heterostructures by codoping MoS2 with two elements, Re and W, resulting in the construction of a RexWyMo1-x-yS2/WSe2 heterostructure for the preparation of photodetectors. This approach incorporates multiple strategies to enhance the performance, including hybrid stacking of materials, type-II band alignment, and regulation of element doping. As a result, the RexWyMo1-x-yS2/WSe2 devices demonstrate exceptional performance, including high photoresponsivity (1550.22 A/W), high detectivity (8.17 × 1013 Jones), and fast response speed (rise/fall time, 190 ms/1.42 s). Moreover, the ability to tune the band gap through element doping enables spectral response in the ultraviolet (UV), visible light, and near-infrared (NIR) regions. This heterostructure fabrication scheme highlights the high sensitivity and potential applications of vdW heterostructure (vdWH) in optoelectronic devices.

Telomere-to-telomere reference genome for Panax ginseng highlights the evolution of saponin biosynthesis.

Ginseng (Panax ginseng) is a representative of Chinese traditional medicine, also used worldwide, while the triterpene saponin ginsenoside is the most important effective compound within it. Ginseng is an allotetraploid, with complex genetic background, making the study of its metabolic evolution challenging. In this study, we assembled a telomere-to-telomere ginseng reference genome, constructed of 3.45 Gb with 24 chromosomes and 77 266 protein-coding genes. Additionally, the reference genome was divided into two subgenomes, designated as subgenome A and B. Subgenome A contains a larger number of genes, whereas subgenome B has a general expression advantage, suggesting that ginseng subgenomes experienced asymmetric gene loss with biased gene expression. The two subgenomes separated approximately 6.07 million years ago, and subgenome B shows the closest relation to Panax vietnamensis var. fuscidiscus. Comparative genomics revealed an expansion of gene families associated with ginsenoside biosynthesis in both ginseng subgenomes. Furthermore, both tandem duplications and proximal duplications play crucial roles in ginsenoside biosynthesis. We also screened functional genes identified in previous research and found that some of these genes located in colinear regions between subgenomes have divergence functions, revealing an unbalanced evolution in both subgenomes and the saponin biosynthesis pathway in ginseng. Our work provides important resources for future genetic studies and breeding programs of ginseng, as well as the biosynthesis of ginsenosides.

Tunable metasurfaces for implementing terahertz controllable NOT logic gate functions.

Compared with traditional electrical logic gates, optical or terahertz (THz) computing logic gates have faster computing speeds and lower power consumption, and can better meet the huge data computing needs. However, there are limitations inherent in existing optical logic gates, such as single input/output channels and susceptibility to interference. Here, we proposed a new approach utilizing polarization-sensitive graphene-vanadium dioxide metasurface THz logic gates. Benefitting from two actively tunable materials, the proposed controlled-NOT logic gate(CNOT LG) enables versatile functionality through a dual-parameter control system. This system allows for the realization of multiple output states under diverse polarized illuminating conditions, aligning with the expected input-output logic relationship of the CNOT LG. Furthermore, to demonstrate the robustness of the designed THz CNOT LG metasurface, we designed an imaging array harnessing the dynamic control capabilities of tunable meta-atoms, facilitating clear near-field imaging. This research is promising for advancing CNOT LG applications in the THz spectrum. It has potential applications in telecommunications, sensing, and imaging.

Salidroside modulates repolarization through stimulating Kv2.1 in rats.

BACKGROUND: Voltage-gated potassium (Kv) channel growth is strongly associated with the development of arrhythmia. Salidroside (Sal), an active component from Rhodiola crenulata, has been shown to exert protective effects against heart disease. The present study was conducted to investigate the effects of Sal on Kv2.1 channel, and to explore the ionic mechanism of anti-arrhythmic. METHODS: In this study, we utilized cisapride (Cis., A stimulant that prolongs the QT interval and causes cardiac arrhythmias) by intravenous injection to establish an arrhythmia model, and detected the effects of Sal on electrocardiography (ECG) and pressure volume loop (P-V loop) in SD rats. The effect of Sal on ECG of citalopram (Cit., a Kv2 channel inhibition)-evoked arrhythmia rat models was further evaluated by monitoring the dynamic changes of multiple indicators of ECG. Then, we detected the effect of Sal on the viability of hypoxic H9c2 cells using CCK-8 assay. After that, the effect of Sal on Kv channel currents (IKv) and Kv2.1 channel currents (IKv2.1) in H9c2 cells under normal and hypoxic conditions was examined using whole-cell patch clamp technique. In addition, the effect of Sal on IKv and IKv2.1 in H9c2 cells was determined under the inhibition of Kv and Kv2.1 channels. HEK293 cells stably transfected with Kv2.1 plasmids were also used to investigate the IKv2.1 changes under Sal pre-treated and co-incubated conditions. In addition, potential interactions of Sal with Kv2.1 protein were predicted and tested by molecular docking, molecular dynamics simulation (MDS), localized surface plasmon resonance (LSPR), and cellular thermal shift assay (CETSA) techniques, respectively. Furthermore, gene and protein levels of Kv2.1 in Sal-treated H9c2 cell were estimated by qRT-PCR, Western blot (WB) and immunofluorescence (IF) analysis. RESULTS: Sal shortened the prolongated QT interval and ameliorated the cardiac impairment associated with arrhythmia in SD rats caused by Cis., as reflected in the ECG and P-V loop data. And Sal was also protective against arrhythmia in rats caused by Kv2 channel inhibition. At the cellular level, Sal increased cell viability after CoCl2-induced hypoxic injury in H9c2 cells. Whole-cell patch clamp assay confirmed that Sal inhibited both IKv and IKv2.1 in normal H9c2 cells, while enhanced IKv and IKv2.1 in cardiomyocytes after hypoxic injury. And Sal enhanced IKv inhibited by 1.5 mM 4-AP and upregulated all inhibition of Kv2 channels induced by 20 mM 4-AP administration, antagonized the IKv2.1 inhibitory effect of Cit. Moreover, Sal pre-administration for 24 h and immediate administration increased IKv2.1 in HEK293 cells stably transfected with Kv2.1 plasmids. Molecular docking demonstrated the potential binding of Sal to the Kv2.1 protein, with calculated binding energy of -5.4 kcal/mol. MDS test illustrated that the average hydrogen bonding of the Sal-Kv2.1 complexes was 30.89%. LSPR results verified the potential binding of Sal to Kv2.1 protein with an affinity value of 9.95 × 10-4 M. CETSA assay confirmed Sal can enhance the expression of Kv2.1 protein in H9c2 cells treated with heat, which suggests that Sal may bind to Kv2.1 protein. The results of WB, qRT-PCR, and IF further argued that Sal pre-administration for 24 h enhanced the levels of the Kv2.1 gene and protein (with no effects on the Kv2.1 gene and protein for H9c2 cells co-incubated with Sal for 6 h and 12 h). CONCLUSION: Overall, our findings indicate that Sal can resist drug-induced arrhythmias in SD rats, partially by modulating repolarization through stimulating Kv2.1.

Causal associations between psoriasis, eczema, urticaria, and mental illness: A bidirectional Mendelian randomization study of the European population.

Observational studies have reported a relationship between multiple common dermatoses and mental illness. To assess the potential bidirectional causality between 3 skin disorders (psoriasis, eczema, and urticaria) and 4 psychiatric disorders (bipolar disorder, schizophrenia, major depressive disorder, and anxiety) in the European population, we used Mendelian randomization (MR) analysis, which provides definitive evidence for causal inference. Eligible single nucleotide polymorphisms were screened for dermatological and psychiatric disorders using a genome-wide association study database. We conducted bidirectional, 2-sample MR analysis using instrumental variables related to psoriasis, eczema, and urticaria as exposure factors, and bipolar disorder, schizophrenia, major depression, and anxiety as outcomes. Reverse MR analysis with bipolar disorder, schizophrenia, major depression, and anxiety as exposure and psoriasis, eczema, and urticaria as outcomes were also performed, and the causality was analyzed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. To thoroughly assess causality, sensitivity analyses were conducted using the IVW, MR-PRESSO, and MR-Egger methods. The results showed that bipolar disorder increased the incidence of psoriasis (odds ratio = 1.271, 95% confidence interval = 1.003-1.612, P = .047), heterogeneity test with Cochran Q test in the IVW showed P value > .05, (P = .302), the MR-Pleiotropy and MR-PRESSO (outlier methods) in the multiplicity test showed P value > .05, (P = .694; P = .441), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.060; SE = 0.139; P = .694). Major depression increased the risk of eczema (odds ratio = 1.002, 95% confidence interval = 1.000-1.004, P = .024), heterogeneity test showed P value > .05, (P = .328), multiplicity detection showed P value > .05, (P = .572; P = .340), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.099; SE = 0.162; P = .572). Sensitivity analyses of the above results were reliable, and no heterogeneity or multiplicity was found. This study demonstrated a statistically significant causality between bipolar disorder and psoriasis, major depression, and eczema in a European population, which could provide important information for physicians in the clinical management of common skin conditions.

Obstructive Sleep Apnea Syndrome and Obesity Indicators, Circulating Blood Lipid Levels, and Adipokines Levels: A Bidirectional Two-Sample Mendelian Randomization Study.

Purpose: This investigation sought to elucidate the genetic underpinnings that connect obesity indicators, circulating blood lipid levels, adipokines levels and obstructive sleep apnea syndrome (OSAS), employing a bidirectional two-sample Mendelian randomization (MR) analysis that utilizes data derived from extensive genome-wide association studies (GWAS). Methods: We harnessed genetic datasets of OSAS available from the FinnGen consortium and summary data of four obesity indices (including neck circumference), seven blood lipid (including triglycerides) and eleven adipokines (including leptin) from the IEU OpenGWAS database. We primarily utilized inverse variance weighted (IVW), weighted median, and MR-Egger methods, alongside MR-PRESSO and Cochran's Q tests, to validate and assess the diversity and heterogeneity of our findings. Results: After applying the Bonferroni correction, we identified significant correlations between OSAS and increased neck circumference (Odds Ratio [OR]: 3.472, 95% Confidence Interval [CI]: 1.954-6.169, P= 2.201E-05) and decreased high-density lipoprotein (HDL) cholesterol levels (OR: 0.904, 95% CI: 0.858-0.952, P= 1.251E-04). Concurrently, OSAS was linked to lower leptin levels (OR: 1.355, 95% CI: 1.069-1.718, P= 0.012) and leptin receptor levels (OR: 0.722, 95% CI: 0.530-0.996, P= 0.047). Sensitivity analyses revealed heterogeneity in HDL cholesterol and leptin indicators, but further multiplicative random effects IVW method analysis confirmed these correlations as significant (P< 0.05) without notable heterogeneity or horizontal pleiotropy in other instrumental variables. Conclusion: This investigation compellingly supports the hypothesis that OSAS could be a genetic predisposition for elevated neck circumference, dyslipidemia, and adipokine imbalance. These findings unveil potential genetic interactions between OSAS and metabolic syndrome, providing new pathways for research in this domain. Future investigations should aim to delineate the specific biological pathways by which OSAS impacts metabolic syndrome. Understanding these mechanisms is critical for developing targeted prevention and therapeutic strategies.

The role of ultraviolet radiation in the flavor formation during drying processing of Pacific saury (Cololabis saira).

BACKGROUND: Traditional sun-drying aquatic products are popular and recognized by customers, owing to their unique flavor and long-term preservation. However, the product quality and production efficiency cannot be guaranteed. Cololabis saira is rich in unsaturated fatty acids, which are susceptible to hyperoxidation during the drying process. This study aimed to make clear the role of ultraviolet (UV) radiation in flavor formation during drying processes of Cololabis saira to develop a modern drying technology. RESULTS: Lipid oxidation analysis revealed that moderate hydrolytic oxidation occurred in the UV-assisted cold-air drying group due to the combined influence of UV and cold-air circulation, resulting in the thiobarbituric acid reactive substances value being higher than that of cold-air drying group but lower than the natural drying group. Hexanal, heptanal, cis-4-heptenal, octanal, nonanal, (trans,trans)-2,4-heptadienal, (trans,trans)-2,6-nonanedial, 1-octen-3-ol, heptanol, 2,3-pentanedione, 3,5-octadien-2-one and trimethylamine were identified as the characteristic flavor odor-active compounds present in all Cololabis saira samples. Yet, during the natural drying process, sunlight promoted the lipid oxidation, resulting in the highest degree of lipid oxidation among three drying methods. Light and heat promoted lipid oxidation in Cololabis saira prepared through natural drying process, leading to a large accumulation of volatile compounds, such as 3-methylbutyraldehyde, 2,3-pentanedione, 1-propanol, and 3-pentanone. Cold air circulation inhibited lipid oxidation to some extent, resulting in a blander flavor profile. More cis-4-heptenal, cis-2-heptenal, octanal and 2-ethylfuran accumulated during the UV-assisted cold-air drying process, enriching its greasy flavor and burnt flavor. CONCLUSION: UV-assisted cold-air drying could promote moderate lipid oxidation, which is beneficial for improving product flavor. To sum up, UV radiation played a crucial role in the flavor formation during the drying process of Cololabis saira. © 2024 Society of Chemical Industry.

Intelligent bell facial paralysis assessment: a facial recognition model using improved SSD network.

With the continuous progress of technology, the subject of life science plays an increasingly important role, among which the application of artificial intelligence in the medical field has attracted more and more attention. Bell facial palsy, a neurological ailment characterized by facial muscle weakness or paralysis, exerts a profound impact on patients' facial expressions and masticatory abilities, thereby inflicting considerable distress upon their overall quality of life and mental well-being. In this study, we designed a facial attribute recognition model specifically for individuals with Bell's facial palsy. The model utilizes an enhanced SSD network and scientific computing to perform a graded assessment of the patients' condition. By replacing the VGG network with a more efficient backbone, we improved the model's accuracy and significantly reduced its computational burden. The results show that the improved SSD network has an average precision of 87.9% in the classification of light, middle and severe facial palsy, and effectively performs the classification of patients with facial palsy, where scientific calculations also increase the precision of the classification. This is also one of the most significant contributions of this article, which provides intelligent means and objective data for future research on intelligent diagnosis and treatment as well as progressive rehabilitation.

Discovery and preclinical evaluation of KYS202004A, a novel bispecific fusion protein targeting TNF-α and IL-17A, in autoimmune disease models.

The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2  mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.

A comprehensive study of the colloidal properties, biocompatibility, and synergistic antioxidant actions of Antarctic krill phospholipids.

Excipient selection is crucial to address the oxidation and solubility challenges of bioactive substances, impacting their safety and efficacy. AKPL, a novel ω-3 polyunsaturated fatty acids (PUFAs) esterified phospholipid derived from Antarctic krill, demonstrates unique antioxidant capabilities and synergistic effects. It exhibits pronounced surface activity and electronegativity at physiological pH, as evidenced by a critical micelle concentration (CMC) of 0.15 g/L and ζ-potential of -49.9 mV. In aqueous environments, AKPL self-assembles into liposomal structures, offering high biocompatibility and promoting cell proliferation. Its polyunsaturated bond-rich structure provides additional oxidation sites, imparting antioxidant properties superior to other phospholipids like DSPC and DOPC. Additionally, AKPL augments the efficacy of lipophilic antioxidants, such as alpha-tocopherol and curcumin, in aqueous media through both intermolecular and intramolecular interactions. In sum, AKPL emerges as an innovative unsaturated phospholipid, offering new strategies for encapsulating and delivering oxygen-sensitive agents.

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

Background: The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. Methods: In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. Results: In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). Conclusions: The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.