Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Integrated simulation-surrogate-optimization modeling framework for multiple tradeoffs among socioeconomic and ecological targets in reservoir operations.

Integrated reservoir water quantity and quality management is significant for water supply security and river ecosystem health. However, the spatiotemporal heterogeneity of water quality and the nonuniform response of multiple indicators to operation changes make it difficult to determine optimal operation schedules. This study proposes a coupled simulation-surrogate-optimization modeling approach for compromising multiple water quantity and quality targets in reservoir operations. The Environmental Fluid Dynamics Code (EFDC) was used to simulate spatiotemporal reservoir water quality dynamics. Subsequently, an ecological damage assessment method was established, accounting for the spatiotemporal heterogeneity of multiple water quality indicators and the nonlinear relationship between the water quality deterioration and ecological damage. To quickly simulate the ecological damage, a surrogate model was developed using the nonlinear autoregressive network with exogenous inputs (NARX). Finally, the surrogate model was integrated into a reservoir operation optimization model for compromising socioeconomic and ecological targets. By applying the methods to China's Danjiangkou Reservoir as a case, it was shown that more even nutrient distribution in the reservoir increased water eutrophication area while reducing concentration peak values, which helped decrease the ecological damage. Operation changes could lead to opposite effects on in-reservoir and downstream ecological targets, increasing operation optimization complexity. Both ecological and socioeconomic benefits significantly increased (by 9.4%-16.4%) during dry years under the optimized operation scheme, implying that synergies were obtained. This study offers implications and a management tool for reservoir operations to address the multiple tradeoffs among socioeconomic and ecological benefits.

Electroacupuncture improves cognitive impairment after ischemic stroke based on regulation of mitochondrial dynamics through SIRT1/PGC-1α pathway.

In recent years, the mechanism of acupuncture in the treatment of post-stroke cognitive impairment (PSCI) has not been fully elucidated. The balance between mitochondrial fission and fusion is important for PSCI. Our previous research demonstrated that electroacupuncture can improve learning and memory in middle cerebral artery ischemia reperfusion (MCAO/R) rats. However, the specific mechanism by which electroacupuncture improves learning and memory in MCAO/R rats by regulating mitochondrial fission and fusion needs to be further investigated. The MCAO/R rats was developed using the line-bolt method. The rats were randomly divided into sham-operated (Sham), model (MCAO/R), electroacupuncture (MCAO/R + EA) and sham-electroacupuncture (MCAO/R + sham EA) groups. Investigating the effects of EA on the expression of Sirtuin1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Optic atrophy 1R + (OPA1) and Dynamin-related protein 1 (DRP1) in hippocampal neurons and on the morphology and function of hippocampal neurons and mitochondria. EA was able to reduce neurologic deficit scores and cerebral infarct volume and improve new object discrimination in MCAO/R rats, but there were no significant changes in these indices in the sham-electroacupuncture group. Moreover, EA increased the expression of SIRT1, PGC-1α, and OPA1 in hippocampal tissues, inhibited the expression of DRP1, attenuated neuronal and mitochondrial damage, and reduced mitochondrial fragmentation. The mechanism by which EA improves learning memory deficits in MCAO/R rats may be related to the inhibition of SIRT1/PGC-1α expression, the enhancement of mitochondrial fusion and the obstruction of its fission, and the reduction of hippocampal neuronal damage.

Global burden of osteoarthritis: Prevalence and temporal trends from 1990 to 2019.

OBJECTIVE: To investigate the age-standardized prevalence rate (ASPR) and temporal trends for hip, knee, hand, and other osteoarthritis (OA) at a global, continental, and national level. DESIGN: The estimates and 95% uncertainty intervals (UIs) for case number and ASPR of OA were derived from the Global Burden of Diseases Study (GBD) 2019. The joinpoint regression analysis was utilized to examine the temporal trends from 1990 to 2019. RESULTS: In 2019, the global ASPR of hip, knee, hand, and other OA was 400.95 (95% UI: 312.77-499.41), 4375.95 (95% UI: 3793.04-5004.9), 1726.38 (95% UI: 1319.91-2254.85), and 745.62 (95% UI: 570.16-939.8). As for the ASPR of hip OA, hand OA, and other OA, Europe and America had higher rates than Asia and Africa, and Asia was second only to America in knee OA ASPRs. The period 1990-2019, the ASPR at global level dropped significantly for hand OA (AAPC = -0.4%, 95% CI: -0.47 to -0.34) and increased significantly for hip OA (AAPC = 0.43%, 95% CI: 0.39-0.46), knee OA (AAPC = 0.17%, 95% CI: 0.09-0.24) and other OA (AAPC = 0.16%, 95% CI: 0.15-0.17). Different continents, countries, and periods demonstrated significant changes. CONCLUSIONS: Globally, America has the highest OA burden and Asia has a higher knee OA burden. Appropriate prevention and control measures to reduce modifiable risk factors are needed to reduce the burden of OA.

Enhanced Hydrogen Production via Photothermal-Coupled Ultrasound Pyrolysis of Waste Bio-Oil.

The creation of hydrogen using the lower-cost feedstock, waste organics (WOs), e.g. kitchen waste bio-oil, is a win-win solution, because it can both solve energy problems and reduce environmental pollution. Ultrasound has received considerable interest in organic decomposition; however, the application of ultrasound alone is not a good choice for the hydrogen production from WOs, because of the energy consumption and efficiency. To boost the hydrogen production based on ultrasonic cavitation cracking of bio-oil, photothermal materials are introduced into the hydrogen production system to form localized hot spots. Materials carbon black (CB), carbon nanotubes (CNT), and silicon dioxide (SiO2) all exhibit significant enhancing effects on the hydrogen production from bio-oil, and the CB exhibits the most significant strengthening effect among these materials. When the dosage of CB is 5 mg, hydrogen production rate is 180.1 µmol · h-1, representing a notable 1.7-fold increase compared to the production rate without CB. In the presence of light and ultrasound, the hydrogen production rate can be increased by 66.7-fold compared to the situation where only light is present without ultrasound.

A pair of nuclear factor Y transcription factors act as positive regulators in jasmonate signaling and disease resistance in Arabidopsis.

The plant hormone jasmonate (JA) regulates plant growth and immunity by orchestrating a genome-wide transcriptional reprogramming. In the resting stage, JASMONATE-ZIM DOMAIN (JAZ) proteins act as main repressors to regulate the expression of JA-responsive genes in the JA signaling pathway. However, the mechanisms underlying de-repression of JA-responsive genes in response to JA treatment remain elusive. Here, we report two nuclear factor Y transcription factors NF-YB2 and NF-YB3 (thereafter YB2 and YB3) play key roles in such de-repression in Arabidopsis. YB2 and YB3 function redundantly and positively regulate plant resistance against the necrotrophic pathogen Botrytis cinerea, which are specially required for transcriptional activation of a set of JA-responsive genes following inoculation. Furthermore, YB2 and YB3 modulated their expression through direct occupancy and interaction with histone demethylase Ref6 to remove repressive histone modifications. Moreover, YB2 and YB3 physically interacted with JAZ repressors and negatively modulated their abundance, which in turn attenuated the inhibition of JAZ proteins on the transcription of JA-responsive genes, thereby activating JA response and promoting disease resistance. Overall, our study reveals the positive regulators of YB2 and YB3 in JA signaling by positively regulating transcription of JA-responsive genes and negatively modulating the abundance of JAZ proteins.

ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury.

In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5 mM) and high (25 mM) glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.

Shrimp hemocyanin elicits a potent humoral response in mammals and is favorable to hapten conjugation.

Conjugation to a carrier protein is essential to give rise to the antigenicity of hapten. Three carrier proteins e.g. KLH (Keyhole Limpet hemocyanin), BSA (bovine serum albumin), and OVA (Ovalbumin) were used mostly. KLH is advantageous to the others, majorly owing to its strong immunogenicity and limited usage in other biological assays. However, the cost of obtaining Keyhole Limpet is high and the solubility of KLH is not as well as the other carriers, especially after hapten conjugation. Here, we extracted the shrimp hemocyanin (SHC) from Litopenaeus vannamei (L. vannamei), which is a commonly sea product worldwide. The high pure SHC could be acquired by two-step purification, with a production yield of > 1 g proteins (98% pure) per 1 kg shrimp. Compared to KLH, the peptide-SHC conjugates exhibit higher solubility after hapten conjugation. Meanwhile, compared with KLH, SHC induces comparable antibody production efficiency in mammals, with or without conjugation. Furthermore, rabbit polyclonal antibodies or mouse monoclonal antibodies were generated by immunizing SHC-peptide conjugates, and the subsequent antibodies were confirmed to be used in western blot, immunofluorescence and immunohistochemistry. Therefore, we demonstrated that SHC may be used as a substitute for KLH in future antibody and vaccine development.

Distribution of EGFR fusions in 35,023 Chinese patients with solid tumors-the frequency, fusion partners and clinical outcome.

BACKGROUND: Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored. METHODS: Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). RESULTS: In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p < 0.0001) in the TCGA cohort, suggesting that EGFR fusion might be a high-risk factor for poor prognosis. CONCLUSIONS: Our study is the first retrospective analysis of EGFR fusions in a large-scale solid tumor population, which may provide a reference for future EGFR-TKI clinical trials with EGFR fusions.

Host Cells Upregulate Phosphate Transporter PIT1 to Inhibit Ehrlichia chaffeensis Intracellular Growth.

Ehrlichia chaffeensis infects and proliferates inside monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. After internalization, E. chaffeensis resides in specialized membrane-bound inclusions, E. chaffeensis-containing vesicles (ECVs), to evade from host cell innate immune responses and obtain nutrients. However, mechanisms exploited by host cells to inhibit E. chaffeensis growth in ECVs are still largely unknown. Here we demonstrate that host cells recognize E. chaffeensis Ech_1067, a penicillin-binding protein, and then upregulate the expression of PIT1, which is a phosphate transporter and transports phosphate from ECVs to the cytosol to inhibit bacterial growth. We found that host cells upregulate the PIT1 expression upon E. chaffeensis infection using transcriptome sequencing, qRT-PCR and Western blotting, and PIT1 is localized on the ECV membrane in infected THP-1 cells using confocal microscopy. Silence of PIT1 using shRNA enhances E. chaffeensis intracellular growth. Finally, we found that E. chaffeensis Ech_1067 induces the upregulation of PIT1 expression through the MyD88-NF-κB pathway using recombinant protein for stimulation and siRNA for silence. Our findings deepen the understanding of the innate immune responses of host cells to inhibit bacterial intracellular growth and facilitate the development of new therapeutics for HME.

Variations in the oxidation potential of PM2.5 in an old industrial city in China from 2015 to 2018.

PM2.5 pollution in China has decreased dramatically, but how its health effects change is not clear. There are 120 old industrial cities in China, where the sources, composition, and health effects of PM2.5 may be significantly different with other cities. Huangshi, an old industrial city in central China, underwent intense green transformations from 2015 to 2018. In this study, we collected ambient PM2.5 samples in 2015 and 2018 at an urban site in Huangshi. The average PM2.5 concentration decreased from 83.44 ± 48.04 µg/m3 in 2015 to 68.03 ± 39.41 µg/m3 in 2018. However, the average volume-normalized dithiothreitol (DTTv) of PM2.5 increased from 1.38 ± 0.45 nmol/min/m3 to 2.14 ± 1.31 nmol/min/m3 and the DTT normalized by particulate mass (DTTm) increased from 20.6 ± 10.1 pmol/min/µg to 40.07 ± 21.9 pmol/min/µg, indicating increased exposure risk and inherent toxicity. The increased toxicity of PM2.5 might be related to the increased trace elements (TEs) concentrations. The positive matrix factorization and multiple linear regression methods were employed to quantify the contributions of emission sources to PM2.5 and DTTv. The results showed that the contribution of coal combustion, industry, and dust to PM2.5 decreased significantly from 2015 to 2018, while that of vehicle emission and secondary sources increased. Despite the decreased fraction of coal combustion and industry sources, their contribution to DTTv increased slightly, which was caused by the increased intrinsic toxicity. The increased intrinsic toxicity was possibly caused by increased TEs, such as Pb, Cu, and V. Besides, the contribution of vehicle emission to DTTv also increased. Overall, these results provide valuable insights into the effectiveness of controlling strategies in reducing particulate health impacts in old industrial cities, and stress the necessity of formulating toxicity-oriented controlling strategies, with special attention to TEs from coal combustion and industry sources as well as vehicle emissions.

Research on the quantitative relationship of the viscosity reduction effect of large-ring cyclodextrin on potato starch during gelatinization process and mechanism analysis.

Starch is extensively used across various fields due to its renewable properties and cost-effectiveness. Nonetheless, the high viscosity that arises from gelatinization poses challenges in the industrial usage of starch at high concentrations. Thus, it's crucial to explore techniques to lower the viscosity during gelatinization. In this study, large-ring cyclodextrins (LR-CDs) were synthesized from potato starch (PS) by using 4-α-glucanotransferase and then added to PS to alleviate the increased viscosity during gelatinization. The results from rapid viscosity analyzer (RVA) demonstrated that the inclusion of 5 % (w/w) LR-CDs markedly reduced the peak viscosity (PV) and final viscosity (FV) of PS by 49.85 % and 28.17 %. In addition, there was a quantitative relationship between PV and LR-CDs. The equation was fitted as y = 2530.73×e-x/2.48+1832.79, which provided a basis for the regulation of PS viscosity. The mechanism of LR-CDs reducing the viscosity of PS was also studied. The results showed that the addition of LR-CDs inhibited the gelatinization of PS by enhancing orderliness and limiting water absorption, resulting in a decrease in viscosity. This study provides a novel method for reducing the viscosity of starch, which is helpful for increasing its concentration and reducing energy consumption in industrial applications.

Fairness in Classifying and Grouping Health Equity Information.

This paper explores the balance between fairness and performance in machine learning classification, predicting the likelihood of a patient receiving anti-microbial treatment using structured data in community nursing wound care electronic health records. The data includes two important predictors (gender and language) of the social determinants of health, which we used to evaluate the fairness of the classifiers. At the same time, the impact of various groupings of language codes on classifiers' performance and fairness is analyzed. Most common statistical learning-based classifiers are evaluated. The findings indicate that while K-Nearest Neighbors offers the best fairness metrics among different grouping settings, the performance of all classifiers is generally consistent across different language code groupings. Also, grouping more variables tends to improve the fairness metrics over all classifiers while maintaining their performance.

Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy.

Numerous studies have demonstrated that chronic stress during pregnancy (CSDP) can induce depression and hippocampal damage in offspring. It has also been observed that high levels of corticotropin-releasing hormone (CRH) can damage hippocampal neurons, and intraperitoneal injection of a corticotropin releasing hormone receptor 1 (CRHR1) antagonist decreases depression-like behavior and hippocampal neuronal damage in a mouse depression model. However, whether CSDP causes hippocampal damage and depression in offspring through the interaction of CRH and hippocampal CRHR1 remains unknown and warrants further investigation. Therefore, hippocampal Crhr1 conditional gene knockout mice and C57/BL6J mice were used to study these questions. Depression-related indexs in male offspring mice were examined using the forced swim test (FST), sucrose preference test (SPT), tail suspension test (TST) and open field test (OFT). Serum CRH levels were measured by enzyme-linked immunosorbent assay (ELISA). Golgi-Cox staining was used to examine the morphological changes of hippocampal neuronal dendrites. Neuronal apoptosis in the hippocampal CA3 regions was detected by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining. The levels of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and protein kinase B (AKT) proteins were measured by Western blot analysis. This study showed that CSDP induces depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring mice. Conditional gene knockout of hippocampal Crhr1 in mice reduced CSDP-induced depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring, and counteracted the CSDP-induced decreased expression of p-Akt and mTOR activity in male offspring hippocampus. These findings demonstrated that CSDP might inhibit the Akt/mTOR pathway by increasing the levels of CRH, leading to increased CRH-mediated activation of hippocampal CRHR1, thereby inducing synaptic impairment and apoptosis in hippocampal neurons, which in turn leads to depression-like behavior in offspring.

Thermophilic and mesophilic digestion of high-solid oily food waste: How to ensure long-term and stable continuous operation?

Commonly high lipid in food waste confronts anaerobic digestion with improved energy production and also inhibition risk from the intermediate long chain fatty acids (LCFAs). Combined with operation challenges from anaerobic digestion of food waste itself, coping strategies are necessitated to ensure stable operation for oily food waste (OFW). A parallel thermophilic (TD) and mesophilic digestion (MD) of high-solid OFW was conducted and operated continuously for a long term. It was clarified that challenges were mainly from acidification, trace metal deficiency and LCFA inhibition. Acidification resulted in an abrupt pH decline to even below 6.00, and over 75% drop of biogas production rate. In addition to the requirements of saturated strong alkali to maintain an appropriate range, supplementation of trace metals were proven effective in counteracting the sharp decrease of biogas production rate. The TD was observed more competent in coping with the acidification than the MD, while the TD needed more supplementation of trace metals at approximately 0.10 mg Fe/g chemical oxygen demand (COD)added, 0.01 mg Co/g CODadded and 0.01 mg Ni/g CODadded. The TD was more adaptable in LCFA conversion due to the stronger ability of overcoming the palmitic acid (C16:0) accumulation. The MD experienced a prolonged recovery period owing to LCFA inhibition shortly after acidification. Similar operation performance was ultimately achieved for the TD and MD by the counteractions, with a methane yield and volatile solids (VS) removal efficiency at about 0.60 L/g VSadded and 75.0%, respectively. In summary, combined pH control and trace metal supplementation, and prevention and recovery of LCFA inhibition were necessary for the stability insurance of a long-term continuous digestion of oily food waste.

An Improvement Method for Improving the Surface Defect Detection of Industrial Products Based on Contour Matching Algorithms.

Aiming at the problems of the poor robustness and universality of traditional contour matching algorithms in engineering applications, a method for improving the surface defect detection of industrial products based on contour matching algorithms is detailed in this paper. Based on the image pyramid optimization method, a three-level matching method is designed, which can quickly obtain the candidate pose of the target contour at the top of the image pyramid, combining the integral graph and the integration graph acceleration strategy based on weak classification. It can quickly obtain the rough positioning and rough angle of the target contour, which greatly improves the performance of the algorithm. In addition, to solve the problem that a large number of duplicate candidate points will be generated when the target candidate points are expanded, a method to obtain the optimal candidate points in the neighborhood of the target candidate points is designed, which can guarantee the matching accuracy and greatly reduce the calculation amount. In order to verify the effectiveness of the algorithm, functional test experiments were designed for template building function and contour matching function, including uniform illumination condition, nonlinear condition and contour matching detection under different conditions. The results show that: (1) Under uniform illumination conditions, the detection accuracy can be maintained at about 93%. (2) Under nonlinear illumination conditions, the detection accuracy can be maintained at about 91.84%. (3) When there is an external interference source, there will be a false detection or no detection, and the overall defect detection rate remains above 94%. It is verified that the proposed method can meet the application requirements of common defect detection, and has good robustness and meets the expected functional requirements of the algorithm, providing a strong technical guarantee and data support for the design of embedded image sensors in the later stage.

CCSI: Continual Class-Specific Impression for data-free class incremental learning.

In real-world clinical settings, traditional deep learning-based classification methods struggle with diagnosing newly introduced disease types because they require samples from all disease classes for offline training. Class incremental learning offers a promising solution by adapting a deep network trained on specific disease classes to handle new diseases. However, catastrophic forgetting occurs, decreasing the performance of earlier classes when adapting the model to new data. Prior proposed methodologies to overcome this require perpetual storage of previous samples, posing potential practical concerns regarding privacy and storage regulations in healthcare. To this end, we propose a novel data-free class incremental learning framework that utilizes data synthesis on learned classes instead of data storage from previous classes. Our key contributions include acquiring synthetic data known as Continual Class-Specific Impression (CCSI) for previously inaccessible trained classes and presenting a methodology to effectively utilize this data for updating networks when introducing new classes. We obtain CCSI by employing data inversion over gradients of the trained classification model on previous classes starting from the mean image of each class inspired by common landmarks shared among medical images and utilizing continual normalization layers statistics as a regularizer in this pixel-wise optimization process. Subsequently, we update the network by combining the synthesized data with new class data and incorporate several losses, including an intra-domain contrastive loss to generalize the deep network trained on the synthesized data to real data, a margin loss to increase separation among previous classes and new ones, and a cosine-normalized cross-entropy loss to alleviate the adverse effects of imbalanced distributions in training data. Extensive experiments show that the proposed framework achieves state-of-the-art performance on four of the public MedMNIST datasets and in-house echocardiography cine series, with an improvement in classification accuracy of up to 51% compared to baseline data-free methods. Our code is available at https://github.com/ubc-tea/Continual-Impression-CCSI.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Structural elucidation and functional characteristics of novel potential prebiotics produced from Limosilactobacillus reuteri N1 GtfB-treated maize starches.

The recently characterized Limosilactobacillus reuteri N1 GtfB (LrN1 GtfB) from glycoside hydrolase family 70 is a novel 4,6-α-glucanotransferase acting on starch/maltooligosaccharides with high enzyme activity and soluble protein yield (in heterogenous system). In this study, the influence of the treatment by LrN1 GtfB on the fine structure and functional characteristics of three maize starches were furtherly investigated and elucidated. Due to the treatment of LrN1 GtfB, the starch molecules were transformed into reuterans containing linear and branched (α1 â†’ 6) linkages with notably smaller molecular weight and shorter chain length. Moreover, the (α1 â†’ 6) linkage ratios in the GtfB-modified high-amylose maize starch (GHMS)/normal maize starch (GNMS)/waxy maize starch (GWMS) increased by 18.3 %/12.6 %/9.0 % as compared to their corresponding controls. In vitro digestibility experiment revealed that the resistant starch content of GHMS, GNMS and GWMS increased by 16 %, 18 % and 25 % as compared to the starch substrates. Furthermore, the butyric acid yielded from GHMS, GNMS and GWMS in the in vitro fermentation experiments were 1.4, 1.5 and 1.4 times higher than those of commercial galactose oligosaccharides. These results indicated that the highly-branched short-clustered reuteran synthesized by LrN1 GtfB might serve as novel potential prebiotics, and provide insights for the synthesis of promising prebiotic dietary fiber from starch.