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Background: Src homology 2 domain-containing phosphatase 2 (SHP2) is hyper-activated in some solid tumors. Previous findings suggest that the expression of SHP2 in colorectal cancer (CRC) may be associated with prognosis. However, validation with large sample data is lacking. Materials and Methods: Tissue microarrays containing 860 CRCs and 197 mucosal tissues adjacent to the tumors were constructed. Immunohistochemistry was used to evaluate the expression of SHP2. Differences between SHP2 expression and clinicopathological parameters were evaluated. Kaplan–Meier survival curves and log-rank tests were used to analyze the relationships between SHP2 expression and the overall survival of patients. A Cox proportional hazard regression model was used for univariate and multivariate analyses of prognostic factors. Results: SHP2 expression in CRCs tissues was significantly higher than those in adjacent mucosal tissues (P < 0.001). SHP2 expression was related to tumor differentiation, depth of invasion, distant metastasis, vascular tumor thrombus, lymph node metastasis, and TNM classification (P < 0.05). The prognosis of the high-expression group of SHP2 was significantly better than that of the low-expression group (P = 0.008). Univariate analysis showed that the expression of SHP2 was a prognostic factor for CRC (P = 0.008). Multivariate analysis demonstrated that SHP2 remained an independent prognostic factor for CRC (P = 0.033). Conclusion: The expression of SHP2 was significantly higher in CRC tissues than in adjacent normal tissues. High expression of SHP2 was associated with a promising outcome, suggesting that SHP2 may be a favorable prognostic indicator of CRC.

Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system’s monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells’ evasion of the immune system and promoting cancer progression. Additionally, miRNAs also influence metastasis formation, including the establishment of metastatic sites and the transformation of tumor cells into migratory phenotypes. Specifically, dysregulated expression of these genes has been associated with abnormal expression of oncogenes and tumor suppressor genes, thereby facilitating tumor development. This study aims to provide a concise overview of the significance and function of miRNAs in breast cancer, focusing on their involvement as tumor suppressors in the antitumor immune response and as oncogenes in metastasis formation. Furthermore, miRNAs hold tremendous potential as targets for gene therapy due to their ability to modulate specific pathways that can either promote or suppress carcinogenesis. This perspective highlights the latest strategies developed for miRNA-based therapies.

Chronic noise exposure is correlated with gut microbiota dysbiosis and glucose and lipid metabolism disorders. However, evidence on the mechanisms underlying of gut microbiota alterations in chronic noise induced glucose and lipid metabolism disorders is limited, and the potential aftereffects of chronic noise exposure on metabolic disorders remain unclear. In present study, we established chronic daytime and nighttime noise exposure mice models to explore the effects and underlying mechanism of gut microbiota on chronic noise-induced glucose and lipid metabolism disorders. The results showed that exposure to chronic daytime or nighttime noise significantly increased the fasting blood glucose, serum and liver TG levels, impaired glucose tolerance, and decreased serum HDL-C levels and liver TC levels in mice. However, after 4 weeks of recovery, only serum TG of mice in nighttime noise recovery group remained elevated. Besides, exposure to chronic noise reduced the intestinal tight junction protein levels and increased intestinal permeability, while this effect did not completely dissipate even after the recovery period. Moreover, chronic noise exposure changed the gut microbiota and significantly regulated metabolites and metabolic pathways, and further activate hepatic gluconeogenesis CRTC2/CREB-PCK1 signaling pathway and lipid synthesis SREBP1/SCD signaling pathway through intestinal hepatic axis. Together, our findings demonstrated that chronic daytime and nighttime noise exposure could cause the glucose and lipid metabolism disorder by modulating the gut microbiota and serum metabolites, and activating hepatic gluconeogenic CREB/CRTC2-PCK1 signaling and lipid synthesis SREBP1/SCD signaling pathway. The potential aftereffects of noise exposure during wakefulness on metabolic disorders are more significant than that of noise exposure during sleep.

Although there are several treatments available for gastric cancer (GC), the prognosis of the disease is still poor due to many factors, such as late diagnosis and tumor heterogeneity. To identify potential therapeutic targets, bioinformatics techniques and clinical sample validation were employed and prostate transmembrane protein androgen induced 1 (PMEPA1) was selected for further study. In the present study, we found that elevated PMEPA1 expression correlates with a worse prognosis and weaker anti-tumor immunity in GC patients. Moreover, our study showed that PMEPA1 not only influences cell proliferation, clone formation, invasion, and migration in vitro, but also plays an important role in GC progression in vivo. Mechanically, PMEPA1 exerts its oncogenic effects through activating the Wnt/β-catenin signaling pathway. Therefore, PMEPA1 is a potential target for treating GC effectively.

AbstractPurpose Astragaloside IV (AS-IV) is a natural saponin substance extracted from the plant Radix Astragali with anti-inflammatory, antioxidant, anti-apoptotic, and liver-protecting effects. This study was to evaluate the liver protection effect of AS-IV on mice after acute alcohol stimulation.Materials and Methods Mice were orally administrated with AS-IV (50, 150, and 500 mg/kg, respectively), and sodium carboxymethyl cellulose (CMC, 50 mg/kg) daily for 7 days, before giving five alcohol-intragastric injections.Results Results suggested that the levels of serum ALT and AST, liver SOD, GSH-PX, 4-HNE, and MDA, serum and liver TNF-α, IL-1β, and IL-6, serum lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), diamine oxidase (DAO) and Myeloperoxidase (MPO), the mRNA and protein expression of hepatic NLRP3, Caspase-1, IL-1β, and IL-18 were significantly decreased in AS-IV-treated mice compared with the model group. Moreover, the effect of AS-IV on histopathology of liver tissue confirmed its protective function. Furthermore, AS-IV ameliorated the gut microbiota imbalance and adjusted the abundance of the following dysfunctional bacteria closer to the control group: Butyricicoccus, Turicibacter, Akkermansia, Anaerotruncus, and Mucispirillum. A strong correlation between intestinal bacteria and potential biomarkers was found.Conclusion Together, our findings indicated that AS-IV exert the hepatoprotective effect by modulating the gut microbiota imbalance and regulating NLRP3/Caspase-1 signaling pathway.

Doxorubicin (DOX) is a potent chemotherapeutic agent known for its multi-organ toxicity, especially in the heart, which limits its clinical application. The toxic side effects of DOX, including DNA damage, oxidative stress, mitochondrial dysfunction and cell apoptosis, are intricately linked to the involvement of nicotinamide adenine dinucleotide (NAD+). To assess the effectiveness of the NAD+ precursor nicotinamide mononucleotide (NMN) in counteracting the multi-organ toxicity of DOX, a mouse model was established through DOX administration, which led to significant reductions in NAD+ in tissues with evident injury, including the heart, liver and lungs. NMN treatment alleviated both multi-organ fibrosis and mortality in mice. Mechanistically, tissue fibrosis, macrophage infiltration and DOX-related cellular damage, which are potentially implicated in the development of multi-organ fibrosis, could be attenuated by NAD+ restoration. Our findings provide compelling evidence for the benefits of NMN supplementation in mitigating the adverse effects of chemotherapeutic drugs on multiple organs.

A fall k-coloring of a graph G is a proper k-coloring of G such that each vertex has at least one neighbor in each of the other color classes. A graph G which has a fall k-coloring is equivalent to having a partition of the vertex set V(G) in k independent dominating sets. In this paper, we first prove that for any fall k-colorable graph G with order n, the number of edges of G is at least (n(k−1)+r(k−r))/2, where r≡n(modk) and 0≤r≤k−1, and the bound is tight. Then, we obtain that if G is k-colorable (k≥2) and the minimum degree of G is at least k−2k−1n, then G is fall k-colorable and this condition of minimum degree is the best possible. Moreover, we give a simple proof for an NP-hard result of determining whether a graph is fall k-colorable, where k≥3. Finally, we show that there exist an infinite family of fall k-colorable planar graphs for k∈{5,6}.

Optical camera communication (OCC) has been widely employed in various applications as a flexible and cost-effective means of communication both on land and underwater. However, the performance of the OCC system through the water-air interface has not been thoroughly investigated. In this article, we explore the performance of the OCC system in a water-air environment and propose a bubble-wave-mitigation algorithm to pre-process the captured frames of received video. Moreover, we propose a transformer-based neural network to demodulate the transmitted signal, mitigating the deterioration in transmission performance caused by inter-symbol interference (ISI). The experimental results demonstrate that a robust transmission can be achieved in the water-air environment by applying our proposed algorithms and neural network demodulator.

Background: Immunogenic cell death (ICD) triggers adaptive immune responses that aid in anticancer therapy. However, the significance of ICD-associated genes (ICDAGs) in clinical applications and their potential impact on the tumor microenvironment (TME) remains unclear. Methods: The TCGA cohort was divided into different ICD clusters using the method of Consensus clustering. We assessed the clinical results and TME features of various ICD clusters. GSVA quantified the activation of hallmark gene sets. To establish an ICD molecular subtypes-related prognostic model (ICDRPM), we performed LASSO Cox regression analysis on the differentially expressed genes (DEGs) among ICD subtypes. We evaluated the assessment of risk groups by analyzing the proportion of immune cells, the TME, differences in genomic mutation, the efficacy of immunotherapy, and drug sensitivity. To enhance the clinical effectiveness of the ICDRPM, a nomograph was developed. Results: Two distinct molecular subtypes were identified, and changes in ICDRGs were associated with clinical outcomes and TME characteristics of patients. A total of 1162 differentially expressed genes (DEGs) were obtained from two ICD clusters, and an ICDRPS was then developed to predict overall survival (OS). During both internal and external validation, patients classified as high-risk exhibited significantly poorer overall survival compared to those classified as low-risk. Additionally, the ICDRPS (ICD_score) was identified as an independent prognostic indicator for patients with BC, demonstrating excellent predictive performance. Afterward, we constructed a dependable nomogram to improve the practicality of the ICD_score. Furthermore, low-risk individuals showed stronger immunocyte infiltration, higher immune checkpoint expression, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immune checkpoint inhibitors (ICIs). Moreover, individuals categorized as having low or high risk exhibited contrasting sensitivity to anticancer medications. Conclusions: The model constructed for genes related to ICD provided meaningful clinical implications for immunotherapy, and facilitated individualized treatment for BC patients.

The deleterious effects of aflatoxins, especially aflatoxin B1 (AFB1) which are widespread at all stages of food production, on the reproductive system have been widely reported in males. However, it is still far from fully understood about the toxic effect and molecular mechanism after exposure to AFB1 in various testicular cells, especially Sertoli cells (SCs) which provide various energy materials and support to the developing germ cells as nurse cells. In this work, we examined the effects of AFB1 in dairy goat SCs on lactate production and autophagy, and the role of autophagy on AFB1-induced reduction in lactate production. Mechanistically, AFB1 destroyed the energy balance and reduced the secretion of lactate in dairy goat SCs (P

Recent results of density ramp-up (< n _e >/ n _GW = 0.5–0.75) experiment in type-I ELMy H-mode on experimental advanced superconducting tokamak are presented, with a focus on pedestal dynamics and turbulence behavior. With the density increase, a general trend is that the pedestal electron pressure ( p _e ^ped ) decreases while the ELM frequency ( f _ELM ) increases. Especially when < n _e >/ n _GW arrives at ∼ 0.68, a sudden decrease of p _e ^ped and an increase of f _ELM are observed. A quasi-coherent mode (QCM) with a frequency of 200–300 kHz is observed in the pedestal region and appears in both density and magnetic fluctuations. The time evolution of p _e ^ped during the inter-ELM phase is analyzed for different densities. The analysis suggests that the pedestal behavior for < n _e >/ n _GW < 0.68 is mainly attributed to pedestal stability but not due to pedestal transport. It is shown that the resistivity effect on the peeling-ballooning (PB) mode (Zhang et al 2017 Phys. Plasmas 24 062108) could be used to explain the present result. But the sudden decrease of p _e ^ped and increase of f _ELM at < n _e >/ n _GW > 0.68 cannot be attributed to the resistivity effect. It is found that for the plasma with < n _e >/ n _GW > 0.68, the QCM disappears just before ELM and the density pedestal becomes steeper. This implies that the QCM can drive outward particle transport. The steeper density pedestal leads to a narrower pedestal width. A narrower pedestal width will lead to a lower pedestal pressure since PB mode limits the pressure gradient and could explain the observed sudden decrease of p _e ^ped and increase of f _ELM .

The role of Ce one Mn-based catalysts for the selective catalytic reduction of NOx at low temperature is an ongoing debate. Here the authors demonstrate that Ce has a structural promoting effect but impacts negatively on the intrinsic catalytic activity of Mn.

Abstract Plasmodium knowlesi is a zoonotic malaria parasite that has gained increasing medical interest over the past two decades. This zoonotic parasitic infection is prevalent in Southeast Asia and causes many cases with fulminant pathology. Despite several biogeographical restrictions that limit its distribution, knowlesi malaria cases have been reported in different parts of the world due to travelling and tourism activities. Here, breakthroughs and key information generated from recent (over the past five years, but not limited to) studies conducted on P. knowlesi were reviewed, and the knowledge gap in various research aspects that need to be filled was discussed. Besides, challenges and strategies required to control and eradicate human malaria with this emerging and potentially fatal zoonosis were described.

The results of artificial insemination (AI) are adversely affected by changes in sperm motility and function throughout the cryopreservation procedure. The proteome alterations of frozen–thawed spermatozoa with various levels of freezability in dairy goats, however, remain largely unknown. To discover differentially expressed proteins (DEPs) and their roles in dairy goat sperm with high or low freezability (HF or LF), we conducted 4D-DIA quantitative proteomics analysis, the results of which are presented in this work. Additionally, we explored the underlying processes that may lead to the variations in sperm freezing resistance. A total of 263 DEPs (Fold Change > 2.0, p-value < 0.05) were identified between the HF group and LF group in frozen–thawed dairy goat spermatozoa. In our Gene Ontology (GO) enrichment analysis, the DEPs were mostly associated with the regulation of biological processes, metabolic processes, and responses to stress and cellular component biogenesis. Our Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis also revealed that the DEPs were predominantly engaged in oxidative phosphorylation, N-Glycan biosythesis, and cysteine and methionien metabolism. A protein–protein interaction (PPI) network analysis revealed 14 potential proteins (NUDFB8, SDHC, PDIA4, HSPB1, etc.) that might influence the freezability of dairy goat sperm. These findings shed light on the processes underlying alterations in the proteome and sperm freezability, aiding further research on sperm cryopreservation.

Dielectric capacitors have garnered significant attention in recent decades for their wide range of uses in contemporary electronic and electrical power systems. The integration of a high breakdown field polymer matrix with various types of fillers in dielectric polymer nanocomposites has attracted significant attention from both academic and commercial sectors. The energy storage performance is influenced by various essential factors, such as the choice of the polymer matrix, the filler type, the filler morphologies, the interfacial engineering, and the composite structure. However, their application is limited by their large amount of filler content, low energy densities, and low-temperature tolerance. Very recently, the utilization of two-dimensional (2D) materials has become prevalent across several disciplines due to their exceptional thermal, electrical, and mechanical characteristics. Compared with zero-dimensional (0D) and one-dimensional (1D) fillers, two-dimensional fillers are more effective in enhancing the dielectric and energy storage properties of polymer-based composites. The present review provides a comprehensive overview of 2D filler-based composites, encompassing a wide range of materials such as ceramics, metal oxides, carbon compounds, MXenes, clays, boron nitride, and others. In a general sense, the incorporation of 2D fillers into polymer nanocomposite dielectrics can result in a significant enhancement in the energy storage capability, even at low filler concentrations. The current challenges and future perspectives are also discussed.

Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs have already been explored in Sf9 insect cells, a key parameter ensuring VLPs are a viable platform is the VLP spike yield (i.e., spike protein content in VLP), which has largely been unreported. In this study, we show that the common strategy of producing SARS-CoV-2 VLPs by expressing spike protein in combination with the native coronavirus membrane and/or envelope protein forms VLPs, but at a critically low spike yield (~0.04–0.08 mg/L). In contrast, fusing the spike ectodomain to the influenza HA transmembrane domain and cytoplasmic tail and co-expressing M1 increased VLP spike yield to ~0.4 mg/L. More importantly, this increased yield translated to a greater VLP spike antigen density (~96 spike monomers/VLP) that more closely resembles that of native SARS-CoV-2 virus (~72–144 Spike monomers/virion). Pseudotyping further allowed for production of functional alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) SARS-CoV-2 VLPs that bound to the target ACE2 receptor. Finally, we demonstrated the utility of pseudotyped VLPs to test neutralizing antibody activity using a simple, acellular ELISA-based assay performed at biosafety level 1 (BSL-1). Taken together, this study highlights the advantage of pseudotyping over native SARS-CoV-2 VLP designs in achieving higher VLP spike yield and demonstrates the usefulness of pseudotyped VLPs as a surrogate for live virus in vaccine and therapeutic development against SARS-CoV-2 variants.

Abstract Background Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion. To derive greater economic benefit, farmers require more female offspring (does); however, the buck-to-doe offspring sex ratio is approximately 50%. At present, artificial insemination after the separation of X/Y sperm using flow cytometry is the primary means of controlling the sex of livestock offspring. However, flow cytometry has not been successfully utilised for the separation of X/Y sperm aimed at sexing control in dairy goats. Results In this study, a novel, simple goat sperm sexing technology that activates the toll-like receptor 7/8 (TLR7/8), thereby inhibiting X-sperm motility, was investigated. Our results showed that the TLR7/8 coding goat X-chromosome was expressed in approximately 50% of round spermatids in the testis and sperm, as measured from cross-sections of the epididymis and ejaculate, respectively. Importantly, TLR7/8 was located at the tail of the X-sperm. Upon TLR7/8 activation, phosphorylated forms of glycogen synthase kinase α/β (GSK3 α/β) and nuclear factor kappa-B (NF-κB) were detected in the X-sperm, causing reduced mitochondrial activity, ATP levels, and sperm motility. High-motility Y-sperm segregated to the upper layer and the low-motility X-sperm, to the lower layer. Following in vitro fertilisation using the TLR7/8-activated sperm from the lower layer, 80.52 ± 6.75% of the embryos were XX females. The TLR7/8-activated sperm were subsequently used for in vivo embryo production via the superovulatory response; nine embryos were collected from the uterus of two does that conceived. Eight of these were XX embryos, and one was an XY embryo. Conclusions Our study reveals a novel TLR7/8 signalling mechanism that affects X-sperm motility via the GSK3 α/β-hexokinase pathway; this technique could be used to facilitate the efficient production of sexed dairy goat embryos.

The genetic diversity of pkmsp-1 of Malaysian Plasmodium knowlesi isolates was studied recently. However, the study only included three relatively older strains from Peninsular Malaysia and focused mainly on the conserved blocks of this gene. In this study, the full-length pkmsp-1 sequence of recent P. knowlesi isolates from Peninsular Malaysia was characterized, along with Malaysian Borneo and Thailand pkmsp-1 sequences that were retrieved from GenBank. Genomic DNA of P. knowlesi was extracted from human blood specimens and the pkmsp-1 gene was PCR-amplified, cloned, and sequenced. The sequences were analysed for genetic diversity, departure from neutrality, and geographical clustering. The pkmsp-1 gene was found to be under purifying/negative selection and grouped into three clusters via a neighbour-joining tree and neighbour net inferences. Of the four polymorphic blocks in pkmsp-1, block IV, was most polymorphic, with the highest insertion–deletion (indel) sites. Two allelic families were identified in block IV, thereby highlighting the importance of this block as a promising genotyping marker for the multiplicity of infection study of P. knowlesi malaria. A single locus marker may provide an alternate, simpler method to type P. knowlesi in a population.

In mammals, sperm acquire fertilization ability after capacitation in vitro or when in the female reproductive tract. The motility patterns of sperm undergo continuous changes from the moment of ejaculation until fertilization in the female reproductive tract. In vitro, hyperactivated motility can be induced through high glucose mediums, while in vivo, it is induced by oviduct fluids. Conversely, sperm maintain linear motility in seminal plasma or uterine fluids that contain low glucose levels. In dairy goat sperm, energy metabolism associated with capacitation depends on the energy sources in vitro, seminal plasma, or the female reproductive tract, especially the glucose levels. However, there is little experimental knowledge that glucose levels affect sperm energy metabolism in dairy goats. To clarify these hypotheses, we incubated dairy goat spermatozoa with different concentrations of rotenone-glucose (ROT), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), and tigecycline (TIG) in vitro. Sperm motility attributes, ATP content, pyruvate and lactate levels, mitochondrial permeability transition pore fluorescence intensity, mitochondrial membrane potential (MMP), and protein synthesis were analyzed. Sperm motility patterns changed from circular to linear under low glucose conditions compared with those in high glucose conditions and showed a significant improvement in progressive motility and straight line speed, whereas lactate and pyruvate levels and MMP decreased remarkably. Incubation of spermatozoa with ROT, FCCP, and TIG inhibited sperm mitochondrial activity, protein synthesis, oxidative phosphorylation, and ATP levels, thereby reducing sperm motility, including the progressive motility, straight line speed, and total motility. Simultaneously, incubation of spermatozoa with Compound C under low glucose conditions significantly decreased the ATP levels and MMP, as well as liver kinase B1 and AMPK protein expression. Under low glucose conditions, sperm mainly produce ATP through mitochondrial OXPHOS to achieve high speed linear movement, inhibit ferroptosis through the LKB1/AMPK signaling pathway, and further maintain energy metabolism homeostasis.

Abstract. Background:. To investigate the association between TaqI polymorphism of the vitamin D receptor gene and tuberculosis (TB). Methods:. A systematic search was performed in PubMed, Embase, Web of Science, Elsevier Science Direct, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases for case-control study on TaqI gene polymorphism and TB susceptivity. Quality assessment of studies was performed using the Newcastle–Ottawa Scale for the methodological assessment of case-control studies, and R 4.0.5 software was used for the meta-analysis. Results:. Among the 243 selected articles, 27 in the meta-analysis. The meta-analysis showed that the TaqI gene polymorphism allene gene model (t vs T, odds ratio [OR]: 1.12, 95% confidence interval [CI]: 0.99–1.27); dominant model (tt + tT vs TT, OR: 1.12, 95% CI: 0.98–1.29); recessive model (tt vs tT + TT, OR: 1.25, 95% CI: 1.03–1.51); codominant A (tt vs TT, OR: 1.37, 95% CI: 1.00–1.87); codominant B (tT vs TT, OR: 1.09, 95% CI: 0.99–1.19). And subgroup dominant model (tt + tT vs TT, OR: 1.27, 95% CI: 1.03–1.55) in Indianas, recessive model (tt vs tT + TT, OR: 1.49, 95% CI: 1.05–2.11) in Iranians, co-dominant B (tT vs TT, OR: 1.28, 95% CI: 1.03–1.59; OR: 1.42, 95% CI: 1.05–1.93) in Indianas and Iranians. Conclusion:. This meta-analysis suggests a significant association between TB and the risk of TaqI in Iranians and Indians, but the vitamin D receptor polymorphism TaqI was not associated with Chinese. Thus, validation studies will be required to confirm these findings.

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

This paper presents the results of the density scanning experiment on the 2018 EAST campaign to study the effect of gas fueling on energy confinement of the ELMy H-mode. The experiment is carried out in a USN configuration, with neutral beam and lower hybrid wave heating and gas fueling, with the upper triangularity δup ∼ 0.47. The total stored energy, H98, and βN decrease with normalized density. Compared to the variations in temperature at the pedestal, the core temperature decreases more significantly for both Te and Ti, leading to a large reduction in core pressure and an increase in the pedestal electron collisionality ν*e,ped. The increase in ν*e,ped could reduce the pedestal current and result in a decrease in the value of q in the core region. It was observed that the frequency of type I ELMs increases with density and the edge localized mode size becomes smaller at high density plasma. An m/n = 2/2 tearing mode was observed at the core of the plasma and can coexist with a sawtooth at low density plasma while this tearing mode disappeared at high gas fueling plasma. The reversal radius of the sawtooth (where q = 1) moves toward the magnetic axis as density increases. The degradation in performance with density may be due to two reasons: the more monotonic shear q profile and the weakening of the stabilizing effect of fast ions on ion temperature gradient modes at high density by D2 gas fueling. It seems that there is a strong link between core transport and pedestal parameters which are influenced by gas fueling, resulting in a significant degradation of energy confinement.

Water quality prediction is a fundamental and necessary task for the prevention and management of water environment pollution. Due to the fluidity of water, different sections of the same river have similar trends in their water quality. The present water quality prediction methods cannot exploit the correlation between the water quality of each section to deeply capture information because they do not take into account how similar the water quality is between sections. In order to address this issue, this paper constructs a water quality prediction model based on multi-task deep learning, taking the chemical oxygen demand (COD) of the water environment of the Lanzhou portion of the Yellow River as the research object. The multiple sections of correlation are trained and learned in this model at the same time, and the water quality information of each section is shared while retaining their respective heterogeneity, and the hybrid model CNN-LSTM is used for better mining from local to full time series features of water quality information. In comparison to the current single-section water quality prediction, experiments have shown that the model’s mean absolute error (MSE) and root mean square error (RMSE) of the predicted value of the model are decreased by 13.2% and 15.5%, respectively, and that it performs better in terms of time stability and generalization.

Edge localized mode (ELM) mitigation accompanied by density pump-out has been achieved during the application of resonant magnetic perturbation (RMP) with a toroidal mode number of n = 4 on EAST recently. The mean ELM frequency increases by a factor of 2.7 from 86 to 235 Hz with a decreased reduction in ELM loss. The evolution of pedestal electron density measured by a profile reflectometer before and after turning on the RMP current is presented. Both the pedestal density and density gradient show a decrease with application of RMP. The density fluctuation in the pedestal region has been measured by an O-mode fluctuation reflectometer. The broadband density fluctuation with a frequency range of 20–115 kHz is enhanced at the later period of the inter-ELM phase during ELM mitigation. This phenomenon is also observed for magnetic fluctuation measured by magnetic probes mounted in the vacuum vessel. A further study shows that the enhanced broadband fluctuations lead to a decrease in the growth rate of the pedestal density and an increase in divert or particle flux. This result implies that these enhanced broadband fluctuations could lead to an enhancement of outward particle transport. The possible roles of the enhanced fluctuations observed in ELM mitigation are also discussed.

C7H4CuF6NO4, triclinic, P1̄ (no. 2), a = 8.5122(5) Å, b = 8.5458(6) Å, c = 8.8674(6) Å, α = 75.042(3)°, β = 68.601(2)°, γ = 89.809(3)°, V = 577.26(7) Å3, Z = 2, Rgt(F) = 0.0247, wRref(F2) = 0.0625, T = 152.41 K.

The robot control technology combined with a machine vision system provides a feasible method for the autonomous operation of moving target. However, designing an effective visual servo control system is a great challenge. For the autonomous operation of the objects moving on the pipeline, this article is dedicated to developing a capture and placement control system for the six degrees of freedom (6-DOF) manipulator equipped with an eye-in-hand camera. Firstly, a path planning strategy of online capture and offline placement is proposed for real-time capture and efficient placement. Subsequently, to achieve the fast, stable, and robust capture for a moving target, a position-based visual servo (PBVS) controller is developed by combining estimated velocity feedforward and refined PID control. Feedforward control is designed using the estimated velocity by a proposed motion estimation method for high response speed. PID control is refined by dead zone constraint to reduce the manipulator’s jitter caused by the frequent adjustment of manipulator control system. Besides, the proportional, integral, and differential coefficients of PID controller are adaptively tuned by fuzzy control to reject the noise, disturbance, and dynamic variation in the capture process. Finally, validation experiments are performed on the constructed ROS–Gazebo simulation platform, demonstrating the effectiveness of the developed control system.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton’s tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.

We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the similar safety as placebo, is the only drug intervention which has been shown to significantly reduce both vertebral and nonvertebral fractures for primary prevention of osteoporotic fractures in PMW; while romosozumab, teriparatide, denosumab, and risedronate are the optimal treatments for secondary prevention when efficacy and safety both considered. A limitation is that safety outcomes failed to consider the severity of adverse effects.

Background: Early screening for colorectal cancer (CRC) is essential to improve its prognosis. Liquid biopsies are increasingly being considered for diagnosing cancer due to low invasiveness and high reproducibility. In addition, circulating extracellular vesicles (crEVs, extracellular vesicles isolated from plasma) expressing tumour-specific proteins are potential biomarkers for various cancers. Here, we present a data-independent acquisition (DIA)-mass spectrometry (MS)-based diagnostic method for liquid biopsies. Methods: Extracellular vesicles (EVs) were isolated from culture supernatants of human CRC cell lines, and plasma of patients with CRC at different tumour stages, by overnight ultracentrifugation coupled with sucrose density gradient centrifugation. Tumour-specific EV proteins were prioritized using Tandem Mass Tag (TMT)-based shotgun proteomics and phosphoproteomics. The results were verified in a second independent cohort and a mouse tumour-bearing model using Western blotting (WB). The candidate biomarkers were further validated in a third cohort by DIA-MS. Finally, the DIA-MS methodology was accelerated to permit high-throughput detection of EV biomarkers in another independent cohort of patients with CRC and healthy controls. Results: High levels of total and phosphorylated fibronectin 1 (FN1) in crEVs, haptoglobin (HP), S100A9 and fibrinogen α chain (FGA) were significantly associated with cancer progression. FGA was the most dominant biomarker candidate. Analysis of the human CRC cell lines and the mouse model indicated that FGA+ crEVs were likely released by CRC cells. Furthermore, fast DIA-MS and parallel reaction monitoring (PRM)-MS both confirmed that FGA+ crEVs could distinguish colon adenoma with an area of curve (AUC) in the receiver operating characteristic (ROC) curve of 0.949 and patients with CRC (AUC of ROC is 1.000) from healthy individuals. The performance outperformed conventional tumour biomarkers. The DIA-MS quantification of FGA+ crEVs among three groups agreed with that from PRM-MS. Conclusion: DIA-MS detection of FGA+ crEVs is a potential rapid and non-invasive screening tool to identify early stage CRC. Abbreviations: FGA: fibrinogen α chain; CRC: colorectal cancer; crEVs: circulating extracellular vesicles; EV: extracellular vesicles;MS: mass spectrometry; WB: Western blotting; ROC: receiver operating characteristic; PRM: Parallel Reaction Monitoring; GPC1: Glypican-1; GO: Gene ontology; TEM: transmission electron microscopy; FN1: Fibronectin 1; HP: haptoglobin; TMT: Tandem Mass Tag; LC-MS/MS: liquid chromatography coupled to tandem mass spectrometry; DIA: data-independent acquisition; DDA: data-dependent acquisition; CiRT: Common internal Retention Time standards;AGC: Automatic gain control; AUC: area under curve.

In a reversed shear discharge in the Experimental Advanced Superconducting Tokamak (EAST), an internal transport barrier (ITB) was formed. For the first time, the turbulence in the plasma core before and after the formation of the ITB in EAST was investigated by microwave reflectometry. It was found that during the formation of the ITB, the turbulence inside the barrier was not completely suppressed. The density fluctuation level decreased in the early phase of ITB and significantly increased later. It was found that the density fluctuation level increased with the density gradient after the appearance of reversed shear Alfvén eigenmodes (RSAEs). The change in turbulence, measurable by the reflectometer, did not affect the rate of increase in core density. Through the measurement of RSAEs, it was found that the formation of this ITB may be related to the minimum q ( q _min ). q _min was close to 2.

The advent of optogenetics provides a well-targeted tool to manipulate neurons because of its high time resolution and cell-type specificity. Recently, closed-loop neural manipulation techniques consisting of optical stimulation and electrical recording have been widely used. However, metal microelectrodes exposed to light radiation could generate photoelectric noise, thus causing loss or distortion of neural signal in recording channels. Meanwhile, the biocompatibility of neural probes remains to be improved. Here, five kinds of neural interface materials are deposited on flexible polyimide-based neural probes and illuminated with a series of blue laser pulses to study their electrochemical performance and photoelectric noises for single-unit recording. The results show that the modifications can not only improve the electrochemical performance, but can also reduce the photoelectric artifacts. In particular, the double-layer composite consisting of platinum-black and conductive polymer has the best comprehensive performance. Thus, a layer of polypeptide is deposited on the entire surface of the double-layer modified neural probes to further improve their biocompatibility. The results show that the biocompatible polypeptide coating has little effect on the electrochemical performance of the neural probe, and it may serve as a drug carrier due to its special micromorphology.

Abstract Background The merozoite of the zoonotic Plasmodium knowlesi invades human erythrocytes via the binding of its Duffy binding protein (PkDBPαII) to the Duffy antigen on the eythrocytes. The Duffy antigen has two immunologically distinct forms, Fya and Fyb. In this study, the erythrocyte-binding assay was used to quantitatively determine and compare the binding level of PkDBPαII to Fya+/b+ and Fya+/b- human erythrocytes. Results In the erythrocyte-binding assay, binding level was determined by scoring the number of rosettes that were formed by erythrocytes surrounding transfected mammalian COS-7 cells which expressed PkDBPαII. The assay result revealed a significant difference in the binding level. The number of rosettes scored for Fya+/b+ was 1.64-fold higher than that of Fya+/b- (155.50 ± 34.32 and 94.75 ± 23.16 rosettes, respectively; t (6) = -2.935, P = 0.026). Conclusions The erythrocyte-binding assay provided a simple approach to quantitatively determine the binding level of PkDBPαII to the erythrocyte Duffy antigen. Using this assay, PkDBPαII was found to display higher binding to Fya+/b+ erythrocytes than to Fya+/b- erythrocytes.

This paper addresses the robust beamforming problem for speech recognition using a novel time-frequency mask estimator. The beamformer first estimates the time-frequency mask using a deep neural network (DNN) based on which the covariance matrices of the target speech and noise are computed. Then, the beamformer coefficients are directly obtained via generalized eigenvector decomposition. To achieve accurate covariance matrix estimation for robust beamforming, we propose a DNN-based mask estimator which can exploit the spatial features of the multi-channel microphone signals. The proposed mask estimator leverages the spatial information of the microphone array by using multi-channel signals to estimate a speech-aware mask and a noise-aware mask simultaneously. Using the target-specified masks, accurate covariance matrices of the target speech and noise can be obtained from the observation independently. Experiments on CHiME4 data sets demonstrate that, compared with the baseline toolkit (BeamformIt) and the winner in the CHiME3 challenge, the proposed method achieves better results both in terms of perceptual speech quality and speech recognition error rate.

In the past decade, sparse and low-rank recovery has drawn much attention in many areas such as signal/image processing, statistics, bioinformatics, and machine learning. To achieve sparsity and/or low-rankness inducing, the ℓ1 norm and nuclear norm are of the most popular regularization penalties due to their convexity. While the ℓ1 and nuclear norm are convenient as the related convex optimization problems are usually tractable, it has been shown in many applications that a nonconvex penalty can yield significantly better performance. In recent, nonconvex regularization-based sparse and low-rank recovery is of considerable interest and it in fact is a main driver of the recent progress in nonconvex and nonsmooth optimization. This paper gives an overview of this topic in various fields in signal processing, statistics, and machine learning, including compressive sensing, sparse regression and variable selection, sparse signals separation, sparse principal component analysis (PCA), large covariance and inverse covariance matrices estimation, matrix completion, and robust PCA. We present recent developments of nonconvex regularization based sparse and low-rank recovery in these fields, addressing the issues of penalty selection, applications and the convergence of nonconvex algorithms. Code is available at https://github.com/FWen/ncreg.git.

Instance segmentation of fruit tree canopies from images acquired by unmanned aerial vehicles (UAVs) is of significance for the precise management of orchards. Although deep learning methods have been widely used in the fields of feature extraction and classification, there are still phenomena of complex data and strong dependence on software performances. This paper proposes a deep learning-based instance segmentation method of litchi trees, which has a simple structure and lower requirements for data form. Considering that deep learning models require a large amount of training data, a labor-friendly semi-auto method for image annotation is introduced. The introduction of this method allows for a significant improvement in the efficiency of data pre-processing. Facing the high requirement of a deep learning method for computing resources, a partition-based method is presented for the segmentation of high-resolution digital orthophoto maps (DOMs). Citrus data is added to the training set to alleviate the lack of diversity of the original litchi dataset. The average precision (AP) is selected to evaluate the metric of the proposed model. The results show that with the help of training with the litchi-citrus datasets, the best AP on the test set reaches 96.25%.

In the satellite communications,there were very high performance requirements for the satellite transponder due to the restrictions of the volume and weight of the load,and the satellite channelization technique was an important means to solve this problem.The overall implementation structure and the sub-channel filter design method which played a serious role in the system were discussed.It has important practical significance to the overall implementation of the digital channelization.

This paper addresses the recovery and demixing problem of signals that are sparse in some general dictionary. Involved applications include source separation, image inpainting, super-resolution, and restoration of signals corrupted by clipping, saturation, impulsive noise, or narrowband interference. We employ the ℓq-norm (0 ≤ q q-minimization formulation for the recovery and demixing problem. This nonconvex formulation is approximately solved by two efficient first-order algorithms based on proximal coordinate descent and alternative direction method of multipliers (ADMM), respectively. The new algorithms are convergent in the nonconvex case under some mild conditions and scale well for high-dimensional problems. A convergence condition of the new ADMM algorithm has been derived. Furthermore, the extension of the two algorithms for multichannels joint recovery has been presented, which can further exploit the joint sparsity pattern among multichannel signals. Various numerical experiments showed that the new algorithms can achieve considerable performance gain over the ℓ1-regularized algorithms.

AIM: To explore the main risk factors related to the incidence of endophthalmitis in patients after cataract surgery in China and to provide evidence for prevention. METHODS: The results of 5 studies on the main risk factors of endophthalmitis in patients after cataract surgery were analyzed by Meta-analysis method. RESULTS: The pooled odds ratio values and 95% CI of age(≥70), diabetes, vitreous overflow, operative time(≥10min), common operating room and control of using time of topical anesthetic were 1.81(95% CI: 1.43-1.69),3.66(95% CI: 1.64-8.16),2.21(95% CI: 1.46-3.32),3.54(95% CI: 2.47-5.06),2.77(95% CI: 2.07-3.72),2.09(95% CI: 1.53-2.86). CONCLUSION: The main risk factors of endophthalmitis were the age(≥70), diabetes, vitreous overflow, operative time(≥10min), common operating room and control of using time of topical anesthetic.

AIM:To explore the main risk factors related to the incidence of cataract in China and to provide evidence for the prevention. METHODS:The results of 17 studies on the main risk factors of cataract were analyzed by Meta-analysis method.RESULTS:The pooled odds ratio values and 95%CI of age, hypertension, diabetes, smoking, presence of merging other eye diseases and long-term exposure to sunlight were 2.48(1.82～3.36),1.88(1.28～2.75),3.55(2.41～5.24),2.58(1.45～4.56),2.39(1.50～3.82),1.82(1.08～3.06). CONCLUSION:The main risk factors of cataract were age, hypertension, diabetes, smoking, presence of merging other eye diseases and long-term exposure to sunlight.

This paper addresses the issue of large covariance matrix estimation in a high-dimensional statistical analysis. Recently, improved iterative algorithms with positive-definite guarantee have been developed. However, these algorithms cannot be directly extended to use a nonconvex penalty for sparsity inducing. In general, a nonconvex penalty has the capability of ameliorating the bias problem of the popular convex lasso penalty, and thus is more advantageous. In this paper, we propose a class of positive-definite covariance estimators using generalized nonconvex penalties. We develop a first-order algorithm based on the alternating direction method framework to solve the nonconvex optimization problem efficiently. The convergence of this algorithm has been proved. Furthermore, the statistical properties of the new estimators have been analyzed for generalized nonconvex penalties. Moreover, extension of this algorithm to covariance estimation from sketched measurements has been considered. The performances of the new estimators have been demonstrated by both a simulation study and a gene clustering example for tumor tissues. Code for the proposed estimators is available at https://github.com/FWen/Nonconvex-PDLCE.git.

Abstract. The syndrome of fever and pancytopenia is not infrequently encountered postliver transplant, and a broad differential list of infectious and noninfectious aetiologies can be invoked. A transplant patient is susceptible to more than 1 opportunistic infection or disease process. We described the diagnostic conundrums in managing our patient who ran a complex protracted course postliver transplant. He was diagnosed to have both disseminated tuberculosis and graft-versus-host disease, a rare complication after solid organ transplantation.

Grape seed procyanidin extract (GSPE) has been shown to possess antioxidative effects. This experiment was designed to study the effect of GSPE during the liquid storage of goat semen. Semen samples were collected from six sexually mature goats. The samples were treated with different concentrations of GSPE (10, 30, 50, and 70 mg/L) in basic diluent and stored at 4 °C for 120 h; samples without GSPE were used as the control group. The results showed that sperm motility, acrosome membrane integrity, mitochondrial activity, plasma membrane integrity, total antioxidative capacity (T-AOC), catalase (CAT) activity, and superoxide dismutase (SOD) activity in the treatment groups were significantly higher than in the control group, whereas malondialdehyde (MDA) content was lower than in the control group (p < 0.05). In the treatment group, sperm quality in the 30 mg/L GSPE group was significantly higher than the other groups (p < 0.05). Furthermore, artificial insemination (AI) results showed that litter sizes were higher in the 30 mg/L GSPE group than in the control group (p < 0.05). In summary, this experiment showed that adding GSPE to the basic diluent improved sperm quality and that 30 mg/L of GSPE was the most suitable concentration for the liquid preservation of goat semen at 4 °C.