GAPDH facilitates homologous recombination repair by stabilizing RAD51 in an HDAC1-dependent manner.

Homologous recombination (HR), a form of error-free DNA double-strand break (DSB) repair, is important for the maintenance of genomic integrity. Here, we identify a moonlighting protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as a regulator of HR repair, which is mediated through HDAC1-dependent regulation of RAD51 stability. Mechanistically, in response to DSBs, Src signaling is activated and mediates GAPDH nuclear translocation. Then, GAPDH directly binds with HDAC1, releasing it from its suppressor. Subsequently, activated HDAC1 deacetylates RAD51 and prevents it from undergoing proteasomal degradation. GAPDH knockdown decreases RAD51 protein levels and inhibits HR, which is re-established by overexpression of HDAC1 but not SIRT1. Notably, K40 is an important acetylation site of RAD51, which facilitates stability maintenance. Collectively, our findings provide new insights into the importance of GAPDH in HR repair, in addition to its glycolytic activity, and they show that GAPDH stabilizes RAD51 by interacting with HDAC1 and promoting HDAC1 deacetylation of RAD51.

Porous NiMoO4 Nanosheet Films and a Device with Ultralarge Optical Modulation for Electrochromic Energy-Storage Applications.

Reducing building energy consumption, improving aesthetics, and improving occupant privacy as well as comfort by dynamically adjusting solar radiation are important application areas for electrochromic (EC) smart windows. However, the current transition metal oxides still cannot meet the requirements of neutral coloration and large optical modulation. We report NiMoO4 nanosheet films directly grown on fluorine-doped tin oxide glasses. The as-grown NiMoO4 film not only achieves neutral coloration from transparent to dark brown but also shows an ultralarge optical modulation (86.8% at 480 nm) and excellent cycling stability (99.4% retention of maximum optical modulation after 1500 cycles). Meanwhile, an EC device demonstrating good EC performance was constructed. These results will greatly promote the research and development of binary transition metal oxides for both EC and energy-storage applications, and NiMoO4 films may be an excellent candidate to replace NiO films as ion-storage layers in complementary EC devices with WO3 films as EC layers.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

MicroRNA-98-5p Inhibits IFI44L-Mediated Differentiation of Dendritic Cells and Activation of Interferon Pathway in Systemic Lupus Erythematosus.

MicroRNA-98-5p (miR-98-5p) plays a protective role in the pathogenesis of autoimmune diseases through anti-inflammatory effects, but little is known about its role in Systemic lupus erythematosus (SLE). Our previous study suggested Interferon-inducible 44 like (IFI44L) overexpressed in monocytes which contributes to the pathogenesis of SLE by enhancing the maturation and functions of monocyte-derived dendritic cells (Mo-DCs), and miR-98-5p can regulate the expression of IFI44L. In this study, we identified miR-98-5p lowly expressed in both peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients along with high expression of IFI44L. IFI44L serves as target gene of miR-98-5p which inhibits differentiation of Mo-DCs and IFI44L-mediated activation of interferon pathway. We further showed that miR-98-5p promotes methylation of the IFI44L promoter to down-regulate its expression in SLE. Our results reveal an important role for miR-98-5p in the IFI44L-mediated immune imbalance of SLE and suggest a potential therapeutic target for SLE in the future.

A Dual-Signal Sensing for the Visual and Luminescent Detection of p-Phenylenediamine Based on Cerium-Nitrogen-Co-Doped Carbon Dots.

Herein, a visual and luminescent dual-mode (colorimetric and fluorometric) method for the detection of P-phenylenediamine (PPD) in hair dye was successfully established based on cerium-nitrogen co-doped carbon dots (Ce, N-CDs) that displayed remarkable luminescence and peroxidase activity. Ce, N-CDs catalyzed H2O2 to produce superoxide anion, which then oxidized the colorless 3,3,5,5-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB), capable of quenching the fluorescence through fluorescence resonance energy transfer (FRET) between Ce, N-CDs and oxTMB. The reducing properties of PPD could reduce oxTMB back to TMB, leading to a decrease in the absorption intensity of oxTMB and a fluorescence recovery of Ce, N-CDs. As a result, the quantitative detection of PPD could be achieved by measuring the absorption values of oxTMB and the fluorescence signal of Ce, N-CDs. The detection limits for PPD were calculated as 0.36 µM and 0.10 µM for colorimetry and fluorimetry, respectively. Furthermore, smartphone application (ColorPicker) capable of measuring the RGB value of the color was utilized in the detection system, facilitating on-site quantitative detection. This approach effectively shortens the detection time and simplifies the operation, offering a powerful and convenient tool for real-time monitoring of PPD.

Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer.

BACKGROUND: Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. METHODS: Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. RESULTS: A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. CONCLUSIONS: This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

SMetABF: A rapid algorithm for Bayesian GWAS meta-analysis with a large number of studies included.

Bayesian methods are widely used in the GWAS meta-analysis. But the considerable consumption in both computing time and memory space poses great challenges for large-scale meta-analyses. In this research, we propose an algorithm named SMetABF to rapidly obtain the optimal ABF in the GWAS meta-analysis, where shotgun stochastic search (SSS) is introduced to improve the Bayesian GWAS meta-analysis framework, MetABF. Simulation studies confirm that SMetABF performs well in both speed and accuracy, compared to exhaustive methods and MCMC. SMetABF is applied to real GWAS datasets to find several essential loci related to Parkinson's disease (PD) and the results support the underlying relationship between PD and other autoimmune disorders. Developed as an R package and a web tool, SMetABF will become a useful tool to integrate different studies and identify more variants associated with complex traits.

EspE3 plays a role in the pathogenicity of avian pathogenic Escherichia coli.

APEC encodes multiple virulence factors that have complex pathogenic mechanisms. In this study, we report a virulence factor named EspE3, which can be secreted from APEC. This protein was predicted to have a leucine-rich repeat domain (LRR) and may have a similar function to IpaH class effectors of the type III secretion system (T3SS). For further exploration, the regulatory correlation between the espE3 and ETT2 genes in APEC was analysed. We then assessed the pathogenicity of EspE3, detected it in APEC secretion proteins and screened the proteins of EspE3 that interact with chicken trachea epithelial cells. This study provides data on a new virulence factor for further exploring the pathogenic mechanism of APEC.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

Mechanism of Escherichia coli Lethality Caused by Overexpression of flhDC, the Flagellar Master Regulator Genes, as Revealed by Transcriptome Analysis.

The flhDC operon of Escherichia coli encodes a transcription factor that initiates flagella synthesis, elevates flagella construction and enhances cell motility, which all are energetically costly and highly regulated processes. In this study, we found that overexpression of flhDC genes from a strong regulatable pN15E6 plasmid could inhibit the growth of E. coli host cells and even eventually cause death. We used transcriptome analysis to investigate the mechanism of flhDC overexpression lethal to host bacteria. The results showed that a total of 568 differentially expressed genes (DEGs), including 378 up-regulated genes and 190 down-regulated genes were detected when the flhDC genes were over-expressed. Functional enrichment analysis results showed that the DEGs are related to a series of crucial biomolecular processes, including flagella synthesis, oxidative phosphorylation and pentose phosphate pathways, etc. We then examined, using RT-qPCR, the expression of key genes of the oxidative phosphorylation pathway at different time points after induction. Results showed that their expression increased in the early stage and decreased afterward, which was suggested to be the result of feedback on the overproduction of ROS, a strong side effect product of the elevated oxidative phosphorylation process. To further verify the level of ROS output, flhDC over-expressed bacteria cells were stained with DCHF-DA and a fluorescence signal was detected using flow cytometry. Results showed that the level of ROS output was higher in cells with over-expressed flhDC than in normal controls. Besides, we found upregulation of other genes (recN and zwf) that respond to ROS damage. This leads to the conclusion that the bacterial death led by the overexpression of flhDC genes is caused by damage from ROS overproduction, which leaked from the oxidative phosphorylation pathway.

Different sensorimotor mechanism in fast and slow progression amyotrophic lateral sclerosis.

The huge heterogeneity of the disease progression rate may cause inconsistent findings between local activity and functional connectivity of the primary sensorimotor area (PSMA) in amyotrophic lateral sclerosis (ALS). For illustration of this hypothesis, resting-state fMRI (RS-fMRI) data were collected and analyzed on 38 "definite" or "probable" ALS patients (19 fast and 19 slow, cut off median = 0.41) and 37 matched healthy controls. Amplitude of low frequency fluctuations (ALFFs) and functional connectivity strength (FCS) were analyzed within the PSMA. There was a decreased ALFF (pFDR <.05) and FCS (p = .022) in all ALS patients. The two metrics shared about 50% of variance (R = .7) and both showed significant positive correlation with ALS Functional Rating Scale-Revised (ALSFRS-R) in the fast (p values <.034) but not in the slow progression groups. Interestingly, when regressing out the ALFF, the PSMA network FCS, especially the inter-hemisphere FCS, showed negative correlation with the ALSFRS-R score in the slow (R = -.54, p = .026) but not the fast progression group. In summary, the current results suggest that RS-fMRI local activity and network functional connectivity accounts for the severity differently in the slow and fast progression ALS patients.

Skin CD4+ Trm cells distinguish acute cutaneous lupus erythematosus from localized discoid lupus erythematosus/subacute cutaneous lupus erythematosus and other skin diseases.

BACKGROUND: Although the contribution of aberrant CD4+ T cell signaling to systemic lupus erythematosus (SLE) is well established, its role in cutaneous lupus erythematosus (CLE) skin is largely unknown. Because the rate of systemic manifestations varies in each subtype, resident memory CD4+ T cells in lesions that are responsible for only skin-associated tissue responses may vary in each subtype. However, the role of CD4+ tissue-resident memory T (CD4+ Trm) cells in each CLE subtype remains unclear. OBJECTIVES: To analyze and compare CD4+ Trm cells and absent in melanoma 2 (AIM2) identified by smart RNA sequencing (Smart-seq) in CD4+ Trm cells from patients with acute CLE (ACLE), subacute CLE (SCLE), and localized discoid lupus erythematosus (localized DLE) lesions. METHODS: We performed Smart-seq to investigate differences in dermal CD4+ Trm cells between patients with ACLE and normal controls (NCs). Multicolor immunohistochemistry was utilized to measure the levels of AIM2 in CD4+ Trm cells present in the skin of 134 clinical patients, which included patients with localized DLE (n = 19), ACLE (n = 19), SCLE (n = 16), psoriasis (n = 12), rosacea (n = 17), lichen planus (n = 18), and annular granuloma (n = 15), as well as NCs (n = 18). RESULTS: The Smart-seq data showed higher AIM2 expression in skin CD4+ Trm cells from ACLE lesions than NCs (fold change >10, adjusted P < 0.05). AIM2 expression in CD4+ Trm cells did not vary according to age or sex. AIM2 expression in CD4+ Trm cells was significantly lower in patients with ACLE (6.38 ± 5.22) than localized DLE (179.41 ± 160.98, P < 0.0001) and SCLE (63.43 ± 62.27, P < 0.05). In an overall comparison of ACLE with localized DLE and SCLE, the receiver operating characteristic curve for AIM2 expression in CD4+ Trm cells had a sensitivity of 100.00% and a specificity of 82.86% at a cutoff value of 18.26. In a comparison of ACLE with localized DLE, the sensitivity was 89.47%, and the specificity was 100.00% at a cutoff value of 12.26. In a comparison of ACLE with SCLE, the sensitivity was 100.00%, and the specificity was 75.00% at a cutoff value of 18.26. CONCLUSIONS: The number of CD4+ Trm cells is increased in lesions of SCLE and localized DLE compared to ACLE, suggesting that CD4+ Trm cells may have a more crucial role in persistent lesions of SCLE and localized DLE. In addition, AIM2 expression in CD4+ Trm cells discriminates patients with ACLE from those with localized DLE and SCLE.

Tight correlation of 5-hydroxymethylcytosine expression with the scarring damage of discoid lupus erythematosus.

OBJECTIVE: Cutaneous lupus erythematosus (CLE) is a heterogenous skin disease. The two most common subtypes are discoid LE (DLE) characterized by scarring skin damage and acute CLE (ACLE) presenting with transiently reversible skin lesions. It remains unknown what causes the difference of skin lesions. Studies have shown the existence of tissue-specific 5-Hydroxymethylcytosine (5 hmC)-modified regions in human tissues, which may affect the tissue-related diseases. Here, we aim to assess the expression of 5 hmc in DLE and ACLE lesions and explore the relationship of 5 hmc with scarring damage in DLE. METHODS: 84 CLE samples were included in the study. We evaluated the skin damage score and reviewed the histopathologic sections. Immunohistochemical staining was performed to detect the expression of 5 hmc in the appendage and periappendageal inflammatory cells. The 5 hmc expression in periappendageal lymphocytic cells was investigated by multi-spectrum immunohistochemistry staining. RESULTS: Scarring/atrophy was the most significant damage in differentiating the DLE from ACLE. Perifollicular inflammatory infiltration was present in all patients with DLE scarring alopecia (DLESA). The 5 hmc expression in the appendage and periappendageal inflammatory cells was significantxly increased in DLESA than ACLE. Similar expression pattern was seen in the staining of IFN-alpha/beta Receptor (IFNAR). The expression of 5 hmc in the appendage was positively correlated with that in the periappendageal inflammatory cells. There was an increased 5 hmc expression in lymphocytes cluster around hair follicle consisting of CD4+ cells, CD8+ cells, and CD19+ cells in DLESA lesions. CONCLUSION: These data demonstrate a close association of the expression pattern of 5 hmc with the histopathological characteristic distribution, and with the type I interferons (IFNs) signals in DLESA, supporting the importance of 5 hmc in the amplification of appendage damage and periappendageal inflammation, thereby offering a novel insight into the scarring damage of DLE and the heterogeneity of CLE skin lesions.

Serum resistance factors in avian pathogenic Escherichia coli mediated by ETT2 gene cluster.

Serum resistance is a poorly understood but common trait of some systemic disease pathogenic strains of bacteria. In this study, we analysed the role Escherichia coli type III secretion system 2 (ETT2) of avian pathogenic Escherichia coli (APEC) in serum resistance by bacteria survival number in serum culture, mRNA Seq and Tandem Mass Tag™ (TMT™) detection, lipopolysaccharide (LPS) extraction, and biofilm formation detection. We found that the ETT2 gene cluster deletion strain (ΔETT2) is more resistant to the killing effect of serum than wild-type APEC40. The analysis of ΔETT2 compared to APEC40 in the transcriptomics and proteomics data showed that ETT2 has a negative effect in the ATP-binding cassette (ABC) translator system and quorum sensing system and a positive effect in purine metabolism. ETT2 may affect the LPS, biofilm, flagella, and fimbriae which may affect the serum resistance. These results could lead to effective strategies for managing the infection by APEC. The mRNA Seq data of this study are available in the Sequence Read Archive of the National Center for Biotechnology Information under the BioProject PRJNA757182, and proteomic raw data have been deposited under the accession number IPX0003420000 at iProX.

Effects of compound probiotics on growth performance, rumen fermentation, blood parameters, and health status of neonatal Holstein calves.

This study aimed to investigate the effects of compound probiotics (consisting of 108 cfu/g of Lactobacillus plantarum, 108 cfu/g of Pediococcus acidilactici, 108 cfu/g of Pediococcus pentosaceus, 107 cfu/g of and Bacillus subtilis) on growth performance, rumen fermentation, bacteria community, blood parameters, and health status of Holstein calves at the first 3 mo of age. Forty-eight newborn calves were randomly divided into the following 3 groups: control group (milk replacer with no compound probiotics), low compound probiotics group (milk replacer + 0.12 g of compound probiotics per head per day), and high compound probiotics group (HP; milk replacer + 1.2 g of compound probiotics per head per day). Starter pellets of the low compound probiotics and HP groups were coated with 0.05% compound probiotics. Milk replacer was provided from 2 to 63 d of age (6 L at 2-10 d, 8 L at 11-42 d, 6 L at 43-49 d, 4 L at 50-56 d, and 2 L at 57-63 d), and starter pellets were provided ad libitum from 7 to 90 d of age. Body weight and body size (d 1, 30, 60, and 90), blood (d 40 and 80), and rumen fluid (d 90) were analyzed using the one-way ANOVA procedure; fecal score was recorded daily and analyzed as repeated measures using the mixed model procedure. Results showed that diet supplemented with compound probiotics had no effects on the body weight, average daily gain, dry matter intake, and feed efficiency. At 90 d of age, diet supplemented with compound probiotics decreased the withers height. Immunity activities increased in the HP group, supported by the increased concentrations of serum total protein and immunoglobulins at 40 d of age, and by the increased activity of superoxide dismutase at 80 d of age. Diet supplemented with compound probiotics altered rumen fermentation, indicated by the decreased rumen acetic acid and propionic acid, and the increased butyric acid concentrations. Diet supplemented with compound probiotics improved the health status of calves, indicated by the decreased fecal score at 3 wk of age and the decreased medicine treatments. In summary, although diet supplemented with HP decreased the withers height, this level of probiotics is recommended to improve rumen development and health status of newborn Holstein calves.

Effects of sea buckthorn (Hippophae rhamnoides L.) on factors related to metabolic syndrome: A systematic review and meta-analysis of randomized controlled trial.

The purpose of this meta-analysis is to explore whether the supplement of sea buckthorn affects the factors related to metabolic syndrome. The related RCTs from five databases were systematically searched and comprehensively random effects model was used to calculate SMD and 95% CI. The Cochrane deviation risk tool was used to evaluate the deviation risk. Fifteen studies were involved in the meta-analysis. First, sea buckthorn supplementation reduced triglycerides [-0.722 (-1.129, -0.316); p < .001], total cholesterol [-0.345 (-0.639, -0.051); p = .021], low density lipoprotein cholesterol [-0.396 (-0.755, -0.037); p = .031], and increased high density lipoprotein cholesterol [0.370 (0.056, 0.684); p = .021] in overall subjects. Second, subgroup analysis showed that sea buckthorn supplementation reduced lipids only in people with abnormal lipid metabolism. Third, sea buckthorn had no effect on blood sugar, blood pressure, and BMI of the overall subjects. Sea buckthorn may affect the lipid metabolism in circulation, but it cannot affect blood glucose, blood pressure, and BMI. These indicators are closely associated with metabolic syndrome. This study may contribute to the development and utilization of sea buckthorn, and may provide a new and safer way for the prevention and treatment of metabolic syndrome. The limitation of this study is high heterogeneity, even if subgroup analysis is used. However, more clinical studies are needed to determine the real effect of sea buckthorn on metabolic syndrome.

Dual projection generalized sidelobe canceller based on mixed signal subspace for ultrasound imaging.

In this paper, we propose a dual projection generalized sidelobe canceller (DPGSC) based on mixed subspace (MS) for ultrasound imaging, which aims to improve the speckle signal-noise-ratio (sSNR) and decrease the dark-region artifacts. A mixed signal subspace based on the correlation between the desired steering vector and the eigenvectors is constructed to further optimize the desired steering vector and the final weight vector. The simulated and experimental results show that the proposed method can greatly improve the speckle uniformity. In the geabr_0 experiment, the standard deviation of background and sSNR of MS-DPGSC can be improved by 48.07% and 58.49% more than those of eigenspace-based generalized sidelobe canceller (ESGSC). Furthermore, for a hyperechoic target, the maximal improvement of contrast ratio is 95.29%. In terms of anechoic cyst, the contrast-to-noise ratio of MS-DPGSC is increased by 123.08% than that of ESGSC. The rat mammary tumor experimental data show that the proposed method has better comprehensive imaging effect than traditional generalized sidelobe cancellers and ESGSCs.

Comparative evaluation for recycling waste power batteries with different collection modes based on Stackelberg game.

The new energy vehicle industry is booming, but the subsequent problem of vehicle power batteries' "scrap tide" is still severe. How to establish and improve the end-of-life power battery recycling system to avoid the "catastrophic" environmental consequences has become an urgent global problem needing a solution. This article constructs three recycling models for manufacturer recycling, retailer recycling, and mixed recycling. By using Stackelberg game and market real data, the influence of carbon trading policy outside the supply chain, power battery endurance capacity and advertising effects within the supply chain on the selection of recycling channels was studied. The results showed: (1) Different recycling channels did not affect the wholesale price, retail price, and market demand for raw material power batteries in the positive supply chain; (2) The total profit function of manufacturers and retailers had a "U-shaped" non-linear relationship with power battery endurance capacity and has a positive linear relationship with the advertising effect. Taking the R&D endurance capacity of 0.4 and the total endurance capacity of 62 kWh as the lowest dividing point, it will decrease first and then increase; (3) The increase in the recycling competition coefficient had a greater impact on the consumption of carbon emission rights in the mixed recycling model than on savings in carbon emission rights, and retailers were the indirect "victims" of rising carbon trading prices; (4) Endurance capacity, advertising effects, and carbon trading prices determined the economics of the recycling model and the carbon emission reduction potential. Manufacturers, retailers, and governments can refer to the value range of each variable to select the most appropriate recycling mode.

A novel humanized cutaneous lupus erythematosus mouse model mediated by IL-21-induced age-associated B cells.

Cutaneous lupus erythematosus (CLE) is a relapsing autoimmune disease, but key elements that drive disease initiation and progression remain elusive. To date, the lack of ideal murine model which resemble human cutaneous lupus makes it extremely challenging for moving mechanistic discoveries and novel therapeutics. Here, we prompt a humanized murine model to develop an inducible rapid-onset murine that performs cutaneous rather than systemic lupus, depending on the successful human immune system reconstruction from active lupus patients and UVB irradiation as for essentially pathogenic triggers. In addition, we demonstrate a newly discovered population of B cell with a unique phenotype, that of the age-associated B cell (ABC, T-bet+ CD11b+), exhibits B cell clusters in humanized cutaneous lupus. In the response of IL-21 and TLR7/9 signals, recruitment of autoreactive B cells to the position of inflammation with subsequent localized antibody production of IgG2a, IgG2b, IgG3, has the potential to exacerbate ongoing inflammation and thus driving lupus-like autoimmunity in a B-cell-dominant fashion. Overall, our model provides a relevant system for exploring the pathophysiology of cutaneous lupus, a suitable model for drug development, as well as updating a potential role of IL-21 and TLR7/9 to be targeted by biologics.