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Background Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. Methods To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Results Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Conclusions Our data unveil severity-specific immunological signatures perturbed in CKD patients.

Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested. It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome, which often result in beneficial effects on the health of the host. People call it "prebiotics". In this review, we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides. These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora, and maintain human health, while improving type 2 diabetes-like symptoms such as high blood glucose, and abnormal glucose and lipid metabolism.

Ultrasensitive and specific detection of cocaine is of great significance for monitoring cocaine abuse. Herein, a fluorescent aptasensor via coupling CRISPR-Cas12a, with magnetic nanoparticles (MNPs), split-aptamer, and terminal deoxynucleotidyl transferase (TdT), was developed for the detection of cocaine. In short, the complete cocaine aptamer is split into two parts, one is modified on magnetic nanoparticles (MNPs) and the other is free. The presence of cocaine will mediate the binding of these two segments. Then TdT will mediate the extension to form an ultra-long sequence that can bind with multiple CRISPR-Cas12a resulting in the trans-cleavage activity of CRISPR-Cas12a being triggered. Thence, the DNA reporter which is bi-labeled with fluorophore and quencher is cleaved resulting in the generation of a fluorescence signal. The developed fluorescent aptasensor realizes the detection of cocaine with excellent sensitivity and specificity. The detection limit is low down to 33 pM, and the linear range is from 330 to 1.65 × 10

Background Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. Methods We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). Results Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1–7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79–8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. Conclusions Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. Clinical Trials Registration NCT04647695.

Perfluorodecanoic acid (PFDoA) is a widely distributed environmental pollutant that can affect the functions of many organs. However, systematic evaluations of the effects of PFDoA on testicular functions are lacking. The aim of this study was to investigate the effects of PFDoA on mouse testicular functions, including spermatogenesis, testosterone synthesis, and stem Leydig cells (SLCs) in the interstitial tissue of the testis. PFDoA (0, 2, 5, 10 mg/kg/d) was administered via gavage to 2-month-old mice for 4 weeks. Serum hormone levels and sperm quality were assayed. Furthermore, to investigate the mechanisms by which PFDoA affects testosterone synthesis and spermatogenesis in vivo, the expression of StAR and P450scc in testicular tissue was measured by immunofluorescence staining and quantitative real-time PCR. In addition, the levels of SLC markers, including nestin and CD51, were studied. PFDoA decreased the luteinizing hormone concentration and sperm quality. Although the difference was not statistically significant, mean testosterone levels showed a downward trend. The expression of StAR, P450scc, CD51, and nestin was also suppressed in the PFDoA-treated groups compared with the control group. Our study suggested that PFDoA exposure can decrease testosterone biosynthesis, and even reduce the number of SLCs. These results indicated that PFDoA suppressed the main functions of testis, and further researches are required to identify strategies for preventing or reducing the effect of PFDoA on testicular function.

Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N(6)-methyladenosine (m(6)A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m(6)A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m(6)A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro, as well as tumour growth in vivo. Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m(6)A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m(6)A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.

Cell segmentation’s low precision due to the intensity differences hinders widespread use of whole brain microscopy imaging. Previous studies used ResNet or CNN to account for this problem, but are unapplicable to immunolabeled signals across samples. Here we present a semiauto ground truth generation and weakly-supervised U-Net-based Deep-learning precise segmentation pipeline for whole brain immunopositive c-FOS signals, which reveals the distinct neural activity maps with different social motivations.

Astaxanthin (AST), a super antioxidant with coloring and medical properties, renders it a beneficial feed additive for shrimp. This study conducted a white shrimp feeding trial of 3S, 3’S isoform AST, which was derived from metabolic-engineered Kluyveromyces marxianus fermented broth (TB) and its extract (TE) compared to sources from two chemically synthetic ASTs (Carophyll Pink [CP] and Lucantin Pink [LP]), which contain 3S, 3’S, 3R, 3’S (3S, 3’R) and 3R, 3’R isoforms ratio of 1:2:1. The effects on red coloration, immune parameters and resistance to Vibrio infection were evaluated. Four AST sources were incorporated into the diets at concentrations of 0 (control), 100 mg kg−1 (TB100, TE100, CP100, and LP100), and 200 mg kg−1 (TB200, TE200, CP200, and LP200). Results revealed that in week 4, shrimps that received AST-supplemented feeds, especially TB100, TB200, and TE200, significantly increased redness (a*) values. Immune responses including phagocytosis activity, superoxide-anion production, phenoloxidase activity, and immune-related genes were examined on days 0, 1, 2, 4, 7, 14, 21, and 28. Generally, shrimps that received AST-supplemented feeds exhibited higher immune responses on days 7 and 14 than the control feed. Gene expression levels of superoxide dismutase and glutathione peroxidase were significantly upregulated on days 7 and 14 in shrimps that received AST-supplemented feeds, while genes of penaeidins, antilipopolysaccharide factor, and lysozyme were upregulated on days 4, 7, and 14, especially received TB200 and TE200. Furthermore, shrimps that received TB100, TE100, CP100, and LP100 7 days were then challenged with Vibrio parahaemolyticus and the result demonstrated higher survival rates especially TB100 at 168 h than the control feed. In conclusion, incorporating AST into the diets enhanced shrimp red coloration, immune parameters, and resistance against V. parahaemolyticus infection. The K. marxianus-derived AST exhibited higher performance than did chemical AST to be a potential feed additive in shrimp aquaculture.

The well-posedness of stochastic Navier–Stokes equations with various noises is a hot topic in the area of stochastic partial differential equations. Recently, the consideration of stochastic Navier–Stokes equations involving fractional Laplacian has received more and more attention. Due to the scaling-invariant property of the fractional stochastic equations concerned, it is natural and also very important to study the well-posedness of stochastic fractional Navier–Stokes equations in the associated critical Fourier–Besov spaces. In this paper, we are concerned with the three-dimensional stochastic fractional Navier–Stokes equation driven by multiplicative noise. We aim to establish the well-posedness of solutions of the concerned equation. To this end, by utilising the Fourier localisation technique, we first establish the local existence and uniqueness of the solutions in the critical Fourier–Besov space $$\dot{\mathcal {B}}^{4-2\alpha -\frac{3}{p}}_{p,r}$$ B ˙ p , r 4 - 2 α - 3 p . Then, under the condition that the initial date is sufficiently small, we show the global existence of the solutions in the probabilistic sense.

Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the validity of cerebrospinal fluid (CSF) data in predicting shunt-dependent hydrocephalus (SDHC) in patients with hemorrhagic stroke. PubMed, CENTRAL, and Embase databases were searched for relevant studies published through July 31, 2021. The 16 studies with 1505 patient included those in which CSF data predicted risk for SDHC and reports on CSF parameters in patients in whom SDHC or hydrocephalus that was not shunt-dependent developed following hemorrhagic stroke. We appraised the study quality using Newcastle-Ottawa Scale and conducted a meta-analysis of the pooled estimates of the CSF predictors. The meta-analysis revealed three significant CSF predictors for shunt dependency, i.e., higher protein levels (mean difference [MD] = 32.09 mg/dL, 95% confidence interval [CI] = 25.48-38.70, I

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of

[Au(O4NCS2)]2 underwent structural transformation by heating to give [Au(O4NCS2)]6. Moreover, [Ag(O4NCS2)]n and [Cu(O4NCS2)]4 can be isolated, and notably [Cu(O4NCS2)]4 structurally transformed to [Cu(O4NCS2)]8 by heating can be also observed.

Inspired by crab exoskeleton, fused deposition modeling (FDM) was used to control local deposition of acrylonitrile‐butadiene‐styrene (ABS) polymer and local porosity. Effects of four different meso-scale structures on the stochastic mechanical properties were investigated. Tensile tests showed that the biomimetic Bouligand structure increases strength, strain at break, toughness, and mechanical reliability of additively manufactured porous ABS. Change in meso-scale structures impacted variations in mechanical properties. Weibull moduli--as an indication of variation in properties--ranged from 17 to 54 for fracture strength. Variations in strain at break were higher compared to strength with a Weibull modulus between 6 and 16. Finite element simulations captured the experimental fracture behavior of porous structures. Simulations revealed significant damage accumulation in porous Bouligand structures.

BACKGROUNDThis study is focused to identify the risk factors of shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) and develop a model to predict its incidence.METHODSMedical records of 118 consecutive patients with aSAH treated in our institution from January 2013 to October 2021 were reviewed retrospectively, 109 of them were enrolled in this cohort, the following data were analyzed based on presence or absence of SDHC: age, gender, body mass index, Fisher grade, Hunt and Hess scale (HHS), aneurysm location, treatment modality, new neurological deficits after aneurysm treatment, estimated glomerular filtration rate (eGFR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and platelet-neutrophil ratio (PNR). We conducted univariate and multivariate logistic regression analyses to illustrate a nomogram for predicting SDHC risk.RESULTSThe stepwise logistic regression analysis with backward selection revealed three independent predictive factors of SDHC: age ≥65 (odds ratio, 3.94; 95% CI, 1.4–11.00;p= 0.009), treatment modality (odds ratio, 4.36; 95% CI, 1.81–10.53;p= 0.001), and HHS ≥3 (odds ratio, 3.59; 95% CI, 1.50–8.61;p= 0.004). A nomogram for SDHC risk prediction was developed based on the weight of these 3 factors.CONCLUSIONSAge, treatment modality (clipping vs coiling), and HHS are predictive for SDHC after aSAH. Endovascular embolization of aneurysm plays an important role in reducing risk of SDHC after aSAH.

In this paper, we are concerned with regularity of nonlocal stochastic partial differential equations of parabolic type. By using Campanato estimates and Sobolev embedding theorem, we first show the Hölder continuity (locally in the whole state space \begin{document}$ \mathbb{R}^d $\end{document}) for mild solutions of stochastic nonlocal diffusion equations in the sense that the solutions belong to the space \begin{document}$ C^{\gamma}(D_T;L^p(\Omega)) $\end{document} with the optimal Hölder continuity index \begin{document}$ \gamma $\end{document} (which is given explicitly), where \begin{document}$ D_T: = [0, T]\times D $\end{document} for \begin{document}$ T>0 $\end{document}, and \begin{document}$ D\subset\mathbb{R}^d $\end{document} being a bounded domain. Then, by utilising tail estimates, we are able to obtain the estimates of mild solutions in \begin{document}$ L^p(\Omega;C^{\gamma^*}(D_T)) $\end{document}. What's more, we give an explicit formula between the two indexes \begin{document}$ \gamma $\end{document} and \begin{document}$ \gamma^* $\end{document}. Moreover, we prove Hölder continuity for mild solutions on bounded domains. Finally, we present a new criterion to justify Hölder continuity for the solutions on bounded domains. The novelty of this paper is that our method is suitable to the case of space-time white noise.

Background The Bacillus cereus Sigma B (SigB) dependent general stress response is activated via the two-component RsbKY system, which involves a phosphate transfer from RsbK to RsbY. It has been hypothesized that the Hpr-like phosphocarrier protein (Bc1009) encoded by bc1009 in the SigB gene cluster may play a role in this transfer, thereby acting as a regulator of SigB activation. Alternatively, Bc1009 may be involved in the activation of a subset of SigB regulon members. Results We first investigated the potential role of bc1009 to act as a SigB regulator but ruled out this possibility as the deletion of bc1009 did not affect the expression of sigB and other SigB gene cluster members. The SigB-dependent functions of Bc1009 were further examined in B. cereus ATCC14579 via comparative proteome profiling (backed up by transcriptomics) of wt, Δbc1009 and ΔsigB deletion mutants under heat stress at 42 °C. This revealed 284 proteins displaying SigB-dependent alterations in protein expression levels in heat-stressed cells, including a subgroup of 138 proteins for which alterations were also Bc1009-dependent. Next to proteins with roles in stress defense, newly identified SigB and Bc1009-dependent proteins have roles in cell motility, signal transduction, transcription, cell wall biogenesis, and amino acid transport and metabolism. Analysis of lethal stress survival at 50 °C after pre-adaptation at 42 °C showed intermediate survival efficacy of Δbc1009 cells, highest survival of wt, and lowest survival of ΔsigB cells, respectively. Additional comparative proteome analysis of non-stressed wt and mutant cells at 30 °C revealed 96 proteins with SigB and Bc1009-dependent differences in levels: 51 were also identified under heat stress, and 45 showed significant differential expression at 30 °C. This includes proteins with roles in carbohydrate/ion transport and metabolism. Overlapping functions at 30 °C and 42 °C included proteins involved in motility, and ΔsigB and Δbc1009 cells showed reduced motility compared to wt cells in swimming assays at both temperatures. Conclusion Our results extend the B. cereus SigB regulon to > 300 members, with a novel role of SigB-dependent Bc1009 in the activation of a subregulon of > 180 members, conceivably via interactions with other transcriptional regulatory networks.