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Abstract Over the past decade, a substantial body of research exploring soundscapes in religious historical buildings has emerged, yet a comprehensive summary of this work is lacking. This paper selects 74 typical studies of soundscapes in religious historical buildings published between 2011 and 2022 to conduct quantitative statistics and visualization analysis from a bibliometric perspective. The selected literature is categorized based on the type of religious building, Christian, Islamic, or Buddhist. The literature is further segmented according to the research subject, including sound field studies, sound analyses, and evaluations of the acoustic environment. The research methods employed are also differentiated and include sound field measurements, acoustic simulations, questionnaires and auralization procedures. The analysis reveals pronounced disparities in research foci depending on the type of religious historical building. For instance, studies on the soundscape in Christian churches tend to focus on objective sound field attributes and frequently employ sound field simulations to analyse the acoustic parameters of diverse church spaces and materials. Conversely, research on the soundscape in Islamic mosques prioritizes speech intelligibility and acoustic comfort, while studies of the soundscape of Buddhist temples gravitate towards the impact of natural and religious sounds on individuals. This paper anticipates the future direction of soundscape research on religious historical buildings. Graphical Abstract

Abstract Brain subcortical structures are paramount in many cognitive functions and their aberrations during infancy are predisposed to various neurodevelopmental and neuropsychiatric disorders, making it highly essential to characterize the early subcortical normative growth patterns. This study investigates the volumetric development and surface area expansion of six subcortical structures and their associations with Mullen scales of early learning by leveraging 513 high-resolution longitudinal MRI scans within the first two postnatal years. Results show that (1) each subcortical structure (except for the amygdala with an approximately linear increase) undergoes rapid nonlinear volumetric growth after birth, which slows down at a structure-specific age with bilaterally similar developmental patterns; (2) Subcortical local area expansion reveals structure-specific and spatiotemporally heterogeneous patterns; (3) Positive associations between thalamus and both receptive and expressive languages and between caudate and putamen and fine motor are revealed. This study advances our understanding of the dynamic early subcortical developmental patterns.

A series of YCe catalysts were prepared using Y-loaded (Y = Cu, Co, Mn) Ce-based metal–organic framework as a precursor. Mn-loaded CeO2 exhibited significantly better catalytic activity in the catalytic oxidation of ethyl acetate (EA) than noble metal catalyst. The relationship between the physicochemical properties of YCe catalysts and catalytic activity was studied by different characterization methods. The enhanced catalytic activity was attributed to the strong interaction between the transition metals and Ce, high specific surface area, abundant lattice defects, more oxygen vacacies and higher Olatt/(Olatt + Oads + Ow) molar ratios. The main intermediates in the oxidation of EA were ethanol, acetic acid, acetone, acetaldehyde and diethyl ether.

Reconstructing 3D structures from non-overlapping multi-view images is a crucial task in the field of 3D computer vision, since it is difficult to establish feature correspondences and infer depth from overlapping parts of views. Previous methods, whether generating the surface mesh or volume of an object, face challenges in simultaneously ensuring the accuracy of detailed topology and the integrity of the overall structure. In this paper, we introduce a novel coarse-to-fine Transformer-based reconstruction network to generate precise point clouds from multiple input images at sparse and non-overlapping viewpoints. Specifically, we firstly employ a general point cloud generation architecture enhanced by the concept of adaptive centroid constraint for the coarse point cloud corresponding to the object. Subsequently, a Transformer-based refinement module applies deformation to each point. We design an attention-based encoder to encode both image projection features and point cloud geometric features, along with a decoder to calculate deformation residuals. Experiments on ShapeNet demonstrate that our proposed method outperforms other competing methods.

Pulp and paper wastewater (PPWW) contains numerous refractory and harmful contaminants that require advanced treatment to meet the discharge criteria. This study compared the efficacy of two PPWW treatments: ultraviolet/peroxymonosulfate (UV/PMS) and ultraviolet/H2O2 (UV/H2O2) working under similar circumstances. The initial pH value, oxidant dosage, UV radiation intensity, and pseudo-first-order constant kobs were systematically studied in both systems. Optimally, the UV/PMS process produced an effluent of higher quality than the UV/H2O2, as measured by the removal efficiencies of chemical oxygen demand (COD) in 60 min, which were 48.2 and 64.3% for the respective UV/H2O2 and UV/PMS processes and corresponding kobs values of 0.0102 and 0.0159 min−1, respectively. Radical scavenging experiments demonstrated that •OH was the primary reactive oxygen species in UV/H2O2 process, and •OH and SO4−• in the UV/PMS process. Moreover, ultraviolet-visible spectroscopy and gas chromatography coupled mass spectroscopy analyses showed that deep treatment of petroleum hydrocarbons with carbon chain lengths greater than 18 and macromolecular semi-volatile organic compounds in paper wastewater is difficult, whereas the UV/PMS process can significantly improve the removal of amides, esters, phenols, and other aromatic compounds. HIGHLIGHTS UV/PMS is a worthwhile in-depth study to achieve more effective treatment of actual wastewater.; It was difficult to completely degrade the organics in actual PPWW due to some long-chain alkanes and macromolecules containing benzene ring organic substances.;

Abstract Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits. Among 1206 variants (average minor allele count = 20, range of 1 to 1064), ~ 43% were not present in publicly available repositories. We identified seven SNV-trait significant associations including a missense SNV at ABCA10 (rs779392624, p = 8 × 10–9) associated with fasting triglycerides, which gene product is involved in macrophage lipid homeostasis. Among non-diabetic individuals, missense SNVs at four genes were associated with fasting insulin adjusted for BMI (PHIL, chr6:79,650,711, p = 2.1 × 10–6; TRPM3, rs760461668, p = 5 × 10–8; SPTY2D1, rs756851199, p = 1.6 × 10–8; and TSPO, rs566547284, p = 2.4 × 10–6). PHIL encoded protein is involved in pancreatic β-cell proliferation and survival, and TRPM3 protein mediates calcium signaling in pancreatic β-cells in response to glucose. A genetic risk score combining increasing insulin risk alleles of these four genes was associated with 53% (95% confidence interval 1.09, 2.15) increased odds of incident diabetes and 83% (95% confidence interval 1.35, 2.48) increased odds of impaired fasting glucose at follow-up. Our study uncovered novel gene-trait associations through the study of protein-coding variants and demonstrates the advantages of association screenings targeting diverse and high-risk populations to study variants absent in publicly available repositories.

Abstract Tumor killing and wound healing are two complementary and influential processes during the treatment of melanoma. Herein, a two-layered microneedle platform was developed with bifunctional effect of chemo-photothermal synergistic melanoma therapy and skin regeneration. The bifunctional platform composed of embeddable curcumin nanodrugs/new Indocyanine Green/hyaluronic acid (Cur NDs/IR820/HA) microneedles and sodium alginate/gelatin/hyaluronic acid (SA/Ge/HA) supporting backing layer was prepared through a two-step casting process. With uniform incorporation of curcumin nanodrugs and IR820, the microneedles exhibited excellent photothermal performance under external near-infrared (NIR) light stimulation and tumor co-therapy ability. Once the embeddable microneedles were inserted into skin, they would rapidly dissolve and activate drug release successfully for tumor treatment. Moreover, the SA/Ge/HA supporting backing layer was left behind to cover the wound and promote the proliferation of endothelial and fibroblasts cells for enhanced skin regeneration. The two-layered microneedles platform can simultaneously eliminate the tumor and accelerate wounding healing, which may be potentially employed as a competitive strategy for the treatment of melanoma. Graphical Abstract

Pectin methylesterase inhibitors (PMEIs) modulate the status of pectin methylesterification by inhibiting the activity of pectin methylesterase (PME). Recent advances indicate PMEIs play an important role in regulating plant cell wall properties and defense responses. In this study, a genome-wide analysis of PMEI gene family in Brassica napus (B. napus) was conducted and the expression patterns of PMEI genes in response to Sclerotinia sclerotiorum (S. sclerotiorum) was investigated. A total of 190 PMEI proteins were identified from the genome of B. napus. Chromosomal location, gene structure and properties of the PMEI family were analyzed, and these features were compared with Arabidopsis thaliana (A. thaliana). A total of 123 syntenic ortholog pairs were detected from BnPMEI family by synteny analysis. Results showed the expansion of BnPMEI genes was likely predominately from whole-genome duplication (WGD) or segmental duplications. Multiple cis-elements related to plant growth and development, environmental stress responses, hormone responses were detected in the promoters of BnPMEI genes, implying they were regulated by both internal and external factors. Furthermore, expression analysis of transcriptome data combined with quantitative RT-PCR (qRT-PCR) validation identified several candidates that were strongly responsive to S. sclerotiorum infection. These BnPMEI genes are candidates for manipulation to breed novel and improved genotypes that are more resistant to sclerotinia stem rot (SSR). Extensive interactions were detected among 30 BnPMEI proteins, forming complex protein-protein interaction networks. Besides, 48 BnPMEIs showed interactions with other proteins including a range of cell wall structure-related enzymes. This study provides new insights into the evolution and function of PMEIs in B. napus and lays a foundation for breeding novel genotypes for crop improvement.

Brain structural traits are highly heritable and have been linked to disease. Here the authors have used gene expression data to perform a transcriptome-wide association study on 211 brain structural traits, discovering 273 associated genes.

Abstract Caching popular contents at base stations (BSs) can effectively avoid redundant data traffic and improve backhaul capacity. Techniques such as multicast (MC) and non‐orthogonal multiple access (NOMA) can significantly improve spectral efficiency by delivering popular contents to multiple users using a single channel. Therefore, we propose a cooperative transmission scheme of MC and NOMA in cache‐enabled wireless cellular networks. First, we derive the probability mass function (PMF) of the number of channels in the MC mode as well as the joint PMF of the number of channels and number of NOMA users in the NOMA mode. Second, we analyse the successful transmission probabilities of the two modes by utilising tools from stochastic geometry. Finally, with the derived probabilities using the two modes, we obtain the total successful transmission probability based on probability theory. The quasi‐closed form expression of the successful transmission probability is obtained in a special case, where the noise is neglected, and the path‐loss exponent is set to be four. Simulation results validate the accuracy of the analysis and demonstrate the performance gain due to the proposed cooperative transmission scheme of MC and NOMA.

Objectives: Stenotrophomonas maltophilia is an important multidrug-resistant pathogen that is associated with various serious nosocomial infections. In our study, we investigated the antimicrobial resistance traits of clinical S. maltophilia strain CYZ isolated from the sputum of an immunocompromised patient. Methods: The whole genome sequence of S. maltophilia CYZ was investigated using a PacBio RS II system. The functions of all the predicted genes were annotated by the COG, GO and KEGG databases. Several types of antibiotics were selected to test the antimicrobial susceptibility, and a phylogenetic tree was constructed based on 16S rRNA gene sequence. Results: The genome of S. maltophilia CYZ has a length of 4,517,685 bp and contains 4077 predicted genes, with an average G + C content of 66.65%. Functional genomic analysis via the annotations of the COG and GO databases revealed that the isolate exhibited specific means to resist antibiotics. The annotated genes involved in flagella, pili or fimbriae, biofilm formation, polysaccharide and cyclic di-GMP may contribute to promote the ability of antimicrobial resistance. This strain showed susceptibility to levofloxacin, trimethoprim/sulfamethoxazole and minocycline according to antimicrobial susceptibility testing. The phylogenetic relationship indicated that S. maltophilia CYZ was closely related to S. maltophilia strains isolated from the nosocomial environment. Conclusions: The current results give a better understanding of the genetic characteristics of antimicrobial resistance in S. maltophilia CYZ and provide a genetic basis for further study of the phenotype.

Abstract Background Immunity reaction plays an essential role in periodontitis progress and we aim to investigate the underlying regulatory network of immune reactions in periodontitis. Methods CIBERSORT was used to estimate immunocyte fractions in different clinical statuses. Logistic regression was used to assess the immunocyte weight in periodontitis. Immune-related periodontitis subtypes were identified by the Nonnegative Matrix Factorization algorithm. Gene-set enrichment analysis and Gene-set variation analysis were conducted to analyze pathway activities. Immunocytes related gene modules were identified by Weighted gene co-expression network analysis. Results Altered immunocytes in healthy versus periodontitis, aggressive versus chronic, male versus female and age were identified. Immunocytes enriched in periodontitis were calculated, and their correlation was also explored. Two distinct immune-related periodontitis subtypes were identified and one is characterized by B cell reactions and the other is IL-6 cytokine reactions. 463 statistically significant correlations between 22 immunocytes and pathways were revealed. Immunocytes and clinical phenotypes matched their gene modules, and their functions were annotated. Last, an easy-to-use and user-friendly interactive web-tool were developed for periodontitis related immune analysis and visualization ( https://118.24.100.193:3838/tool-PIA/ ). Conclusions This study systematically investigated periodontitis immune atlas and caught a glimpse of the underlying mechanism of periodontitis from gene-pathway-immunocyte networks, which can not only inspire researchers but also help them in periodontitis related immune researches.

BRASSINAZOLE RESISTANT (BZR) are transcriptional factors that bind to the DNA of targeted genes to regulate several plant growth and physiological processes in response to abiotic and biotic stresses. However, information on such genes in Brassica napus is minimal. Furthermore, the new reference Brassica napus genome offers an excellent opportunity to systematically characterize this gene family in B. napus. In our study, 21 BnaBZR genes were distributed across 19 chromosomes of B. napus and clustered into four subgroups based on Arabidopsis thaliana orthologs. Functional divergence analysis among these groups evident the shifting of evolutionary rate after the duplication events. In terms of structural analysis, the BnaBZR genes within each subgroup are highly conserved but are distinctive within groups. Organ-specific expression analyses of BnaBZR genes using RNA-seq data and quantitative real-time polymerase chain reaction (qRT-PCR) revealed complex expression patterns in plant tissues during stress conditions. In which genes belonging to subgroups III and IV were identified to play central roles in plant tolerance to salt, drought, and Sclerotinia sclerotiorum stress. The insights from this study enrich our understanding of the B. napus BZR gene family and lay a foundation for future research in improving rape seed environmental adaptability.

Abstract This study developed a novel method for the determination of 13 organophosphate esters (OPEs) in aqueous samples through the optimization of solvent demulsification-dispersive liquid-liquid microextraction based on solidification of floating organic drop procedure coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry. The proposed method was rapid and accurate and could be used in field applications. Under the most suitable conditions, the limit of detection and limit of quantification ranged from 0.16 ng/L to 20.0 ng/L and from 0.55 ng/L to 66.7 ng/L, respectively. The enrichment factors (EFs) ranged from 30 to 46. The relative standard deviations were less than 15%. The spiked recoveries ranged between 68.2% and 97.7% in the analysis of actual aqueous samples. The proposed method was convenient, environment friendly, and time and solvent saving and could be used in field applications compared with other methods. Various concentrations and types of OPEs were detected in tap water, river water, and effluent of sewage treatment plant. Effluent samples had the highest detected levels and types of OPEs.

Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance of chronic infections to antibiotic therapy, the mechanism of their formation has remained elusive. We show that sorted cells of Escherichia coli with low levels of energy-generating enzymes are better able to survive antibiotic killing. Using microfluidics time-lapse microscopy and a fluorescent reporter for in vivo ATP measurements, we find that a subpopulation of cells with a low level of ATP survives killing by ampicillin. We propose that these low ATP cells are formed stochastically as a result of fluctuations in the abundance of energy-generating components. These findings point to a general "low energy" mechanism of persister formation.

Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.

Joint diseases that mainly lead to articular cartilage injury with prolonged severe pain as well as dysfunction have remained unexplained for many years. One of the main reasons is that damaged articular cartilage is unable to repair and regenerate by itself. Furthermore, current therapy, including drug therapy and operative treatment, cannot solve the problem. Fortunately, the micro-/nanoparticle hybrid hydrogel platform provides a new strategy for the treatment of articular cartilage-related diseases, owing to its outstanding biocompatibility, high loading capability, and controlled release effect. The hybrid platform is effective for controlling symptoms of pain, inflammation and dysfunction, and cartilage repair and regeneration. In this review, we attempt to summarize recent studies on the latest development of micro-/nanoparticle hybrid hydrogel for the treatment of articular cartilage-related diseases. Furthermore, some prospects are proposed, aiming to improve the properties of the micro-/nanoparticle hybrid hydrogel platform so as to offer useful new ideas for the effective and accurate treatment of articular cartilage-related diseases.

ABSTRACT Persisters are dormant variants that form a subpopulation of cells tolerant to antibiotics. Persisters are largely responsible for the recalcitrance of chronic infections to therapy. In Escherichia coli, one widely accepted model of persister formation holds that stochastic accumulation of ppGpp causes activation of the Lon protease that degrades antitoxins; active toxins then inhibit translation, resulting in dormant, drug-tolerant persisters. We found that various stresses induce toxin-antitoxin (TA) expression but that induction of TAs does not necessarily increase persisters. The 16S rRNA promoter rrnB P1 was proposed to be a persister reporter and an indicator of toxin activation regulated by ppGpp. Using fluorescence-activated cell sorting (FACS), we confirmed the enrichment for persisters in the fraction of rrnB P1-gfp dim cells; however, this is independent of toxin-antitoxins. rrnB P1 is coregulated by ppGpp and ATP. We show that rrnB P1 can report persisters in a relA/spoT deletion background, suggesting that rrnB P1 is a persister marker responding to ATP. Consistent with this finding, decreasing the level of ATP by arsenate treatment causes drug tolerance. Lowering ATP slows translation and prevents the formation of DNA double-strand breaks upon fluoroquinolone treatment. We conclude that variation in ATP levels leads to persister formation by decreasing the activity of antibiotic targets. IMPORTANCE Persisters are a subpopulation of antibiotic-tolerant cells responsible for the recalcitrance of chronic infections. Our current understanding of persister formation is primarily based on studies of E. coli. The activation of toxin-antitoxin systems by ppGpp has become a widely accepted model for persister formation. In this study, we found that stress-induced activation of mRNA interferase-type toxins does not necessarily cause persister formation. We also found that the persister marker rrnB P1 reports persister cells because it detects a drop in cellular ATP levels. Consistent with this, lowering the ATP level decreases antibiotic target activity and, thus, leads to persister formation. We conclude that stochastic variation in ATP is the main mechanism of persister formation. A decrease in ATP provides a satisfactory explanation for the drug tolerance of persisters, since bactericidal antibiotics act by corrupting energy-dependent targets.

ABSTRACT Persisters are dormant variants that form a subpopulation of drug-tolerant cells largely responsible for the recalcitrance of chronic infections. However, our understanding of the genetic basis of antibiotic tolerance remains incomplete. In this study, we applied transposon sequencing (Tn-Seq) to systematically investigate the mechanism of aminoglycoside tolerance in Escherichia coli. We constructed a highly saturated transposon library that covered the majority of E. coli genes and promoter regions and exposed a stationary-phase culture to a lethal dose of gentamicin. Tn-Seq was performed to evaluate the survival of each mutant to gentamicin exposure. We found that the disruption of several distinct pathways affected gentamicin tolerance. We identified 105 disrupted gene/promoter regions with a more than 5-fold reduction in gentamicin tolerance and 37 genes with a more than 5-fold increased tolerance. Functional cluster analysis suggests that deficiency in motility and amino acid synthesis significantly diminished persisters tolerant to gentamicin, without changing the MIC. Amino acid auxotrophs, including serine, threonine, glutamine, and tryptophan auxotrophs, exhibit strongly decreased tolerance to gentamicin, which cannot be restored by supplying the corresponding amino acids to the culture. Interestingly, supplying these amino acids to wild-type E. coli sensitizes stationary-phase cells to gentamicin, possibly through the inhibition of amino acid synthesis. In addition, we found that the deletion of amino acid synthesis genes significantly increases gentamicin uptake in stationary phase, while the deletion of flagellar genes does not affect gentamicin uptake. We conclude that activation of motility and amino acid biosynthesis contributes to the formation of persisters tolerant to gentamicin. IMPORTANCE Persisters are responsible for the recalcitrance of chronic infections to antibiotics. The pathways of persister formation in E. coli are redundant, and our understanding of the mechanism of persister formation is incomplete. Using a highly saturated transposon insertion library, we systematically analyzed the contribution of different cellular processes to the formation of persisters tolerant to aminoglycosides. Unexpectedly, we found that activation of amino acid synthesis and motility strongly contributes to persister formation. The approach used in this study leads to an understanding of aminoglycoside tolerance and provides a general method to identify genes affecting persister formation.

Because sensing nodes typically have limited power resources, it is extremely important for signals to be acquired with high efficiency and low power consumption, especially in large-scale wireless sensor networks (WSNs) applications. An emerging signal acquisition and compression method called compressed sensing (CS) is a notable alternative to traditional signal processing methods and is a feasible solution for WSNs. In our previous work, we studied several data recovery algorithms and network models that use CS for compressive sampling and signal recovery. The results were validated on large data sets from actual environmental monitoring WSNs. In this paper, we focus on the hardware solution for signal acquisition and processing on separate end nodes. We propose the paradigm of an analog-to-information converter (AIC) based on CS theory. The system model consists of a modulation module, filtering module, and sampling module, and was simulated and analyzed in a MATLAB/Simulink 7.0 environment. Further, the hardware design and implementation of an improved digital AIC system is presented. We also study the performances of three different greedy data recovery algorithms and analyze the system power consumption. The experimental results show that, for normal environmental signals, the new system overcomes the Nyquist limit and exhibits good recovery performance with a low sampling frequency, which is suitable for environmental monitoring based on WSNs.

Video surveillance system (VSS) is increasingly becoming important part in daily life. For traditional VSS, each camera stores streaming data to a centralized server. It will create a great volume of video data for a large VSS and may raise some issues in keeping daily video data to centralized server, such as limited bandwidth and storage insufficiency of server and lower reliability and scalability. In order to solve the problem, we have proposed an architecture for VSS based on well-developed peer-to-peer technique and emerging cloud computing. In this paper, we implement a large-scale VSS (LVSS) and propose an evaluation framework based on the proposed architecture. We implement the LVSS exploits inherent characteristics of P2P and cloud computing to provide an economic, scalable, reliable, and efficient approach to store streaming video. We conducted some experiments to evaluate effectiveness and efficiency of the system. The result shows that the proposed architecture outperforms traditional VSS in terms of effectiveness, efficiency, reliability, and scalability.

The aim of this paper is to extend the lattice method proposed by Ritchken and Trevor (1999) for pricing American options with one-dimensional stochastic volatility models to the two-dimensional cases with strangle payoff. This proposed method is compared with the least square Monte-Carlo method via numerical examples.

BackgroundImmunity reconstitution (IR) is crucial for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), but the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on lymphocyte subsets post-transplant remains unclear. Therefore, we assessed immune cell dynamics in children after SARS-CoV-2 infection.MethodsWe enrolled 42 children, including 21 post-HSCT SARS-CoV-2 infected and 21 matched, non-infected historical controls (1:1 matching based on propensity scores). The time from HSCT to SARS-CoV-2 infection in the infected group was determined by the beginning of follow-up for the non-infected group. The primary endpoint was 270-day IR kinetics post-infection.ResultsOur findings showed similar recovery trends between the infected group and non-infected group both in UCB and HID recipients. In the UCB cohort, the NK cell reconstitution in the infected group was poorer compared to the non-infected group, but this difference did not reach statistical significance (P = 0.178). Furthermore, HID transplantation might be a trend towards poor CD19+ T-cell reconstitution [hazard ratio (HR): 0.43, 95% CI: 0.18–1.04, p = 0.06]. No statistically significant difference was observed in terms of secondary infections across the UCB (P = 0.150) and HID (P = 0.980) cohorts as well as there was no discernible difference in overall survival between the two groups (P = 1).ConclusionsOur analysis reveals that SARS-CoV-2 might temporarily impaired the IR process in the short term, with recovery to a comparable trend as observed in non-infected patients approximately 9 months post-infection.

Abstract Background Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. Methods The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. Results The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. Conclusions This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Abstract Background Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. Methods The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. Results The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells’ proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. Conclusions This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.

BackgroundEncephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication.Case presentationHerein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered.ConclusionWe should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.

[Objective] The effects of different mulching methods on the distribution of organic and inorganic carbon in soil aggregates on the Loess Plateau, and the mechanism under which soil aggregates sequester carbon under mulched conditions were determined in order to promote efficient management of dryland farm soil. [Methods] The study was conducted on a long-term positioning experiment beginning in 2012. Soil characteristics were studied from plots on which spring corn (“Xianyu 335”) was grown under three treatments: straw mulching (SM), film mulching (FM), and no mulching (CK). Carbon distribution and enzyme activities in aggregates of different particle sizes were determined by the wet sieve method. [Results] ① Organic carbon contents of aggregates of each particle size were significantly greater for SM than for CK (p2 mm in size, but significantly increased the reserves of aggregates 2 mm to 0.25 mm in size (p

Abstract Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6–8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (Σ4DEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and Σ4DEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of Σ4DEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and Σ4DEHP in urine were independent risk factors for IPT progression, and Σ4DEHP may be associated with the progression of IPT to CPP or EP.

Neuroblastoma (NB) is an embryonic malignant tumour of the sympathetic nervous system, and current research shows that activation of brown adipose tissue accelerates cachexia in cancer patients. However, the interaction between brown adipose tissues and NB remains unclear. The study aimed to investigate the effect of brown adipocytes in the co-culture system on the proliferation and migration of NB cells. Brown adipocytes promoted the proliferation and migration of Neuro-2a, BE(2)-M17, and SH-SY5Y cells under the co-culture system, with an increase of the mRNA and protein levels of UCP2 and PPAR-γ in NB cells. The UCP2 inhibitor genipin or PPAR-γ inhibitor T0090709 inhibited the migration of NB cells induced by brown adipocytes. Genipin or siUCP2 upregulated the expression of E-cadherin, and downregulated the expression of N-cadherin and vimentin in NB cells. We suggest that under co-cultivation conditions, NB cells can activate brown adipocytes, which triggers changes in various genes and promotes the proliferation and migration of NB cells. The PPAR-γ/UCP2 pathway is involved in the migration of NB cells caused by brown adipocytes.

Abstract Background Radiotherapy is an effective therapeutic approach widely used clinically in non‐small cell lung cancer (NSCLC), but radioresistance remains a major challenge. New and effective radiosensitizing approaches are thus urgently needed. The activation of DNA‐sensing cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway has become an attractive therapeutic target, but the relationship between activation of cGAS‐STING pathway and radiosensitization of NSCLC cells remains unknown. Methods Considering low expression of cGAS‐STING pathway genes in NSCLC, including STING, we used an activator (STING agonist, dimeric amidobenzimidazole [diABZI]) of cGAS‐STING pathway and increased activation factor (DNA double strand breaks) of cGAS‐STING pathway to respectively reinforce the activation of cGAS‐STING pathway in NSCLC cells. We then investigated the effect of increased activation of cGAS‐STING pathway on the proliferation of H460 and A549 cells by CCK‐8 and colony formation assays, and revealed the underlying mechanism. Results We found that both diABZI and the increased DNA double strand breaks could sensitize NSCLC cells to irradiation. Mechanically, our results showed that the increased activation of cGAS‐STING pathway enhanced radiosensitivity by promoting apoptosis in NSCLC cells. Conclusion Taken together, we concluded that diABZI could be used as a radiosensitizer in NSCLC cells, and targeting the activation of cGAS‐STING pathway has a potential to be a new approach for NSCLC radiosensitizing.

This paper aims to examine the impact of executive compensation incentive on corporate innovation capability by dividing executive compensation incentive into short-term monetary incentive and long-term equity incentive. We also investigate the interaction between the two types of executive compensation incentive. Data are collected from China's agro-based companies during 2012-2019, and multiple regression analysis is utilized. The empirical results show that short-term monetary incentive has no impact on innovation capability, while long-term equity incentive stimulates innovation capability. Regarding company ownership, the impact of long-term equity incentive in state-owned enterprises is greater than that in private-owned enterprises. In addition, the complementary effect between short-term and long-term compensation incentive has a positive impact on innovation capability regardless of company ownership. The findings of this paper could help agribusiness managers to design the reasonable incentive system to incentivize corporate executives and enhance the capability of independent innovation.

The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People's Republic of China in July 2020. The current edition was officially implemented on December 30, 2020. The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines, which are the common requirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia. Owing to adherence to the principles of scientificity, versatility, operability, and sustainable development, there is an improvement in the general chapters of the 2020 edition over those of the previous editions. Further, the application of advanced and mature analytical techniques has expanded, the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened, and technical requirements are now better harmonized with international standards. The updated edition provides technical and methodological support to ensure safety, effectiveness, and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technologies, improving the quality control of medicines, and strengthening the means of drug regulation in China. This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.

Objective: Death receptor 4 (DR4; TRAIL-R1) critically mediates extrinsic apoptosis cascades via binding to TNF-related apoptosis-inducing ligand (TRAIL). However, intrinsic and/or acquired resistance are observed in the clinical application of TRAIL. The aim of this study was to investigate the function and molecular mechanism of CD13 in the TRAIL/DR4 pathway against tumor cells, and provide a new strategy for improving therapeutic efficacy or overcoming TRAIL-resistance. Methods: TRAIL protein was expressed as a secretory protein in a Pichia pastoris expression system and was isolated and purified by affinity chromatography. The cell viability and apoptosis were evaluated with MTT (thiazolyl blue tetrazolium bromide) assays and annexin V-FITC/PI staining with flow cytometry analysis, respectively. Western blot analysis was used to detect the levels of the indicated proteins in tumor cells. DR4 degradation or stability was examined with cycloheximide chase assays, and cell surface DR4 was assessed with flow cytometric analysis after staining with a FITC-conjugated antibody. The effects of cell migration were determined with Transwell and gelatin zymography assays. A xenograft nude mouse model was used to detect the anti-tumor effect in vivo, and the proliferation in tumor tissues was examined with immunohistochemical staining. Results: CD13 inhibition potently sensitized tumor cells to TRAIL-induced killing, including proliferation inhibition, increased apoptosis, and migration suppression. In addition, the inhibition of CD13 elevated both total cellular expression and cell surface DR4 through stabilizing DR4 by suppressing its degradation. DR4 siRNA attenuated the enhanced anti-tumor effects of TRAIL plus CD13 inhibition. Interestingly, these phenomena were p-ERK1/2 independent, although p-ERK1/2 down-regulation was tightly correlated with the cooperation of TRAIL and CD13 inhibition. Moreover, a synergistic decrease in tumor growth was surprisingly achieved in the xenograft model by treatment of TRAIL with a CD13 inhibitor (**P < 0.01, CDI = 0.47). Conclusions: CD13 inhibition cooperates with TRAIL in enhancing DR4-mediated cell death, through the up-regulation and stabilization of DR4 in a p-ERK1/2-independent manner. Thus CD13 inhibition has emerged as an effective strategy for TRAIL/DR4-based therapy.

Acute kidney injury (AKI) often impairs the function of other organs leading to distant organ injury. The liver is the major organ that regulates metabolism and lipid homeostasis in the body. It has been reported that AKI causes liver injury with increased oxidative stress, inflammatory response and steatosis. In the present study, we investigated the mechanisms by which ischemia-reperfusion-induced AKI caused hepatic lipid accumulation. Kidney ischemia (45 min)-reperfusion (24 h) led to a significant increase in plasma creatinine and transaminase in Sprague Dawley rats, indicating kidney and liver injury. Histological and biochemical analyses revealed hepatic lipid accumulation with a significant elevation of triglyceride and cholesterol levels in the liver. This was accompanied by a decreased AMP-activated protein kinase (AMPK) phosphorylation, indicating the reduced activation of AMPK, which is an energy sensor that regulates lipid metabolism. The expression of AMPK-regulated genes that were responsible for fatty acid oxidation (CPTIα, ACOX) was significantly decreased, while the expression of lipogenesis genes (SREPB-1c, ACC1) was significantly elevated. The oxidative stress biomarker malondialdehyde was elevated in the plasma and liver. Incubation of HepG2 cells with an oxidative stress inducer hydrogen peroxide inhibited AMPK phosphorylation and caused cellular lipid accumulation. This was accompanied by decreased expression of genes responsible for fatty acid oxidation and increased expression of genes responsible for lipogenesis. These results suggest that AKI elicits hepatic lipid accumulation through decreased fatty acid metabolism and increased lipogenesis. Oxidative stress may contribute, in part, to the downregulation of the AMPK signaling pathway leading to hepatic lipid accumulation and injury.

Due to the rapid growth of network data, the authenticity and reliability of network information have become increasingly important and have presented challenges. Most of the methods for fake review detection start with textual features and behavioral features. However, they are time-consuming and easily detected by fraudulent users. Although most of the existing neural network-based methods address the problems presented by the complex semantics of reviews, they do not account for the implicit patterns among users, reviews, and products; additionally, they do not consider the usefulness of information regarding fine-grained aspects in identifying fake reviews. In this paper, we propose an attention-based multilevel interactive neural network model with aspect constraints that mines the multilevel implicit expression mode of reviews and integrates four dimensions, namely, users, review texts, products and fine-grained aspects, into review representations. We model the relationships between users and products and use these relationships as a regularization term to redefine the model’s objective function. The experimental results from three public datasets show that the model that we propose is superior to the state-of-the-art methods; thus showing the effectiveness and portability of our model.

Purpose. To determine prognostic factors for patients with uveal melanoma without metastases and to construct nomograms to predict their 3- and 5-year overall survival (OS) and cancer-specific survival (CSS). Methods. We included 4119 patients who were registered from 2004 to 2015 in the Surveillance, Epidemiology, and End Results database. The median follow-up time was 5.8 years. Independent risk factors affecting OS and CSS were identified with univariate and multivariate Cox regression analyses and used to construct nomograms. Internal and external validation were carried out by using the bootstrap method to calculate the concordance indices (C-indices) and plot the calibration curves. Results. Age, primary site, histological type, T-stage, and treatment were independent risk factors for OS and CSS; marital status and sequence number were factors only for OS. The C-indices for internal validation of OS and CSS were 0.713 (95% CI, 0.697–0.729) and 0.708 (95% CI, 0.688–0.728), respectively, and for external validation they were 0.729 (95% CI, 0.705–0.753) and 0.731 (95% CI, 0.700–0.762), respectively. The calibration curves also revealed good agreement between the predicted and actual survival rates. Conclusions. We constructed nomograms to predict the 3- and 5-year OS and CSS of patients with uveal melanoma without metastases. Our nomograms may improve prognostication and assist with the development of individualized treatment strategies.

The study of two-dimensional (2D) superconductors is one of the most prominent areas in recent years and has remained a long-standing scientific challenge. Since the introduction of the new member of 2D material family consisting of transition-metal elements with Borides (MBenes), the study of various properties of 2D metal borides has attracted widespread interest. In this work, we systematically investigate the phonon-mediated superconductivity in 2D M B _4 ( M = V, Nb, and Ta), by using the first-principles calculations. Starting from the dynamical stabilities of these structures, we perform a detailed analysis of the electron–phonon coupling and superconductivity of AB-stacked MBenes by solving the anisotropic Eliashberg equation. NbB _4 has the largest electron–phonon coupling and the highest superconducting transition temperature T _c of 35.4 K. Our study broadens the 2D superconducting boride family, which is of great significance for the study of 2D superconductivity.

Phenotype screening has become an important tool for the discovery of active components in traditional Chinese medicine. Anshen Buxin Six Pills (ASBX) are a traditional Mongolian medicine used for the treatment of neurosis in clinical settings. However, its antidepressant components have not been explicitly identified and studied. Here, the antidepressant effect of ASBX was evaluated in adult zebrafish. High performance liquid chromatography-mass spectrometry (HPLC-Q-TOF-MS/MS) was combined with zebrafish behavior trajectory analysis to screen and identify the antidepressant-active extract fraction and active components of ASBX. Finally, the antidepressant effect of the active ingredients were verified by the behavior, pathology, biochemical indices and protein level of adult fish. The novel tank driving test (NTDT) showed that ASBX can effectively improve the depressive effect of reserpine on zebrafish. Petroleum ether and dichloromethane extracts of ASBX were screened as antidepressant active extracts. Costunolide (COS) and dehydrocostus lactone (DHE) were screened as the active components of ASBX. COS had been shown to significantly improve the depressive behavior, nerve injury and neurotransmitter levels (5-hydroxytryptamine (5-HT) and norepinephrine (NE)) of zebrafish by inhibiting the high expression of serotonin transporter and norepinephrine transporter induced by reserpine suggesting the antidepressant effect of COS may be related to its effect on 5-HT and NE pathways. This study provided a phenotype based screening method for antidepressant components of traditional Chinese medicines, so as to realize the separation, identification and activity screening of components at the same time.

Accurate estimation of forest height is crucial for the estimation of forest aboveground biomass and monitoring of forest resources. Remote sensing technology makes it achievable to produce high-resolution forest height maps in large geographical areas. In this study, we produced a 25 m spatial resolution wall-to-wall forest height map in Baoding city, north China. We evaluated the effects of three factors on forest height estimation utilizing four types of remote sensing data (Sentinel-1, Sentinel-2, ALOS PALSAR-2, and SRTM DEM) with the National Forest Resources Continuous Inventory (NFCI) data, three feature selection methods (stepwise regression analysis (SR), recursive feature elimination (RFE), and Boruta), and six machine learning algorithms (k-nearest neighbor (k-NN), support vector machine regression (SVR), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and categorical boosting (CatBoost)). ANOVA was adopted to quantify the effects of three factors, including data source, feature selection method, and modeling algorithm, on forest height estimation. The results showed that all three factors had a significant influence. The combination of multiple sensor data improved the estimation accuracy. Boruta’s overall performance was better than SR and RFE, and XGBoost outperformed the other five machine learning algorithms. The variables selected based on Boruta, including Sentinel-1, Sentinel-2, and topography metrics, combined with the XGBoost algorithm, provided the optimal model (R2 = 0.67, RMSE = 2.2 m). Then, we applied the best model to create the forest height map. There were several discrepancies between the generated forest height map and the existing map product, and the values with large differences between the two maps were mostly distributed in the steep areas with high slope values. Overall, we proposed a methodological framework for quantifying the importance of data source, feature selection method, and machine learning algorithm in forest height estimation, and it was proved to be effective in estimating forest height by using freely accessible multi-source data, advanced feature selection method, and machine learning algorithm.

Acetaminophen (APAP), one of the most common antipyretic analgesics, which is safe at therapeutic dose, cause acute liver injury and even death at overdose. However, the mechanism of APAP-induced inflammation in liver injury is still controversial. Therefore, effective drug intervention is urgently needed. The aim of this study was to explore the inflammatory exact mechanism of APAP, especially on neutrophils, and to study the intervention effect of Chikusetsusaponin V (CKV) derived from Panax japonicus. Establishment of hepatotoxicity model of APAP in vitro and in vivo. In vitro, HepG2 cells, AML12 cells, primary mouse hepatocytes and neutrophils were used to mimic APAP-affected hepatocytes and neutrophil. In vivo, C57BL/6 mice were administrated overdose of APAP with or without neutrophil depletion or abolishing neutrophil extracellular traps (NETs) formation. In this study, APAP stimulation increased the level of HMGB1, IL-1β and Caspase-1 in mouse liver, especially hepatocytes, which had a synergistic effect with LPS/ATP combination. NETs were formatted at early stage of APAP or HMGB1-stimulated neutrophils’ damage. Conditioned mediums from APAP-treated hepatocytes induced more significant NETs than direct APAP stimulation. Neutrophil depletion or abolishing NETs formation decreased HMGB1 level, eventually blocked hepatocytes necrosis. CKV pretreatment interfered Caspase-1 activation and HMGB1 release in APAP-damaged hepatocytes. CKV also prevented NETs formation. These results indicate that the production of HMGB1 may depend on the activation of Caspase-1 and play a key role in liver inflammation caused by APAP. The cross-dialogue between hepatocytes and neutrophils can be mediated by HMGB1. Therefore, CKV has a positive intervention effect on NETs-related inflammation in APAP-damaged liver, targeting Caspase-1-HMGB1.

Abstract Background Cancer cachexia as a metabolic syndrome can lead to at least 25% of cancer deaths. The inhibition of muscle atrophy is a main strategy to treat cancer cachexia. In this process, myostatin (MSTN) can exert a dual effect on protein metabolism, including inhibition of protein biosynthesis and enhancement of protein degradation. In this study, we will test the effect on muscle atrophy induced by cancer cachexia of IMB0901, a MSTN inhibitor. Methods Two high-throughput screening models against MSTN were developed. By screening, IMB0901, 2-((1-(3,4-dichlorophenyl)-1H-pyrazolo [3,4-d] pyrimidin-4-yl) amino) butan-1-ol, was picked out from the compound library. The in vitro cell model and the C26 animal model of muscle atrophy induced by cancer cachexia were used to determine the pharmacological activity of IMB0901. Whether IMB0901 could inhibit the aggravating effect of doxorubicin on muscle wasting was examined in vitro and in vivo. Results IMB0901 inhibited the MSTN promoter activity, the MSTN signaling pathway, and the MSTN positive feedback regulation. In atrophied C2C12 myotubes, IMB0901 had a potent efficiency of decreasing MSTN expression and modulating MSTN signaling pathway which was activated by C26-conditioned medium (CM). In C2C12 myotubes, the expressions of three common myotube markers, myosin heavy chain (MyHC), myogenic differentiation 1 (MyoD), and myogenin (MyoG), were downregulated by CM, which could be efficiently reversed by IMB0901 via reduction of ubiquitin-mediated proteolysis and enhancement of AKT/mTOR-mediated protein synthesis. In the C26 animal model, IMB0901 mitigated the weight loss of body, quadricep and liver, and protected the quadriceps cell morphology. Furthermore, IMB0901 decreased the expression of two E3 ligases Atrogin-1 and MuRF-1 in the quadriceps in vivo. At the cellular level, IMB0901 had no influence on anti-tumor effect of three chemotherapeutic agents (cisplatin, doxorubicin, and gemcitabine) and lowered doxorubicin-induced upregulation of MSTN in C2C12 myotubes. IMB0901 did not affect the inhibitory effect of doxorubicin on C26 tumor and delayed the weight loss of muscle and adipose tissue caused by C26 tumor and doxorubicin. Conclusions IMB0901 inhibits muscle atrophy induced by cancer cachexia by suppressing ubiquitin-mediated proteolysis and promoting protein synthesis. These findings collectively suggest that IMB0901 is a promising leading compound for the management of muscle atrophy induced by cancer cachexia.

The firefly algorithm (FA) is proposed as a heuristic algorithm, inspired by natural phenomena. The FA has attracted a lot of attention due to its effectiveness in dealing with various global optimization problems. However, it could easily fall into a local optimal value or suffer from low accuracy when solving high-dimensional optimization problems. To improve the performance of the FA, this paper adds the self-adaptive logarithmic inertia weight to the updating formula of the FA, and proposes the introduction of a minimum attractiveness of a firefly, which greatly improves the convergence speed and balances the global exploration and local exploitation capabilities of FA. Additionally, a step-size decreasing factor is introduced to dynamically adjust the random step-size term. When the dimension of a search is high, the random step-size becomes very small. This strategy enables the FA to explore solution more accurately. This improved FA (LWFA) was evaluated with ten benchmark test functions under different dimensions (D = 10, 30, and 100) and with standard IEEE CEC 2010 benchmark functions. Simulation results show that the performance of improved FA is superior comparing to the standard FA and other algorithms, i.e., particle swarm optimization, the cuckoo search algorithm, the flower pollination algorithm, the sine cosine algorithm, and other modified FA. The LWFA also has high performance and optimal efficiency for a number of optimization problems.

The aim of this paper is to identify the quantitative impacts of the infectious disease pandemic on the permanent volatility of precious metal and crude oil futures from a long-term perspective by using a recently constructed Infectious Disease Equity Market Volatility Tracker (ID-EMV) to capture the epidemic severity and with a novel mixed data sampling GARCH (GARCH-MIDAS) method. Different from the extant literature only focusing on the short-term influences of the COVID-19 epidemic on commodity futures market, this paper shows that the infectious disease pandemic does have significant and positive impacts on the permanent (long-term) volatilities of precious metal and crude oil futures markets lasting for at least up to 12 months. In addition, these specific impacts on crude oil futures are greater than those on precious metal futures. Finally, we find that the infectious disease epidemic has larger impacts on gold (WTI oil) futures than those on silver (Brent oil) futures. All these findings are robust after controlling the negative influences of lagged long-run realized volatility in commodity futures markets.

Understanding the dependence and risk spillover among hedging assets is crucial for portfolio allocation and regulatory decision making. Using various copula and conditional Value-at-Risk (CoVaR) measures, this paper quantifies the dependence and risk spillover effects between three traditional and emerging hedging assets: Bitcoin, gold, and USD. Furthermore, we investigate these effects at various short- and long-term horizons using a variational model decomposition (VMD) method. The empirical results show that there is strong negative dependence between gold and USD, but Bitcoin and gold are weakly and positively connected. Secondly, risk spillovers exist only between Bitcoin and gold and between gold and USD. The risk spillover effect between Bitcoin and gold are not stable, that is, if Bitcoin or gold faces the downward or upward risk, both the downward and upward risk of another asset have the chance to increase. The negative risk spillover between gold and USD is stable, especially in long-term horizons. Finally, the risk spillover between Bitcoin and gold as well as between gold and USD are asymmetric at downward and upward market environment.

Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are not fully understood. Inflammatory response plays an important role in IR-induced tissue injury. Although increased proinflammatory cytokines have been detected in the kidney and the distant organs after renal IR, their original sources remain uncertain. In the present study, we investigated the acute effect of renal IR on hepatic inflammatory cytokine expression and the mechanism involved. Sprague-Dawley rats that were subjected to renal IR (ischemia for 45 min followed by reperfusion for 1 h or 6 h) had increased plasma levels of creatinine, urea, and transaminases, indicating kidney and liver injuries. There was a significant increase in the expression of proinflammatory cytokine mRNA (MCP-1, TNF-α, IL-6) in the kidney and liver in rats with renal IR. This was accompanied by a significant increase in proinflammatory cytokine protein levels in the plasma, kidney, and liver. Activation of a nuclear transcription factor kappa B (NF-κB) was detected in the liver after renal IR. The inflammatory foci and an increased myeloperoxidase (MPO) activity were detected in the liver after renal IR, indicating hepatic inflammatory response and leukocyte infiltration. These results suggest that renal IR can directly activate NF-κB and induce acute production of proinflammatory cytokines in the liver. Renal IR-induced hepatic inflammatory response may contribute to impaired liver function and systemic inflammation.

Abstract Background Azithromycin is a member of macrolide antibiotics, and has been reported to inhibit the proliferation of cancer cells. However, the underlying mechanisms are not been fully elucidated. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively targets tumor cells without damaging healthy cells. In the present study, we examined whether azithromycin is synergistic with TRAIL, and if so, the underlying mechanisms in colon cancers. Methods HCT-116, SW480, SW620 and DiFi cells were treated with azithromycin, purified TRAIL, or their combination. A sulforhoddamine B assay was used to examine cell survival. Apoptosis was examined using annexin V-FITC/PI staining, and autophagy was observed by acridine orange staining. Western blot analysis was used to detect protein expression levels. In mechanistic experiments, siRNAs were used to knockdown death receptors (DR4, DR5) and LC-3B. The anticancer effect of azithromycin and TRAIL was also examined in BALB/c nude mice carrying HCT-116 xenografts. Results Azithromycin decreased the proliferation of HCT-116 and SW480 cells in a dose-dependent manner. Combination of azithromycin and TRAIL inhibited tumor growth in a manner that could not be explained by additive effects. Azithromycin increased the expressions of DR4, DR5, p62 and LC-3B proteins and potentiated induction of apoptosis by TRAIL. Knockdown of DR4 and DR5 with siRNAs increased cell survival rate and decreased the expression of cleaved-PARP induced by the combination of azithromycin and TRAIL. LC-3B siRNA and CQ potentiated the anti-proliferation activity of TRAIL alone, and increased the expressions of DR4 and DR5. Conclusion The synergistic antitumor effect of azithromycin and TRAIL mainly relies on the up-regulations of DR4 and DR5, which in turn result from LC-3B-involved autophagy inhibition.

We investigated how the microbiota in the ileum and cecum of broiler chickens fed a diet of low calcium (Ca) and available phosphorus (aP) and prebiotic fructooligosaccharides (FOS) supplements changed over a 3 weeks period. Three dietary treatments were randomly assigned to four replicate cages of five birds each, including: positive control (PC), a wheat-corn-soybean meal-based diet; negative control (NC), as PC with 0.2% reduced Ca and aP; and NC + FOS, as NC supplemented with 0.5% of FOS. Ileal and cecal digesta were sampled from each replicate (n = 4) on d21 and processed for 16S rRNA gene amplicon (V4 region) sequencing using Illumina platform. Statistical differences were observed in the microbiome by GI location as determined by 2-way ANOVA and Permutational MANOVA. On average, 24,216 sequence reads per sample were generated resulting in 800 and 1,280 operational taxonomic units in the ileal and cecal digesta, respectively. Difference (P < 0.0001) on alpha diversity and abundances of several phyla was observed between ileal and cecal digesta. ß-diversity was different (P < 0.05) between each treatment groups in the ileum but not in the cecum. In the cecum, species richness, phylogenetic diversity, and the number of observed species were higher in PC compared to NC + FOS (P < 0.05). Several phyla, including Cyanobacteria, Firmicutes, and Proteobacteria, had significantly different abundance in the ileal and cecal digesta (P < 0.05). In the ileal digesta, positive correlation were observed between Salinibacterium and Lysobacter and PC diet. Blautia, Faecalibacterium and Pseudomonas and the NC diet and Lactobacillus and Escherichia and the NC + FOS diet. In the cecal digesta, Butyrivibrio, and Allobaculum were positively correlated to PC. Although, Clostridium and Anaerotruncus were positively correlated to NC + FOS, they showed negative correlation to PC and NC. The study concludes that dietary Ca and aP level and FOS supplementation alters ileal microbiota of the broiler chickens.