A systems-biology approach identifies co-expression modules in response to low phosphate supply in maize lines of different breeding history.

Plants cope with low phosphorus availability by adjusting growth and metabolism through transcriptomic and proteomic adaptations. We hypothesize that selected genotypes with distinct phosphorous (P) use efficiency covering the breeding history of European Flint heterotic pool provide a tool to reveal general and genotype-specific molecular responses to P limitation. We reconstructed protein and gene co-expression networks by weighted correlation network analysis and related these to phosphate deficiency-induced traits. In roots, low phosphate supply resulted in a decreasing abundance of proteins in the oxidative pentose phosphate pathway and a negative correlation with root and shoot phosphate content. We observed an increase in abundance and positive correlation with root and shoot phosphate content for proteins in sucrose biosynthesis, lipid metabolism, respiration and RNA processing. Purple acid phosphatases, superoxide dismutase and phenylalanine ammonia lyase were identified as being upregulated under low phosphate in all genotypes. Overall, correlations between protein and mRNA abundance changes were limited, with ribosomal proteins and the ubiquitin protein degradation pathway exclusively responding with protein abundance changes. Carbohydrate, phospho- and sulfo-lipid metabolism showed abundance changes at the protein and mRNA levels. These partially non-overlapping proteomic and transcriptomic adjustments to low phosphate suggest sugar and lipid metabolism as metabolic processes associated with improved P use efficiency specifically in Founder Flint lines. We identified a mitogen-activated protein kinase-kinase as a potential genotype-specific regulator of sucrose metabolism at low phosphate in Founder Flint line EP1. We conclude that, during breedingt of Elite Flint lines, regulation of primary metabolism has changed to result in a distinct low phosphate response in Founder lines.

A Mendelian randomization study on causal effects of 25(OH) vitamin D levels on diabetic nephropathy.

BACKGROUND: Vitamin D supplementation is associated with a lower incidence of diabetic nephropathy (DN); however, whether this association is causative is uncertain. METHODS: We used two-sample Mendelian randomization to examine the causal influence of vitamin D on diabetic nephropathy in 7,751 individuals with type I diabetes-related nephropathy (T1DN) and 9,933 individuals with type II diabetes-related nephropathy (T2DN). Meanwhile, we repeated some previous studies on the influence of KIM-1 (kidney injury molecule 1) and body mass index (BMI) on DN. Additionally, to test the validity of the instruments variable for vitamin D, we conducted two negative controls Mendelian randomization (MR) on breast and prostate cancer, and a positive control MR on multiple sclerosis. RESULTS: Results of the MR analysis showed that there was no causal association between 25(OH)D with the early/later stage of T1DN (early: OR = 0.903, 95%CI: 0.229 to 3.555; later: OR = 1.213, 95%CI: 0.367 to 4.010) and T2DN (early: OR = 0.588, 95%CI: 0.182 to 1.904; later: OR = 0.904, 95%CI: 0.376 to 2.173), nor with the kidney function of patients with diabetes mellitus: eGFRcyea (creatinine-based estimated GFR) (Beta = 0.007, 95%CI: -0.355 to 0.369)) or UACR (urinary albumin creatinine ratio) (Beta = 0.186, 95%CI: -0.961 to 1.333)). CONCLUSIONS: We found no evidence that Vitamin D was causally associated with DN or kidney function in diabetic patients.

LncRNA CCAT1 Protects Astrocytes Against OGD/R-Induced Damage by Targeting the miR-218/NFAT5-Signaling Axis.

Spinal cord injury (SCI) is a grievous neurology-related disorder that causes many devastating symptoms. Emerging roles of long non-coding RNAs (lncRNA) have been shown to play critical roles in multiple neurological diseases. This research planned to dig the function and latent molecular mechanisms of the lncRNA CCAT1 on OGD/R-disposed injury in astrocytes. We observed that CCAT1 expression was diminished and miR-218 expression was elevated in astrocytes during OGD/R. Additionally, an abundance of CCAT1 obviously amplified cell viability and restrained OGD/R-triggered apoptosis in astrocytes, as characterized by reduced levels of pro-apoptotic proteins Bax and C-caspase-3, concomitant with elevated level of anti-apoptotic Bcl-2 protein. Furthermore, administration of CCAT1 remarkably mitigated OGD/R injury-induced neuro-inflammatory responses, reflected in a reduction of inflammatory cytokines including TNF-α, IL-1ß, and IL-6. In action, CCAT1 served as an endogenous sponge effectively downregulating miR-218 expression by binding directly to it, and a negative regulatory relationship between miR-218 and NFAT5. Mechanistically, introduction of miR-218 reversed the inhibitory effects of CCAT1 on OGD/R-induced apoptosis and inflammation damage, which directly resulted from the inhibition of miR-218 and its targeting of NFAT5. Collectively, our study illuminated a new CCAT1/miR-218/NFAT5 regulatory axis in which CCAT1 served as a competing endogenous RNA by sponging miR-218, effectively upregulating NFAT5 expression, thereby alleviating apoptosis and inflammation damage under OGD/R condition. CCAT1 is, therefore, a putative therapeutic target for SCI, based on the results of this study and the potential application of CCAT1 as a neuroprotective agent.

Enhancing Face Recognition With Detachable Self-Supervised Bypass Networks.

Attributed to the development of deep networks and abundant data, automatic face recognition (FR) has quickly reached human-level capacity in the past few years. However, the FR problem is not perfectly solved in case of large poses and uncontrolled occlusions. In this paper, we propose a novel bypass enhanced representation learning (BERL) method to improve face recognition under unconstrained scenarios. The proposed method integrates self-supervised learning and supervised learning together by attaching two auxiliary bypasses, a 3D reconstruction bypass and a blind inpainting bypass, to assist robust feature learning for face recognition. Among them, the 3D reconstruction bypass enforces the face recognition network to encode pose independent 3D facial information, which enhances the robustness to various poses. The blind inpainting bypass enforces the face recognition network to capture more facial context information for face inpainting, which enhances the robustness to occlusions. The whole framework is trained in end-to-end manner with two self-supervised tasks above and the classic supervised face identification task. During inference, the two auxiliary bypasses can be detached from the face recognition network, avoiding any additional computational overhead. Extensive experimental results on various face recognition benchmarks show that, without any cost of extra annotations and computations, our method outperforms state-of-the-art methods. Moreover, the learnt representations can also well generalize to other face-related downstream tasks such as the facial attribute recognition with limited labeled data.

Decreased HMGCS1 inhibits proliferation and inflammatory response of keratinocytes and ameliorates imiquimod-induced psoriasis via the STAT3/IL-23 axis.

Psoriasis is an immuno-inflammatory disease characterized by excessive keratinocyte proliferation, requiring extensive lipids. 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) is an essential enzyme in the mevalonate pathway, involved in cholesterol synthesis and the inflammatory response. However, the role of HMGCS1 in psoriasis has remained elusive. This study aims to elucidate the mechanism by which HMGCS1 controls psoriasiform inflammation. We discovered an increased abundance of HMGCS1 in psoriatic lesions when analyzing two Gene Expression Omnibus (GEO) datasets and confirmed this in psoriatic animal models and psoriatic patients by immunohistochemistry. In a TNF-α stimulated psoriatic HaCaT cell line, HMGCS1 was found to be overexpressed. Knockdown of HMGCS1 using siRNA suppressed the migration and proliferation of HaCaT cells. Mechanistically, HMGCS1 downregulation also reduced the expression of IL-23 and the STAT3 phosphorylation level. In imiquimod-induced psoriatic mice, intradermal injection of HMGCS1 siRNA significantly decreased the expression of HMGCS1 in the epidermis, which in turn led to an improvement in the Psoriasis Area and Severity Index score, epidermal thickening, and pathological Baker score. Additionally, expression levels of inflammatory cytokines IL-23, IL1-ß, chemokine CXCL1, and innate immune mediator S100A7-9 were downregulated in the epidermis. In conclusion, HMGCS1 downregulation improved psoriasis in vitro and in vivo through the STAT3/IL-23 axis.

Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.

Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.

Relationship between bullous pemphigoid and malignancy: A Mendelian randomization study.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, which primarily affects the elderly. However, the relationship between BP and malignancy remains controversial in traditional observational studies. The aim of this study, which included only European populations, was to assess the potential causative link between BP and 13 types of malignant tumors in a two-sample Mendelian randomization (MR) study. BP was not associated with an increased risk of developing 13 types of malignant tumors. This study did not find a causal relationship between BP and malignant tumors. However, further research is warranted to examine the generalizability of this conclusion in non-European populations.

Transceptor NRT1.1 and receptor-kinase QSK1 complex controls PM H+-ATPase activity under low nitrate.

NRT1.1, a nitrate transceptor, plays an important role in nitrate binding, sensing, and nitrate-dependent lateral root (LR) morphology. However, little is known about NRT1.1-mediated nitrate signaling transduction through plasma membrane (PM)-localized proteins. Through in-depth phosphoproteome profiling using membranes of Arabidopsis roots, we identified receptor kinase QSK1 and plasma membrane H+-ATPase AHA2 as potential downstream components of NRT1.1 signaling in a mild low-nitrate (LN)-dependent manner. QSK1, as a functional kinase and molecular link, physically interacts with NRT1.1 and AHA2 at LN and specifically phosphorylates AHA2 at S899. Importantly, we found that LN, not high nitrate (HN), induces formation of the NRT1.1-QSK1-AHA2 complex in order to repress the proton efflux into the apoplast by increased phosphorylation of AHA2 at S899. Loss of either NRT1.1 or QSK1 thus results in a higher T947/S899 phosphorylation ratio on AHA2, leading to enhanced pump activity and longer LRs under LN. Our results uncover a regulatory mechanism in which NRT1.1, under LN conditions, promotes coreceptor QSK1 phosphorylation and enhances the NRT1.1-QSK1 complex formation to transduce LN sensing to the PM H+-ATPase AHA2, controlling the phosphorylation ratio of activating and inhibitory phosphorylation sites on AHA2. This then results in altered proton pump activity, apoplast acidification, and regulation of NRT1.1-mediated LR growth.

Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.

Upregulation of SOCS2 causes mitochondrial dysfunction and promotes ferroptosis in pancreatic cancer cells.

SOCS2 exerts oncogenic effects in a variety of tumors, but its role in pancreatic cancer has not been studied. The purpose of this study was to explore the role of SOCS2 in pancreatic cancer. The expression level of SOCS2 and the content of mitochondrial DNA (mtDNA) in the cells were detected by real-time PCR (qRT-PCR), and SOCS2 was overexpressed in PANC-1 and Capan-2 cells by transfection with pcDNA3.2-SOCS2. CCK-8, cell colony formation assay, and flow cytometry were used respectively to detect the cell proliferation rate, cell colony formation ability, and the level of ROS in the cells. The ATP level, glucose consumption level, and Fe2 + level in the cells were assessed by biochemical assays. And Western blot determined the protein expression levels of SOCS2 as well as ferroptosis-related proteins, namely, SLC7A11, DMT1, TFRC, and FTH. We found that SOCS2 was significantly down-regulated in pancreatic cancer cells. Overexpression of SOCS2 significantly decreased the viability of PANC-1 and Capan-2 cells, reduced the content of mtDNA and the level of ATP, and caused mitochondrial dysfunction with an accumulation of ROS. Aside from these effects, up-regulation of SOCS2 raised the levels of Fe2 +, DMT1 and TFRC, and decreased the level of SLC7A11 and FTH in PANC-1 and Capan-2 cells, thereby inducing the occurrence of ferroptosis. In conclusion, up-regulated SOCS2 may enhance mitochondrial dysfunction and ferroptosis in pancreatic cancer cells, which can be used as a molecular target for the diagnosis and treatment of pancreatic carcinoma.

Fractional erbium:yttrium aluminum garnet laser in the treatment of morphea mouse model.

OBJECTIVE: To assess the efficiency and the mechanism of fractional erbium:yttrium aluminum garnet (Er:YAG) laser for the treatment of morphea in mouse model. BACKGROUND: Morphea is a rare autoimmune disease characterized by excessive collagen deposition in skin. Fractional Er:YAG laser treatment is a promising treatment to improve morphea, despite limited studies about the therapeutic effect and underlying mechanism. METHODS: The mouse model of morphea was established by subcutaneously injecting with bleomycin (BLM). A total of 24 mice received fractional Er:YAG laser treatment once a week for 4 weeks. Objective measurement employed was ultrasonic imaging to measure dermal thickness. Subjective measures included scoring according to the adjusted Localized morphea Cutaneous Assessment Tool (LoSCAT); hematoxylin and eosin (H&E) staining to evaluate the histological grade of fibrosis; and quantitative morphometric studies to determine the expression of transforming growth factor-ß1 (TGF-ß1) and matrix metalloproteinase-1 (MMP1) by immunohistochemistry. RESULTS: In this self-controlled study, fractional Er:YAG laser treatment significantly ameliorate the severity of morphea, including lower clinical score (p < 0.01), decreased dermal thickness (p < 0.001), declined histological grade of fibrosis (p < 0.001), increased MMP1 (p < 0.001), and reduced TGF-ß1 (p < 0.01) expression. CONCLUSIONS: We found that fractional Er:YAG laser treatment of morphea has good clinical, ultrasonic, and histopathologic efficacy, which may be a promising treatment in the future.

An updated meta-analysis investigating the association between DNMTs gene polymorphism andgastric cancer risk.

Gastric cancer (GC) is a prominent global health issue, as it ranks as the fifth most prevalent type of cancer and the fourth most significant cause of cancer-related mortality worldwide. Although H. pylori is known to play a role in the development of GC, genetic factors also play a role in its onset and progression. Recent studies have shown that genetic polymorphisms are strongly associated with the development of GC and that certain single nucleotide polymorphisms (SNPs) can be used as biomarkers for early diagnosis and prevention. Epigenetic disturbances, such as DNA methylation, are involved in the development of GC, and mutations in the DNA methyltransferase (DNMT) gene have been found to increase the risk of GC. However, previous findings on the association between DNMTs SNPs and GC risk have been inconsistent. In this study, an updated meta-analysis of three well-studied and controversial DNMTs polymorphic loci, DNMT1 rs16999593, DNMT3A rs1550117 and DNMT3B rs1569686, was performed to provide more reliable results. It was found that DNMT1 rs16999593 was not associated with GC, DNMT3A rs1550117 may have a positive association with GC risk, and DNMT3B rs1569686 may be a protective factor for GC. These findings may provide valuable information for early diagnosis and prevention of GC, but further studies are needed to confirm these results.

Constructing a multi-functional small urban green space network for green space equity in urban built-up areas: A case study of Harbin, China.

Ensuring equitable access to green spaces in urban built-up areas is not only vital for fostering environmental justice but also aligns with the United Nations Sustainable Development Goals (SDGs). However, there is a noticeable gap in the current body of research regarding the role of small urban green spaces, especially their multifunctionality from an ecosystem services perspective. Taking the urban built-up area of Harbin as an example, this study first applied the Analytic Hierarchy Process to classify the supply and demand of green space into three types. Then, the article further analyzes the potential functional positioning of the newly added green spaces, including ecological and social functions, using Minimum Cumulative Resistance and Point of Interest. Finally, multi-criteria decision models are used to explore the priority and functional positioning of green space and construct a multi-functional and highly-efficient small urban green space network. The results indicate a significant imbalance in green space supply and demand, with severe and medium mismatch areas accounting for 30.17 % and 48.50 %, respectively. By assessing the multifunctionality of small green spaces, we propose guidelines that include five types of areas: Concentrated Development (85.85 km2, 16.94 %), Backup Development (70.74 km2, 14.31 %), Maintenance (304.49 km2, 61.51 %), Protection (14.94 km2, 3.02 %), and Optimization (20.89 km2, 4.22 %). Finally, the article proposes a 277.60 km multifunctional small urban green space network. By examining small urban green spaces, this study crafts a pivotal framework for enhancing green space equity in urban built-up environments, providing valuable insights for policymakers and urban planners. The approach has significant implications for developing multifunctional green networks in varied urban contexts and offers a model for wider application, serving as a reference for achieving green space equity in developing countries globally.

Beneficial effects of triadimefon in overcoming drought stress in soybean at fluorescence stage.

Soybean (Glycine max [L.] Merr.) at fluorescence stage frequently experiences drought stress. Although triadimefon has been observed to improve drought tolerance of plants, reports on its role in drought resistance on leaf photosynthesis and assimilate transport are limited. This study examined the effects of triadimefon on leaf photosynthesis and assimilate transport at fluorescence stage of soybean experiencing drought stress. Results showed that triadimefon application relieved the inhibitory effects of drought stress on photosynthesis and increased RuBPCase activity. Drought increased soluble sugar contents, yet reduced starch content in the leaves by heightening the activities of sucrose phosphate synthase (SPS), fructose-1,6-bisphosphatase (FBP), invertase (INV), and amylolytic enzyme, impeding the translocation of carbon assimilates to roots and reducing plant biomass. Nevertheless, triadimefon elevated starch content and minimized sucrose degradation by augmenting sucrose synthase (SS) activity and restraining the activities of SPS, FBP, INV, and amylolytic enzyme compared with drought alone, regulating the carbohydrate balance of drought-stressed plants. Therefore, triadimefon application could reduce the photosynthesis inhibition and regulate the carbohydrate balance of drought-stressed soybean plants to lessen the impacts of drought on soybean biomass.

LncRNA HOX transcript antisense RNA mediates hyperglycemic-induced injury in the renal tubular epithelial cell via the miR-126-5pAkt axis.

OBJECTIVE: To investigate the involvement of HOX transcript antisense RNA (HOTAIR) in the injury of renal tubular epithelial cells induced by high glucose. Results: In high glucose-induced HK-2 cells, the expression of HOTAIR was upregulated, resulting in suppressed cell proliferation. Meanwhile, HOTAIR upregulates the expression of pro-apoptotic proteins Bax and cleaved caspase-3, while downregulating the expression of the anti-apoptotic protein Bcl-2. Luciferase reporter assays revealed that HOTAIR could target miR-126-5p. Additionally, it was found that the PI3K/Akt signaling pathway serves as a downstream target of miR-126-5p. Knockdown of HOTAIR relieved apoptosis, whereas further inhibition of miR-126-5p led to apoptosis in HK-2 cells. Conclusions: HOTAIR plays a regulatory role in mediating high glucose-induced injuries in HK-2 cells, specifically affecting apoptosis and cell viability, via the miR-126-5p/PI3K/Akt signaling pathway.

Intimate Partner Violence Victimization and Depressive Symptoms in Sichuan, China: Are There Gender Variations?

An emerging body of research has linked intimate partner violence (IPV) victimization with negative mental health outcomes among women in postreform China. However, limited scholarly attention has been given to the independent effects of multiple types of IPV victimization on depressive symptoms among men and women. Little is known if these independent effects will vary by gender in China where research on the association between IPV victimization and mental health did not emerge until fairly recently. Given this research paucity, this study aims to (a) examine the independent effects of different types of lifetime IPV victimization among married men and women in Sichuan province on their self-reported past 30-day depressive symptoms and (b) explore possible gender variations in these effects. The data utilized in this study came from a subsample of married men (N = 1,083) and women (N = 1,185) from the Third Survey of Chinese Women's Social Status 2010, a representative sample of adults aged 18 to 64 in Sichuan province. Statistical analyses indicate that all types of lifetime IPV victimization are significantly and positively associated with past 30-day depressive symptoms for women, whereas for men lifetime experiences of general controlling behavior and sexual IPV were not statistically associated with depressive symptoms. Moreover, the effects of multiple types of IPV victimization on depressive symptoms do not significantly vary by gender. Bearing this gender-neutral pattern in mind, health professionals, governmental officials, and researchers are strongly encouraged to focus on both married men and women in their IPV and mental health intervention, prevention, and treatment endeavors in postreform China.

KL-FGF23-VD Axis in Improving Late-Onset Alzheimer's Disease by Modulating IKK/NF-κB Signal Pathway.

Materials and Methods: LOAD rats and Aß microglia were constructed by using Aß 1-40 and IBO mixture. The effect of KL-FGF23-VD axis on LOAD was investigated by transfecting overexpressing and interfering with KL gene adenovirus, and IKK-16 was added to Aß microglia to explore the effect of KL-FGF23-VD axis on regulation of IKK/NF-κB signaling pathway. Results: The results showed that, in KL-OE group, FGF23 was decreased in the hippocampus of LOAD rats compared with control and KL-si, and the trend was opposite in the KL-si group. The KL-FGF23-VD axis can alleviate inflammatory response, reduce the deposition of Aß, and inhibit activation of the NF-κB pathway and neuron apoptosis in brain tissue of LOAD rats. In Aß microglia, the expression of KL-FGF23-VD axis was consistent with animal experiments. The KL-FGF23-VD axis can inhibit the expression of Aß microglia inflammatory factors and the activation of microglia and NF-κB pathway. Meanwhile, IKK expression was decreased in KL-OE group compared with KL-si and Control. In the IKK-16 addition group, the ability of KL-FGF23-VD axis to inhibit the activation of microglia and NF-κB pathway was enhanced. Conclusions: These findings suggest a potential role of the KL-FGF23-VD axis in AD treatment by regulating the IKK/NF-κB pathway.

A Rapid and Universal Workflow for Label-Free-Quantitation-Based Proteomic and Phosphoproteomic Studies in Cereals.

Proteomics and phosphoproteomics are robust tools to analyze dynamics of post-transcriptional processes during growth and development. A variety of experimental methods and workflows have been published, but most of them were developed for model plants and have not been adapted to high-throughput platforms. Here, we describe an experimental workflow for proteome and phosphoproteome studies tailored to cereal crop tissues. The workflow consists of two parallel parts that are suitable for analyzing protein/phosphoprotein from total proteins and the microsomal membrane fraction. We present phosphoproteomic data regarding quantification coverage and analytical reproducibility for example preparations from maize root and shoot, wheat leaf, and a microsomal protein preparation from maize leaf. To enable users to adjust for tissue specific requirements, we provide two different methods of protein clean-up: traditional ethanol precipitation (PC) and a recently developed technology termed single-pot, solid-phase-enhanced sample preparation (SP3). Both the PC and SP3 methods are effective in the removal of unwanted substances in total protein crude extracts. In addition, two different methods of phosphopeptide enrichment are presented: a TiO2 -based method and Fe(III)-NTA cartridges on a robotized platform. Although the overall number of phosphopeptides is stable across protein clean-up and phosphopeptide enrichment methods, there are differences in the preferred phosphopeptides in each enrichment method. The preferred protocol depends on laboratory capabilities and research objective. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Total protein crude extraction Basic Protocol 2: Total protein clean-up with ethanol precipitation Alternate Protocol 1: Total protein clean-up with SP3 method Basic Protocol 3: Microsomal fraction protein extraction Basic Protocol 4: Protein concentration determination by Bradford assay Basic Protocol 5: In-solution digestion with trypsin Basic Protocol 6: Phosphopeptide enrichment with TiO2 Alternate Protocol 2: Phosphopeptide enrichment with Fe(III)-NTA cartridges Basic Protocol 7: Peptide desalting with C18 material Basic Protocol 8: LC-MS/MS analysis of (phospho)peptides and spectrum matching.

Molecular Mechanism of Aluminum-Induced Oxidative Damage and Apoptosis in Rat Cardiomyocytes.

Aluminum exposure can mediate either acute toxicity or chronic toxicity. Aluminum exerts toxic effects on the cardiovascular system, but there are few studies on its related mechanisms. In this study, we investigated the molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Thirty-two male Wistar rats were randomly divided into four groups, including the control group (GC), low-dose group of aluminum exposure (GL), medium-dose group (GM), and high-dose group (GH), with eight rats in each group. The GL, GM, and GH groups were given 5, 10, and 20 mg/(kg·d) of AlCl3 solution by intraperitoneal injection, and the GC group received intraperitoneal injection of the same volume of normal saline (2 ml/rat/day), 5 times a week for 28 days. At the end of the experiment, the levels of aluminum, malondialdehyde (MDA), plasma lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB), and alpha-hydroxybutyrate dehydrogenase (HBDH) were measured. The pathological changes of myocardium were observed by H&E staining. The apoptosis of cardiomyocytes was detected by TUNEL staining, and the expression of apoptosis-related proteins was determined by western blot. The results showed that the levels of CKMB and HBDH in the GM and GH groups were significantly higher than those in the GC group (P < 0.05). The content of aluminum in the myocardium and serum of the aluminum exposure groups was significantly higher than that of the GC group (P < 0.05). The level of MDA in the GM and GH groups was significantly higher than that in the GC group (P < 0.05). The pathological results showed that vacuolated and hypertrophied cardiomyocytes were found in aluminum exposure groups, especially in the GM and GH groups. The TUNEL staining showed that the apoptosis rate of the aluminum exposure groups was considerably higher than that of the GC group (P < 0.05). Western blot showed that the expression of Bcl-2, an anti-apoptotic protein, in cardiomyocytes of aluminum exposure groups was lower than that of the GC group (P < 0.05), while the levels of Bax and caspase-3 in the cardiomyocytes of the GM and GH groups were higher than those of the GC group (P < 0.05). The experimental results showed that aluminum could accumulate in myocardial tissues and cause damage to cardiomyocytes. It could induce oxidative stress damage by increasing the content of MDA in cardiomyocytes and trigger cardiomyocyte apoptosis by activating the pro-apoptotic proteins caspase-3 and Bax and reducing the anti-apoptotic protein Bcl-2.

Locality-Aware Channel-Wise Dropout for Occluded Face Recognition.

Face recognition remains a challenging task in unconstrained scenarios, especially when faces are partially occluded. To improve the robustness against occlusion, augmenting the training images with artificial occlusions has been proved as a useful approach. However, these artificial occlusions are commonly generated by adding a black rectangle or several object templates including sunglasses, scarfs and phones, which cannot well simulate the realistic occlusions. In this paper, based on the argument that the occlusion essentially damages a group of neurons, we propose a novel and elegant occlusion-simulation method via dropping the activations of a group of neurons in some elaborately selected channel. Specifically, we first employ a spatial regularization to encourage each feature channel to respond to local and different face regions. Then, the locality-aware channel-wise dropout (LCD) is designed to simulate occlusions by dropping out a few feature channels. The proposed LCD can encourage its succeeding layers to minimize the intra-class feature variance caused by occlusions, thus leading to improved robustness against occlusion. In addition, we design an auxiliary spatial attention module by learning a channel-wise attention vector to reweight the feature channels, which improves the contributions of non-occluded regions. Extensive experiments on various benchmarks show that the proposed method outperforms state-of-the-art methods with a remarkable improvement.