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Background: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections., Methods: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves., Results: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers., Conclusions: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases., (© 2024. The Author(s).)

Carbonized polydopamine (cPDA) exhibits a nitrogenous graphite-like structure with n-type semiconductor property. However, the low electrical conductivity and Seebeck coefficient of cPDA cannot meet the needs of flexible thermoelectric devices. In this study, a series of metal ions were coordinated with cPDA to enhance n-type thermoelectric properties. At 300 K, all metal-coordination cPDA (metal-cPDA) samples obtain lower thermal conductivity compared to cPDA. Mn-cPDA exhibits the greatest Seebeck coefficient of -25.94 μV K -1 , which is almost six times higher than cPDA. Fe-cPDA shows the best electrical conductivity of 2.45 × 10 5 S m -1 . An optimal power factor (PF) value of 11.93 μW m -1 K -2 is achieved in Ca-cPDA with the enhanced electrical conductivity of 9.5 × 10 4 S m -1 and Seebeck coefficient of -11.24 μV K -1 . Using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM), we revealed the structural characterization of metal-cPDA. Our results indictate that the different metal ions (Mn 2+ , Zn 2+ , Mg 2+ , Al 3+ , Ca 2+ , and Fe 3+ ) exert varying influences on the growth of graphite-like structure within metal-cPDA, which lead to the evolution of electrical conductivity. We observe that the carrier density and carrier mobility depend on both the degree of graphitization and the metal-ion coordination, which work together on electrical conductivity and Seebeck coefficient. These findings and understanding of the thermoelectric properties of PDA-based materials will help to realize high-performance n-type thermoelectric materials for flexible electronic device applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin "pioneering factor" GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies revealed that PML::RARA interacts with ~250 proteins in primary mouse hematopoietic cells; GATA2 and 33 others require PML::RARA binding to DNA for the interaction to occur, suggesting that binding to their cognate DNA target motifs may stabilize their interactions. In the absence of PML::RARA , Gata2 overexpression induces many of the same epigenetic and transcriptional changes as PML::RARA . These findings suggested that PML::RARA may indirectly initiate its transcriptional program by activating Gata2 expression: Indeed, we demonstrated that inactivation of Gata2 prior to PML::RARA expression prevented its ability to induce self-renewal. These data suggested that GATA2 binding creates accessible chromatin regions enriched for both GATA and Retinoic Acid Receptor Element motifs, where GATA2 and PML::RARA can potentially bind and interact with each other. In turn, PML::RARA binding to DNA promotes a feed-forward transcriptional program by positively regulating Gata2 expression. Gata2 may therefore be required for PML::RARA to establish its transcriptional program., Competing Interests: Competing interests statement:The authors declare no competing interest.

Oral administration is a convenient drug delivery method in our daily lives. However, it remains a challenge to achieve precise target delivery and ensure the efficacy of medications in extreme environments within the digestive system with complex environments. This paper proposes an oral multilayer magnetic hydrogel microrobot for targeted delivery and on-demand release driven by a gradient magnetic field. The inner hydrogel shells enclose designated drugs and magnetic microparticles. The outer hydrogel shells enclose the inner hydrogel shells, magnetic microparticles, and pH neutralizers. The drug release procedure is remotely implemented layer-by-layer. When the required gradient magnetic field is applied, the outer hydrogel shells are destroyed to release their inclusions. The enclosed pH neutralizers scour the surrounding environment to avoid damaging drugs by the pH environment. Subsequently, the inner hydrogel shells are destroyed to release the drugs. A set of experiments are conducted to demonstrate the wirelessly controllable target delivery and release in a Petri dish and biological tissues. The results demonstrated attractive advantages of the reported microrobot in microcargo delivery with almost no loss, remote controllable release, and drug protection by the pH neutralizers. It is a promising approach to advance next-generation precision oral therapies in the digestive system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xu, Wu, Xu and Xu.)

Background: The utilization of decellularized extracellular matrix has gained considerable attention across numerous areas in regenerative research. Of particular interest is the human articular cartilage-derived extracellular matrix (hACECM), which presents as a promising facilitator for cartilage regeneration. Concurrently, the microfracture (MF) ​technique, a well-established marrow stimulation method, has proven efficacious in the repair of cartilage defects. However, as of the current literature review, no investigations have explored the potential of a combined application of hACECM and the microfracture technique in the repair of cartilage defects within a sheep model., Hypothesis: The combination of hACECM scaffold and microfracture will result in improved repair of full-thickness femoral condyle articular cartilage defects compared to the use of either technique alone., Study Design: Controlled laboratory study., Methods: Full-thickness femoral condyle articular cartilage defect (diameter, 7.0 ​mm; debrided down to the subchondral bone plate) were created in the weight-bearing area of the femoral medial and lateral condyles (n ​= ​24). All of defected sheep were randomly divided into four groups: control, microfracture, hACECM scaffold, and hACECM scaffold ​+ ​microfracture. After 3, 6 and 12 months, the chondral repair was assessed for standardized (semi-) quantitative macroscopic, imaging, histological, immunohistochemical, mechanics, and biochemical analyses in each group., Result: At 3, 6 and 12 months after implantation, the gross view and pathological staining of regenerative tissues were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than in the microfracture and control groups; Micro-CT result showed that the parameters about the calcified layer of cartilage and subchondral bone were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than the others, and excessive subchondral bone proliferation in the microfracture group. The results demonstrate that human cartilage extracellular matrix scaffold alone is an efficient, safe and simple way to repair cartilage defects., Conclusion: hACECM scaffolds combined with/without microfracture facilitate chondral defect repair., The Translational Potential of This Article: Preclinical large animal models represent an important adjunct and surrogate for studies on articular cartilage repair, while the sheep stifle joint reflects many key features of the human knee and are therefore optimal experimental model for future clinical application in human. In this study, we developed a human articular cartilage-derived extracellular matrix scaffold and to verify the viability of its use in sheep animal models. Clinical studies are warranted to further quantify the effects of hACECM scaffolds in similar settings., Competing Interests: All authors involved in this article declare that there are no conflicts of interest regarding the publication of this paper., (© 2023 The Authors.)

Several canonical translocations produce oncofusion genes that can initiate acute myeloid leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase (TurboID) in-frame with 3 favorable-risk AML oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11) and identified their interacting proteins in primary murine hematopoietic cells. The PML::RARA- and RUNX1::RUNX1T1-TurboID fusion proteins labeled common and unique nuclear repressor complexes, implying their nuclear localization. However, CBFB::MYH11-TurboID-interacting proteins were largely cytoplasmic, probably because of an interaction of the MYH11 domain with several cytoplasmic myosin-related proteins. Using a variety of methods, we showed that the CBFB domain of CBFB::MYH11 sequesters RUNX1 in cytoplasmic aggregates; these findings were confirmed in primary human AML cells. Paradoxically, CBFB::MYH11 expression was associated with increased RUNX1/2 expression, suggesting the presence of a sensor for reduced functional RUNX1 protein, and a feedback loop that may attempt to compensate by increasing RUNX1/2 transcription. These findings may have broad implications for AML pathogenesis.

Colorectal cancer (CRC) is one of the most common malignancies, and at the initial visit, most patients are diagnosed with metastatic CRC (mCRC). However, immunotherapy is only and highly effective in a very small proportion of patients with mCRC having mismatch repair defect (dMMR)/high microsatellite instability, and the majority of the patients with mCRC having mismatch repair proficient (pMMR)/microsatellite stability (MSS) cannot benefit from it. At present, many clinical studies of immunotherapy combined with tyrosine kinase inhibitors (TKIs) are trying to regulate the immune microenvironment of pMMR/MSS mCRC, transforming a "cold tumor" into a "hot tumor," which has not only surprising effects but also certain limitations, i.e., the response could not be specific to metastasis. Therefore, regarding the bottleneck encountered by immunotherapy in patients with patients pMMR/MSS mCRC, this study summarized current research and possible mechanisms of immunotherapy combined with local therapy for metastasis, including radiotherapy, ablation, and transcatheter arterial chemoembolization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). The hypomethylating agent azacitidine (AZA) has been shown to be effective in preclinical and clinical studies for the prevention of acute GVHD (aGVHD). We sought to determine the maximum tolerated dose (MTD) of AZA when given on days 1 to 5 of a 28-day cycle for 4 cycles, starting on day +7 after allo-HCT, as well as its impact on aGVHD and chronic GVHD (cGVHD), relapse, and overall survival (OS) in patients undergoing matched unrelated donor allo-HCT. This study was a single-arm, single-center, open-label phase I-II study with a total of 15 and 38 patients enrolled in the phase I and II portions of the trial, respectively. A standard 3+3 study design was used in phase I, and all patients in phase II received AZA at the MTD determined in phase I. The MTD of AZA starting at day +7 post-transplantation was 45 mg/m 2 . Phase II of the study was halted after enrolling 38 of the planned 46 patients following an interim analysis that suggested futility. Overall, AZA at 45 mg/m 2 exhibited a side effect profile consistent with prior reports and had a minimal impact on engraftment. The cumulative incidence of clinically significant aGVHD by day +180 was 39.9% (95% confidence interval [CI], 22% to 53.7%). The incidence of all-grade cGVHD was 61.4% (95% CI, 40.3% to 75%). At 1 year, OS was 73.7% (95% CI, 60.9% to 89.1%), and the disease relapse rate was 11.4% (95% CI, .2% to 21.3%). Our results suggest that early post-allo-HCT AZA has limited efficacy in preventing aGVHD and cGVHD but could have a beneficial effect in preventing disease relapse., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post-traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell-mediated tissue repair may be achieved., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The study explored the biofilm (BF) formation capacity, BF-related gene profiles, and the trends in antimicrobial resistance (AMR) of Salmonella pullorum (SP) strains over several years. A total of 627 SP strains were isolated from 4,540 samples collected from chicken farms in Guangxi, China during 2018-2022. The BF-forming capacity of these isolates was assessed using crystal violet staining, and the presence of eight BF-related genes ( csgA, csgB, csgD, ompR, bapA, pfs, luxS , and rpoS ) in BF formation-positive strains was determined through Polymerase Chain Reaction (PCR) analysis. Antimicrobial susceptibility test was conducted to investigate the AMR of the isolates. Minimum Inhibitory Concentration (MIC) and Minimal Biofilm Eradication Concentration (MBEC) of nine SP-BF strains were determined using the broth microdilution method to assess the impact of BF formation on AMR. Additionally, the Optimal Biofilm Formation Conditions (OBFC) were investigated. The results indicated that 36.8% (231/627) of the strains exhibited a positive BF-formation capacity. Among these, 24.7% (57/231) were strong BF producers, 23.4% (54/231) were moderate BF producers, and 51.9% (120/231) were weak BF producers. Analysis of the eight BF-related genes in SP-BF strains revealed that over 90% of them were positive for all the genes. Antimicrobial susceptibility test conducted on the isolates showed that 100% (231/231) of them exhibited resistance to at least one antibiotic, with 98.3% (227/231) demonstrating multidrug resistance (MDR). Both MIC and MBEC measurements indicated varying degrees of increased AMR after BF formation of the bacteria. The optimal conditions for BF formation were observed at 37°C after 48 h of incubation, with an initial bacterial concentration of 1.2 × 10 6 CFU/mL. Notably, NaCl had a significant inhibitory effect on BF formation, while glucose and Trypticase Soy Broth (TSB) positively influenced BF formation. The results of the study emphasized the need for effective preventive and control strategies to address the challenges posed by the BF formation and MDR of SP in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Xu, Li, Wang, Wang, Liang and Wei.)

Note that images of low-illumination are weak aperiodic signals, while mutual information can be used as an effective measure for the shared information between the input stimulus and the output response of nonlinear systems, thus it is possible to develop novel visual perception algorithm based on the principle of aperiodic stochastic resonance within the frame of information theory. To confirm this, we reveal this phenomenon using the integrate-and-fire neural networks of neurons with noisy binary random signal as input first. And then, we propose an improved visual perception algorithm with the image mutual information as assessment index. The numerical experiences show that the target image can be picked up with more easiness by the maximal mutual information than by the minimum of natural image quality evaluation (NIQE), which is one of the most frequently used indexes. Moreover, the advantage of choosing quantile as spike threshold has also been confirmed. The improvement of this research should provide large convenience for potential applications including video tracking in environments of low illumination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Zhai and Kang.)

Background: Coagulation disorders are a significant cause of lung cancer mortality. Although mast cells are known to play a role in coagulation abnormalities, their specific role in this process has not yet been elucidated., Method: We detected mast cells in the tumor microenvironment using single-cell sequencing data and examined their correlation with thrombosis-related genes, neutrophil-related genes, neutrophil extracellular trap-related signature genes, and immune infiltration levels in lung cancer patients through bioinformatics analysis. Bone marrow mast cell uptake of exosomes isolated from the lung adenocarcinoma cell line A549, which were labeled using PKH67, was observed using confocal microscopy. Mast cell degranulation was detected by measuring the β-hexosaminidase release rate. Additionally, cytokine array analysis was performed to identify altered mediators released by bone marrow mast cells after uptake of the exosomes., Results: In our study, we found a close correlation between the proportion of mast cells in lung cancer patients and the expression levels of thrombosis-related genes and neutrophil extracellular trap signature genes, both of which play a key role in thrombophilic disorder. Moreover, we discovered that lung cancer cell-derived exosomes can be taken up by mast cells, which in turn become activated to release procoagulant mediators., Conclusion: Our study shows that exosomes derived from lung cancer cells can activate mast cells to release procoagulants that may contribute to abnormal blood clotting in lung cancer patients. Video Abstract., (© 2023. The Author(s).)

Hepatitis E is a disease of public health significance caused by the cross-species transmission of zoonotic hepatitis E virus (HEV) infection. There are no specific drugs. In this study, network pharmacology was used to reveal the mechanism of treatment of the active constituents of the Abrus cantoniensis Hance on hepatitis E. Based on the previously published representative components of A. cantoniensis Hance, we were screened the active components with OB ≥ 20% and DL ≥ 0.1 in A. cantoniensis Hance based on the TCMSP, predicted the target online through Swiss target prediction, and integrated the hepatitis E target in the GeneCards and DisGenet databases. Then, the core target was screened and the GO and KEGG enrichment and the network of the drug-active-ingredient-disease-pathway-target analysis were performed by the Cytoscape software. There were 11,046 hepatitis E targets, including PI3K-AKt, SRC, MAPK, PTPN11, EGFR, STAT1 and so on. The core ingredients include Oleanolic acid, Butin, β-sitosterol, Soyasapogenol E, 5,7-dihydroxy-2-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one, Stigmasterol, Emodin, Physcion, and Enoxolone. A total of 1,410 GO enrichment results of core targets, including 1,246 biological process, 51 cell composition and 113 molecular function results. KEGG pathway was enriched in 150 related pathways, suggesting that A. cantoniensis Hance acts on cancer signaling pathway, endocrine resistance pathway, PI3K-AKt signaling pathway, MAPK, TNF and other signaling pathway. Through key components such as Oleanolic acid, Butin, β-sitosterol, Stigmasterol, and Enoxolone and other components interferes with AKT1, IL-6 and TNF, and regulates pathway in cancer, PI3K-AKt signaling pathway and MAPK pathway to play a therapeutic role in hepatitis E., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Wang, Luan, Zhang and Dong.)

The Chinese traditional medicinal plants Rheum palmatum L., Scutellaria baicalensis Georgi , and Houttuynia cordata Thunb in a ratio of 108:65:27 form a compound named Dahuang Qinyu San (DQS), which inhibits and kills Escherichia coli and Salmonella to a certain extent in fish and shrimp aquaculture environments. The active ingredients quercetin, emodin, baicalin, and aloe-emodin are obtained from the semi-biomimetic extract of DQS (SEDQS). However, the antibacterial mechanism of SEDQS against Salmonella is still unclear. This study used the microwell-plate method to determine the Minimum Inhibitory Concentration (MIC) of SEDQS against Salmonella enteritidis ( S. enteritidis ) isolated from geese. In addition, the effect of SEDQS on the growth curve, respiratory metabolic system, cell wall, soluble protein, and nucleic acid in bacterial liquid of S. enteritidis was detected by spectrophotometer and reagent kit. The effects of SEDQS on S. enteritidis DNA, binding gel blocking, virulence gene expression, and pathogenicity-related proteins were determined by gel electrophoresis, SDS-PAGE, and fluorescence quantitative PCR. The study found that a concentration of 1/4 MIC-2 MIC (2.27-18.2 mg/ml) SEDQS can significantly inhibit the normal growth of S. enteritidis , destroy the cell membrane structure of bacteria resulting in the leak of nucleic acid, protein, and other contents ( P < 0.01). It also significantly inhibited the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH; P < 0.01) in a concentration-dependent manner. When the concentration of SEDQS was 1/2 MIC to 2 MIC (4.55-18.2 mg/ml), the expression levels of gyrB, fimA, filC, spvR, Hcp , and vgrG virulence genes ( P < 0.01) all decreased by more than 31, 11, 18, 30, 34, and 21% respectively compared with the control group. SEDQS could significantly inhibit the expression of six virulence genes and play an important role in the pathogenicity of the S. enteritidis infected host. The SEDQS could exert antibacterial pharmacological effects by inhibiting the growth and metabolism of S. enteritidis and inhibiting the expression of major virulence factors. It has potential application value as an antibiotic alternative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Bai, Xu, Sun, Françoise, Luan and Wang.)

In order to prevent pullorum disease and fowl typhoid in breeders, the use of oregano essential oil (OEO) was tested for the prevention and treatment of infections of multidrug-resistant Salmonella pullorum (SP) and Salmonella gallinarum (SG) in commercial Yellow-chicken breeders. In the challenge-protection experiment, commercial Hongguang-Black 1-day-old breeder chicks were randomly divided into four groups, including A (challenged, preventive dose), B (challenged, treatment dose), C (challenged, untreated), and D (unchallenged, untreated). Group A was supplemented with 200 μL/L OEO in the drinking water during the whole trial (1-35 days of age) and group B was supplemented with 400 μL/L OEO during 8-12 days of age, while groups C and D were kept as untreated controls. At 7 days of age, birds of groups A, B, and C were divided into two subgroups with equal number of birds (A 1 -A 2 , B 1 -B 2 , and C 1 -C 2 ), and then subgroups A 1 , B 1 , and C 1 were challenged with SP, while subgroups A 2 , B 2 , and C 2 were challenged with SG. Clinical symptoms and death were observed and recorded daily. Every week during the experiment, serum antibodies against SP and SG of all the groups were detected by the plate agglutinate test (PAT). At the age of 35 days, all birds were weighed and necropsied, lesions were recorded and the challenging pathogens were isolated. The results showed that the positive rates of SP and SG isolation in groups A 1 , A 2 and B 1 , B 2 were significantly lower ( P < 0.05) than those of groups C 1 and C 2 , respectively, while groups A 1 and A 2 were slightly lower ( P > 0.05) than those of groups B 1 and B 2 . The average body weight (BW) of groups A 1 and A 2 were significantly higher ( P < 0.05) than those of groups B 1 , B 2 and C 1 , C 2 , respectively, but there was no significant difference ( P > 0.05) with that of group D. The r -value between PAT positive and the recovery rates of Salmonella was 0.99, which means they are highly positively correlated. The results of this study demonstrated that the prevention dose (200μL/L) and the treatment dose (400 μL/L) of OEO supplemented in the drinking water could all effectively decrease infections of SP and SG and that the effect of the prevention was greater than that of the treatment and finally that the prevention could also significantly reduce the BW decline of birds challenged with SP and SG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Wang, Li, Wang, Chen, Zhou and Wei.)

Salmonella is capable of harming human and animal health, and its multidrug resistance (MDR) has always been a public health problem. In addition, antibiotic-free or antibiotic-reduced policies have been implemented in poultry production. Therefore, the search for antibiotic alternatives is more urgent than ever before. The aim of this study was to assess the antibacterial activity of star anise-cinnamon essential oil (SCEO) in vitro and its prophylactic effect against the infections of Salmonella pullorum , Salmonella give , and Salmonella kentucky in vivo. The results demonstrated that SCEO is effective against Salmonella pullorum , Salmonella give , and Salmonella kentucky in vitro. Supplementation with SCEO could significantly decrease the infections of Salmonella pullorum and Salmonella give , whereas it could slightly but not significantly decrease the infection of Salmonella kentucky , while also significantly alleviating the body weight (BW) loss caused by the infections of Salmonella pullorum , Salmonella give , and Salmonella kentucky in Yellow chickens. The SCEO had the best prophylactic effect against the infection of Salmonella give in Yellow chickens, followed by the infection of Salmonella pullorum and the infection of Salmonella kentucky . The SCEO, used as an antibiotic alternative, could be an effective prevention strategy against the infections of Salmonella pullorum , Salmonella give , and Salmonella kentucky in Yellow chickens.

We have developed a deep-scale proteome and phosphoproteome database from 44 representative acute myeloid leukemia (AML) patients from the LAML TCGA dataset and 6 healthy bone marrow-derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. We identified examples of posttranscriptionally regulated proteins both globally (ie, in all AML samples) and also in patients with recurrent AML driver mutations. For example, samples with IDH1/2 mutations displayed elevated levels of the 2-oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in messenger RNA levels for these genes; we confirmed this finding in vitro. In samples with NPMc mutations, we identified several nuclear importins with posttranscriptionally increased protein abundance and showed that they interact with NPMc but not wild-type NPM1. We identified 2 cell surface proteins (CD180 and MRC1/CD206) expressed on AML blasts of many patients (but not healthy CD34+ stem/progenitor cells) that could represent novel targets for immunologic therapies and confirmed these targets via flow cytometry. Finally, we detected nearly 30 000 phosphosites in these samples; globally, AML samples were associated with the abnormal phosphorylation of specific residues in PTPN11, STAT3, AKT1, and PRKCD. FLT3-TKD samples were associated with increased phosphorylation of activating tyrosines on the cytoplasmic Src-family tyrosine kinases FGR and HCK and related signaling proteins. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis., (© 2022 by The American Society of Hematology.)

Enzyme-free DNA amplifiers can amplify the signal of nucleic acid molecules. They can be applied to DNA molecular operation and nucleic acid detection. The reaction speed is the core index to evaluate DNA amplifiers. In this study, we designed a DNA amplifier based on an enzyme-free chain reaction. This DNA amplifier can release one more signal molecule in each round of reaction and trigger the next round, which significantly improved reaction speed. Moreover, because the amplifier used a stable DNA structure, the reaction can occur at room temperature. To integrate the amplifier into other DNA molecular operations, we performed the amplification reaction in a microfluidic chip module. The results showed that the amplifier can realize real-time signal feedback at a proper input molecule concentration and reach the endpoint in 40 s, even at a low relative concentration. To apply the amplifier for nucleic acid detection, we also used a conventional fluorescent polymerase chain reaction instrument for the reaction. The results showed that the amplifier specifically detected trace DNA single-stranded molecules. To solve the leakage problem of existing amplifiers, we designed a DNA molecule as the chain reaction's inhibitor, which was crucial in controlling the reaction speed and preventing leakage. STATEMENT OF SIGNIFICANCE: Traditional amplifier strategies of enzyme-free DNA amplifiers relied on a constant number of cycling molecules to catalyze the amplifier molecules' changing structure and release fluorescent signals, which lead low reaction speed. Based on an enzyme-free chain reaction, we designed a DNA amplifier which can release one more cycling molecule in each loop and trigger the next loop and significantly improve reaction speed in this study. Our analysis on microfluidic chip module and PCR instrument verifies high sensitivity and selectivity. And this strategy of DNA amplifier realizes the control of reaction and prevents leakage. We believe that this automated amplification strategy could have great applications in vivo signal detection, imaging, and signal molecule translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known computing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Meadow soil is a vital ecosystem component and can be influenced by meadow vegetation. Evaluating soil quality in mountain meadows subjected to different levels of tourism disturbance is essential for scientific research, ecological restoration, and sustainable management. This study aimed to evaluate meadow soil quality at different tourism-disturbance levels and attempted to establish a minimum data set (MDS) with compatible indicators for soil quality assessment of subtropical mountain meadows. We analyzed fifteen soil physical, chemical, and biological indicators in control check (CK), light disturbance (LD), medium disturbance (MD), and severe disturbance (SD) meadow areas in Wugong Mountain, west of Jiangxi, China. In addition, a soil quality index (SQI) was determined using the established MDS based on the integrated soil quality index. Average soil permeability, soil pH, available nitrogen (AN), available phosphorus (AP), and number of fungal OTUs were finally introduced into the MDS to evaluate meadow soil quality at different tourism-disturbance levels. The study found that the soil of the Wugong Mountain meadow was acidic, the bulk density was loose, and the nutrient content was rich. Additionally, SQI decreased with increase in tourism-disturbance level. The mean SQI values of the Wugong Mountain meadow areas were: CK, 0.612; LD, 0.493; MD, 0.448; and SD, 0.416. Our results demonstrate that the SQI based on the MDS method could be a valuable tool with which to indicate the soil quality of mountain meadow areas, and the SQI can be regarded as a primary indicator of ecological restoration and sustainable management.

This paper presents the design and optimization of a new alternating electromagnetic-field-generation system, which is dedicated to actuating untethered magnetic microrobots under an inverted microscope. Its uniqueness is that the system parameters are optimally designed by considering both electric and geometry constraints for the target-driving application. The dominant parameters of the system are first determined by establishing analytical models. According to the requirements of targeted application, the optimization problem with certain constraints is formulated, which is solved via the multiobjective genetic algorithm method. A prototype system with the optimal parameters is developed for experimental testing. Experimental studies are carried out to characterize actual performance of the developed actuation system. For demonstration, a magnetic microball has been actuated for navigation by surface rolling in a petri dish filled with pure water. Results indicate that the reported electromagnetic-field-generation system meets the actuation requirements for potential applications.

DNA logic gates, nanocomputing circuits, have already implemented basic computations and shown great signal potential for nano logic material application. However, the reaction temperature and computing speed still limit its development. Performing complicated computations requires a more stable component and a better computing platform. We proposed a more stable design of logic gates based on a triple, double-stranded, DNA (T-dsDNA) structure. We demonstrated a half adder and a full adder using these DNA nanocircuits and performed the computations in a microfluidic chip device at room temperature. When the solutions were mixed in the device, we obtained the expected results in real time, which suggested that the T-dsDNA combined microfluidic chip provides a concise strategy for large DNA nanocircuits.

Abstract: Salmonella is one of the major pathogenic bacteria causing foodborne diseases. The rapid detection of Salmonella in food is of great significance to food safety. In this study, the loop-mediated isothermal amplification (LAMP) method was developed, and primers were designed targeting the invA gene of Salmonella. Standard samples of recombinant invA-plasmid and 100 retail meat samples were tested by LAMP and compared with the results tested by conventional PCR and the routine Chinese National Food Safety Standard-Microbiological Examination of Food-Examination of Salmonella, respectively. The results showed that Salmonella strains of eight different serotypes were amplified successfully by the developed LAMP assay, and it was 1,000-fold more sensitive than conventional PCR, with the analytical sensitivity of 8 × 102 copies per μL of the standard sample of invA-plasmid. The results were visualized directly by adding calcein and MnCl2 in the LAMP reaction tube, and the positively amplified products turned green after an incubation of 2 min. In parallel detection, the positive rate of Salmonella by the LAMP assay was highly correlated with the routine Chinese national standard method. The results of the study demonstrated that the developed LAMP assay is a simple, rapid, strongly specific, highly sensitive, and visual detection method for Salmonella., (Copyright ©, International Association for Food Protection.)

To better understand clonal and transcriptional adaptations after relapse in patients with acute myeloid leukemia (AML), we collected presentation and relapse samples from six normal karyotype AML cases. We performed enhanced whole-genome sequencing to characterize clonal evolution, and deep-coverage single-cell RNA sequencing on the same samples, which yielded 142,642 high-quality cells for analysis. Identifying expressed mutations in individual cells enabled us to discriminate between normal and AML cells, to identify coordinated changes in the genome and transcriptome, and to identify subclone-specific cell states. We quantified the coevolution of genetic and transcriptional heterogeneity during AML progression, and found that transcriptional changes were significantly correlated with genetic changes. However, transcriptional adaptation sometimes occurred independently, suggesting that clonal evolution does not represent all relevant biological changes. In three cases, we identified cells at diagnosis that likely seeded the relapse. Finally, these data revealed a conserved relapse-enriched leukemic cell state bearing markers of stemness, quiescence, and adhesion. SIGNIFICANCE: These data enabled us to identify a relapse-enriched leukemic cell state with distinct transcriptional properties. Detailed case-by-case analyses elucidated the complex ways in which the AML genome, transcriptome, and immune microenvironment interact to evade chemotherapy. These analyses provide a blueprint for evaluating these factors in larger cohorts. This article is highlighted in the In This Issue feature, p. 1 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Sepsis is a frequent cause of kidney injury. The present study investigated whether Alamandine (Ala) could alleviate sepsis-associated renal injury by reducing inflammation and apoptosis. In addition, we investigated downstream signaling pathways modulated by Ala. Studies were performed in mice treated with lipopolysaccharide (LPS) and in the human proximal tubular epithelial cell line HK-2. The increase in serum creatinine, blood urea nitrogen, cystatin C and Fg, and neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in the kidneys of mice treated with LPS were reduced after administration of Ala. Exposure to LPS increased interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) in mice and HK-2 cells, but were reduced after Ala treatment. Furthermore, increased levels of cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, cleaved poly (ADP-ribose) polymerase (PARP) and Bax and reduced levels of Bcl2 in LPS-treated mice and HK-2 cells were reversed after Ala administration. In addition, LPS increased the levels of p-PI3K/PI3K, p-Akt/Akt, p-ERK/ERK, p-JNK/JNK, p-p38/p38 and p-FoxO1 in HK-2 cells, and all were reversed after Ala administration. These results indicate that Ala could improve renal function and inhibit inflammation and apoptosis in LPS induced sepsis mouse models. We demonstrated that Ala attenuated LPS induced sepsis by inhibiting the PI3K/Akt and MAPK signaling pathways., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Staphylococcus aureus ( S. aureus ) biofilm plays an important role in the persistence of chronic infection due to its resistance to antibiotics. Because of their functional diversity, active polysaccharide is increasingly being applied as a biocontrol agent to inhibit the formation of biofilm by pathogens. In this study, a new polysaccharide, GBSPII-1, isolated from the fresh sarcotesta of Ginkgo biloba L . ( G. biloba ) was characterized and its effect on antibiofilm formation of S. aureus was examined in vitro . High-Performance Liquid Chromatography (HPLC) analysis showed that GBSPII-1 is an acidic heteropolysaccharide composed of mannose, rhamnose, glucose, glucuronic acid, and galacturonic acid. GBSPII-1 demonstrated a molecular weight of 34 kDa and may affect the accumulation of polysaccharide intercellular adhesion (PIA) by inhibiting ica A, ica B, ica C, and ica D gene expression at subinhibitory concentrations. Under 10 g/L, GBSPII-1 showed an antioxidant effect on the inhibition rate of H 2 O 2 -induced erythrocyte hemolysis and the scavenging rate of DPPH radicals was 76.5 ± 0.5% and 89.2 ± 0.26%, respectively. The findings obtained in this study indicate that GBSPII-1 has antibacterial effect, is a possible source of natural antioxidants, and may be a potential biocontrol agent for the design of new therapeutic strategies for biofilm-related S. aureus infections., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Hong Jiang et al.)

To maintain the beneficial effects of microbial inoculants on plants and soil, repeated inoculation represents a promising option. Until now, the impacts of one-off inoculation on the native microbiome have been explored, but it remains unclear how long and to what extent the periodic inoculations would affect the succession of the resident microbiome in bulk soil. Here, we examined the dynamic responses of plant growth, soil functions, and the resident bacterial community in the bulk soil to periodic inoculations of phosphate-solubilizing and N 2 -fixing bacteria alone or in combination. Compared to single-strain inoculation, coinoculation better stimulated plant growth and soil nutrients. However, the benefits from inoculants did not increase with repeated inoculations and were not maintained after transplantation to a different site. In response to microbial inoculants, three patterns of shifts in the bacterial composition were observed: fold increase, fold decrease, and resilience. The periodic inoculations impacted the succession course of resident bacterial communities in bulk soil, mainly driven by changes in soil pH and nitrate, resulting in the development of three main cluster types throughout the investigation. The single and mixed inoculants transiently modulated the variation in the resident community in association with soil pH and the C/N ratio, but finally, the community established and showed resilience to subsequent inoculations. Consequently, the necessity of repeated inoculations should be reconsidered, and while the different microbial inoculants showed distinct impacts on resident microbiome succession, the communities ultimately exhibited resilience. IMPORTANCE Introducing beneficial microbes to the plant-soil system is an environmentally friendly approach to improve the crop yield and soil environment. Numerous studies have attempted to reveal the impacts of inoculation on the rhizosphere microbiome. However, little is known about the effectiveness of periodic inoculations on soil functioning. In addition, the long-term impact of repeated inoculations on the native community remains unclear. Here, we track the succession traits of the resident microbiome in the bulk soil across a growing season and identify the taxon clusters that respond differently to periodic inoculation. Crucially, we compare the development of the resident community composition with and without inoculation, thus providing new insight into the interactions between resident microbes and intruders. Finally, we conclude that initial inoculation plays a more important role in influencing the whole system, and the native microbial community exhibits traits of resilience, but no resistance, to the subsequent inoculations., (Copyright © 2021 Wang et al.)

Salmonella, one of the most important foodborne pathogens, can be the cause of bacterial food-borne illness and is commonly associated with the consumption of retail meat. Multidrug-resistant Salmonella isolates with high adaptability, have been responsible for many foodborne disease outbreaks. Here we present an investigation on the contamination and the antimicrobial resistance of Salmonella in retail meat obtained from supermarkets and from open markets in Guangxi, China. From the years 2009 to 2016, a total of 604 Salmonella isolates were recovered from a total of 3340 meat samples including 797 beef, 911 pork, 942 chicken and 690 duck, representing 18.08% of the samples tested. Pork was the most contaminated meat. Salmonella was detected in 322 samples from supermarkets and the positive rate of 21.03% was higher than that of 15.70% in 284 samples from open markets (P<0.05). The prevalence of Salmonella in retail meat in the summer and fall months: June (2015, 40.63%), October (2012, 34.6%; 2016, 43.75%) was higher than in other seasons of the year. One hundred and twenty-seven serotypes were identified among the 604 Salmonella enterica isolates, and S. Derby (28.48%), S. Agona (9.77%), S. London (4.97%) and S. Enteritidis (4.47%) were the most common serotypes. Tests of susceptibility to 21 antimicrobial agents showed that 87.58% of the isolates were resistant to at least one antimicrobial, and 57.79% exhibited multidrug resistance (MDR), as they were resistant to at least three antimicrobials. The presence of most of the antimicrobial-resistant genes tested was consistent with the resistant phenotypes found. Among all the antimicrobial resistant genes (ARGs) examined in this study, bla TEM-1 , aadA1, cmlA, tetA, sul1 and sul2 were the most prevalent resistant genes in the multidrug resistant isolates. Our findings show that there was a trend that the Salmonella contamination in retail meat had increased and isolates showed an MDR phenotype and that the MDR had become more and more serious. Twenty-one isolates of S. Agona were randomly analyzed by using the enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) and six different types were found, indicating the existence of cross-contamination in the food market. The results indicate that the hazard analysis of the critical control points (HACCP) system for the whole food chain of retail meat should be further analyzed and improved., Competing Interests: Declaration of competing interest No potential conflict of interest was declared by the all authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction : Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib. Areas covered : The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed. Expert opinion : There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future.

Response surface methodology and central composite design based on single-factor experiments were used to optimize the extraction parameters (i.e., extraction time, extraction temperature, and solid-liquid ratio) of polysaccharides from the testa of Salicornia herbacea (STP). The optimal conditions included a liquid-solid ratio of 57:1 (volume/mass), an extraction time of 300min and an extraction temperature of 87°C. Under these conditions, the maximal yield of crude STP was 1.30±0.06%, which agreed with model predictions. Preliminary characterization of the purified acidic polysaccharide (STP II-1) by high performance liquid chromatography indicated that it was composed mainly of d-mannose, d-rhamnose, d-glucose, d-galactose, d-arabinose, glucuronic acid and galacturonic acid. The antioxidant capacity of STP II-1 was analyzed by monitoring both the scavenging rate of the 2,2-diphenyl-1-picrylhydrazyl free radical and inhibition rate of H 2 O 2 -induced erythrocyte hemolysis., (Copyright © 2017. Published by Elsevier Ltd.)

Pregnancy complications including pre-eclampsia, gestational-diabetes mellitus, preterm birth and intrauterine growth restriction can cause acute and chronic health problems for the mother and lead to fetal loss or dysregulation of infant physiology. The human placenta is susceptible to oxidative stress and oxidative damage in early gestation contributes to the onset of these conditions later in pregnancy. Current methods of predicting pregnancy complications are limited and although a large number of factors are associated with disease progression, few biomarkers have been used to aid in disease diagnosis early in gestation. This review discusses the detection of oxidative stress markers in biological fluids and highlights the need for further studies to validate their use in the prediction or diagnosis of pregnancy disorders.

In eukaryotic cells, cell migration is a dynamic and complex process that involves finely tuned orchestration of a multitude of proteins including, for example, those involved in focal adhesions (FAs). Cell migration plays an indispensable role in particular stages of development and its proper regulation is crucial in various biological processes, from wound healing to the immune response. FAs are transmembrane protein complexes that traverse cytoskeletal infrastructures all the way to the extracellular matrix, producing traction at the leading edge of the cell, thus allowing for motility. The assembly of FAs has been extensively studied, whereas disassembly remains poorly understood. Here, we highlight 2 recent studies (see the corresponding puncta in the previous and current issues of the journal) that demonstrate a requirement for macroautophagy/autophagy in FA disassembly. These studies also provide a deeper understanding of how autophagy can contribute to cell migration among multiple cell types.

Autophagy is a pathway mediating vacuolar degradation and recycling of proteins and organelles, which plays crucial roles in cellular physiology. To ensure its proper cytoprotective function, the induction and amplitude of autophagy are tightly regulated, and defects in its regulation are associated with various diseases. Transcriptional control of autophagy is a critical aspect of autophagy regulation, which remains largely unexplored. In particular, very few transcription factors involved in the activation or repression of autophagy-related gene expression have been characterized. To identify such regulators, we analyzed the expression of representative ATG genes in a large collection of DNA-binding mutant deletion strains in growing conditions as well as after nitrogen or glucose starvation. This analysis identified several proteins involved in the transcriptional control of ATG genes. Further analyses showed a correlation between variations in expression and autophagy magnitude, thus identifying new positive and negative regulators of the autophagy pathway. By providing a detailed analysis of the regulatory network of the ATG genes our study paves the way for future research on autophagy regulation and signaling.