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The characterization of a biosimilar drug HS016, the reference product adalimumab (Humira), and their biosimilarities were determined using physical chemistry and functional similarity tests. The primary and higher order structures, size and charge variants, glycosylation profiles, and in vitro potency of both antibodies were characterized both for unstressed and stability samples. Slight differences were observed in the relative levels of methionine oxidation, low molecular weight components, terminal lysine variant, high mannoses and galactosylated glycans between HS016 and Humira. However, no differences in antigen binding activity, Fc receptor affinity, antibody-dependent cell-mediated cytotoxicity or complemented-dependent cytotoxicity were found. The primary and higher order structures, physicochemical properties, and biological activity of HS016 and adalimumab were similar.

Cholesterol crystals participate in cholesterol nucleation; however, the role of cholesterol crystals in gallstone development is unknown. Mucin secretion contributes to increased size of gallstones. Cholesterol crystals activate inflammasomes and participate in many sterile inflammation related human diseases. We investigated the role of cholesterol crystals and mucins in sterile inflammation and gallstone enlargement. We found that expression of mucin 5AC (MUC5AC), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and interleukin-1b (IL-1b) was increased significantly in tissues adjacent to gallstones. Experiments in vitro showed that cholesterol crystals promote MUC5AC secretion; they also increase expression of NLRP3, NLR family CARD domain-containing 4 (NLRC4), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and cleaved caspase-1 in biliary epithelial cells. Inhibition of Inflammasomes by NLRP3, ASC or caspase-1 small interfering RNAs reduced MUC5AC secretion. Also, the IL-1 receptor antagonist, IL1RA, and caspase-1 inhibitor, Ac-YVAD, both inhibited MUC5AC secretion induced by cholesterol crystals. We found that inflammasome activation participates in cholesterol crystal induced mucin secretion and gallstone development.

Pollination niche shifts can drive remarkable floral divergence between closely related plant species. The Leucolirion clade of Lilium contains species with either tepal-recurved or trumpet-shaped flowers. The tepal-recurved flowers are bright orange and might be pollinated by butterflies and/or birds. The trumpet-shaped flowers are mostly pale and strongly fragrant and might permit visitation by a variety of hawkmoths. Lilium leucanthum has trumpet-shaped flowers, and some populations of this species show dark coloration on the floral outer surface, suggesting pollination by mammals. We identified pollinators and examined the dependence of reproduction on pollinators by floral visitor observations, pollen load analysis and pollination experiments. We also analysed floral traits to contrast the two floral syndromes involving different lepidopteran groups. The tepal-recurved lilies are specialized on a group of Papilio butterflies for pollination with pollen predominantly attached to the hindwings. The trumpet-shaped flowers are almost exclusively pollinated by hawkmoths, including diverse species with proboscises of different lengths. No mammal visitation was found to the populations of L. leucanthum with dark outer surfaces of flowers. Self-incompatibility prevails throughout the clade, including the populations in which pollinators were scarce. The butterfly- and hawkmoth-pollinated species display contrasting floral syndromes. Our findings confirmed that the dichotomy in floral syndrome in the Leucolirion clade is associated with Papilio butterfly vs. hawkmoth pollination, whereas intraspecific variation in colour of the floral outer surface of L. leucanthum many need a non-pollinator explanation.

N-glycosylation starts with the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER). Alg2 mannosyltransferase adds both the α1,3- and α1,6-mannose (Man) onto ManGlcNAc2-pyrophosphate-dolichol (M1Gn2-PDol) in either order to generate the branched M3Gn2-PDol product. The well-studied yeast Alg2 interacts with ER membrane through four hydrophobic domains. Unexpectedly, we show that Alg2 structure has diverged between yeast and humans. Human Alg2 (hAlg2) associates with the ER via a single membrane-binding domain and is markedly more stable in vitro. These properties were exploited to develop a liquid chromatography-mass spectrometry quantitative kinetics assay for studying purified hAlg2. Under physiological conditions, hAlg2 prefers to transfer α1,3-Man onto M1Gn2 before adding the α1,6-Man. However, this bias is altered by an excess of GDP-Man donor or an increased level of M1Gn2 substrate, both of which trigger production of the M2Gn2(α-1,6)-PDol. These results suggest that Alg2 may regulate the LLO biosynthetic pathway by controlling accumulation of M2Gn2 (α-1,6) intermediate.

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an evolving global health crisis. Currently, a number of risk factors have been identified to have a potential impact on increasing the morbidity of COVID-19 in adults, including old age, male sex, pre-existing comorbidities, and racial/ethnic disparities. In addition to these factors, changes in laboratory indices and pro-inflammatory cytokines, as well as possible complications, could indicate the progression of COVID-19 into a severe and critical stage. Children predominantly suffer from mild illnesses due to COVID-19. Similar to adults, the main risk factors in pediatric patients include age and pre-existing comorbidities. In contrast, supplementation with a healthy diet and sufficient nutrition, COVID-19 vaccination, and atopic conditions may act as protective factors against the infection of SARS-CoV-2. COVID-19 vaccination not only protects vulnerable individuals from SARS-CoV-2 infection, more importantly, it may also reduce the development of severe disease and death due to COVID-19. Currently used therapies for COVID-19 are off-label and empiric, and their impacts on the severity and mortality of COVID-19 are still unclear. The interaction between asthma and COVID-19 may be bidirectional and needs to be clarified in more studies. In this review, we highlight the clinical evidence supporting the rationale for the risk and protective factors for the morbidity, severity, and mortality of COVID-19.

Determinism and stochasticity in microbial community composition decisions have attracted wide attention. However, there is no consensus on their interrelationships and relative importance, and the mechanism controlling the interaction between the two ecological processes remains to be revealed. The interaction of the two ecological processes on the continental shelf of the South China Sea was studied by performing 16S rRNA gene amplicon sequencing on 90 sediments at multiple depths in five sites. Three nearshore sites have higher microbial diversity than those two close to the shelf margin. Different microbial composition was observed between sites and microbial composition of nearshore sites was positively correlated with total nitrogen, total sulfur, total organic carbon, and dissolved oxygen, while that of offshore was positively correlated with total carbon, salinity, and photosynthetically active radiation. The null model test showed that the community composition among layers of the same site and between nearby sites was mainly dominated by the homogeneous selection, while that between distant sites was mainly affected by dispersal limitation, which indicates that geographic scale influences the interactivities of determinism and stochasticity. Our research indicates that the balance of these two ecological processes along the geographic scale is mainly determined by the dispersal ability of microbes and environmental heterogeneity between areas. The study provides new insights into how deterministic and stochastic processes shape microbial community composition on the continental shelf.

Helicobacter pylori (H. pylori) is the most common risk factor for gastric cancer worldwide. The membrane proteins of the H. pylori are involved in bacterial adherence and play a vital role in the field of drug discovery. Thus, an accurate and cost-effective computational model is needed to predict the uncharacterized membrane proteins of H. pylori. In this study, a reliable benchmark dataset consisted of 114 membrane and 219 nonmembrane proteins was constructed based on UniProt. A support vector machine- (SVM-) based model was developed for discriminating H. pylori membrane proteins from nonmembrane proteins by using sequence information. Cross-validation showed that our method achieved good performance with an accuracy of 91.29%. It is anticipated that the proposed model will be useful for the annotation of H. pylori membrane proteins and the development of new anti-H. pylori agents.

To increase antibody secretion and dose sparing, squalene-in-water aluminium hydrogel (alum)-stabilised emulsions (ASEs) have been developed, which offer increased surface areas and cellular interactions for higher antigen loading and enhanced immune responses. Nevertheless, the squalene (oil) in previous attempts suffered from limited oxidation resistance, thus, safety and stability were compromised. From a clinical translational perspective, it is imperative to screen the optimal oils for enhanced emulsion adjuvants. Here, because of the varying oleic to linoleic acid ratio, soybean oil, peanut oil, and olive oil were utilised as oil phases in the preparation of aluminium hydrogel-stabilised squalene-in-water emulsions, which were then screened for their stability and immunogenicity. Additionally, the underlying mechanisms of oil phases and emulsion stability were unravelled, which showed that a higher oleic to linoleic acid ratio increased anti-oxidative capabilities but reduced the long-term storage stability owing to the relatively low zeta potential of the prepared droplets. As a result, compared with squalene-in-water ASEs, soybean-in-water ASEs exhibited comparable immune responses and enhanced stability. By optimising the oil phase of the emulsion adjuvants, this work may offer an alternative strategy for safe, stable, and effective emulsion adjuvants. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11705-021-2123-1 and is accessible for authorized users.

Seed deterioration during rice seed storage can lead to seed vigor loss, which adversely affects agricultural production, the long-term preservation of germplasm resources, and the conservation of species diversity. However, the mechanisms underlying seed vigor maintenance remain largely unknown. In this study, 16 hybrid rice combinations were created using four sterile lines and four restorer lines that have been widely planted in southern China. Following artificial aging and natural aging treatments, germination percentage and metabolomics analysis by gas chromatography–mass spectrometry was used to identify the metabolite markers that could accurately reflect the degree of aging of the hybrid rice seeds. Significant differences in the degree of seed deterioration were observed among the 16 hybrid rice combinations tested, with each hybrid combination having a different germination percentage after storage. The hybrid rice combination with the storage-resistant restorer line Guanghui122 exhibited the highest germination percentage under both natural and artificial storage. A total of 89 metabolic peaks and 56 metabolites were identified, most of which were related to primary metabolism. Interestingly, the content of galactose, gluconic acid, fructose and glycerol in the seeds increased significantly during the aging process. Absolute quantification indicated that galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds under the different aging treatments. The galactose content was significantly positively correlated with gluconic acid content. Additionally, glycerol showed a significant negative correlation with the germination percentage in most hybrid combinations. Based on the metabolomics analysis, metabolite markers that could accurately reflect the aging degree of hybrid rice seeds were identified. Galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds, which suggested that these metabolites could constitute potential metabolic markers of seed vigor and aging. These findings are of great significance for the rapid and accurate evaluation of seed aging degree, the determination of seed quality, and the development of molecular breeding approaches for high-vigor rice seeds. Supplementary Information The online version contains supplementary material available at 10.1186/s12284-022-00552-w.

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

Renal ischemia-reperfusion (I/R) injury may lead to acute kidney injury, which is characterized by high morbidity and mortality rates. Resveratrol (RSV) can be extracted from Chinese herbs, and multiple animal experiments have demonstrated its potential for renal protection. This systematic review evaluates the protective effect of RSV against renal I/R injury in animal models. The PubMed, Embase, Web of Science, and Science Direct databases were searched for animal experiments related to RSV in renal I/R injury from their establishment to June 2022. In total, 19 studies were included with 249 animals (129 treated with RSV and 120 as controls). The pooled analysis revealed that RSV administration significantly decreased serum creatinine (SCr) levels (16 studies, n = 243, WMD = −58.13, 95% CI = −79.26 to −37.00, p < 0.00001) and blood urea nitrogen (BUN) levels (12 studies, n = 163, WMD = −34.37, 95% CI = −46.70 to −22.03, p < 0.00001) in the renal I/R injury model. The level of malondialdehyde (MDA), an oxidative stress index, was alleviated [7 studies, n = 106, standardized mean difference (SMD) = −6.05, 95% CI = −8.90 to −3.21, p < 0.0001] and antioxidant enzymes such as glutathione (GSH) (7 studies, n = 115, SMD = 9.25, 95% CI = 5.51–13.00, p < 0.00001) and catalase (CAT) (4 studies, n = 59, SMD = 8.69, 95% CI = 4.35–13.03, p < 0.0001) were increased after treatment of RSV. The subgroup analysis suggested that 5–10 mg/kg of RSV optimally protects against renal I/R injury as both the BUN and SCr levels were significantly decreased at this dosage. The protective effects of RSV against renal I/R injury might be attributed to multiple mechanisms, such as inhibiting oxidative stress, apoptosis, inflammation, fibrillation, and promoting autophagy. For a deeper understanding of the protective effects of RSV, experimental studies on animal models and large randomized controlled trials in humans are needed.

In this article, the bond performance between recycled concrete and corroded steel bars is analyzed by the nonlinear numerical simulation. The result shows that the maximum bond strength between recycled concrete and steel bar decreases with the increase in steel bar corrosion rate; when the recycled concrete strength is large, the simulated maximum bond strength is in good agreement with the experimental maximum bond strength; when the recycled concrete strength is small, the simulated maximum bond strength is in relatively poor agreement with the experimental maximum bond strength, but there is still an error within the allowable range; the slip between recycled concrete and steel bar increases with the increase in steel bar corrosion rate; when the steel bar corrosion rate exceeded 5%, the bond strength decreases more rapidly; the maximum bond strength increases with the increase in specimen sizes under the same steel bar corrosion rate; the maximum bond strength decreases with the increase in steel bar diameter under the same steel bar corrosion rate.

The Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a threatened monotypic genus species endemic to Hengduan Mountains. In this study, we present a high-quality, chromosome-level reference genome for A. bracteata, constructed using long reads, short reads, and Hi-C technology. We characterized its genetic diversity, population structure, demographic history, and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single-copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged approximately 104.5 million years ago (mya). Whole-genome resequencing based on population genetic analysis revealed that the division of the 14 populations into ten distinct clusters reflected geographic divergence, and three high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicated that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units (CUs) for the conversation and management of threatened species. Our high-quality genome represents a valuable resource for revealing the underlying molecular mechanisms of adaptive evolution in the future and sheds insight into further comparative genomic analysis with other Velloziaceae species.

Controlling the process of CHO cell fed-batch culture is critical for biologics quality control. However, the biological complexity of cells has hampered the reliable process understanding for industrial manufacturing. In this study, a workflow was developed for the consistency monitoring and biochemical marker identification of the commercial-scale CHO cell culture process through H NMR assisted with multivariate data analysis (MVDA). Firstly, a total of 63 metabolites were identified in this study object in H NMR spectra of the CHO cell-free supernatants. Secondly, multivariate statistical process control (MSPC) charts were used to evaluate process consistency. According to MSPC charts, the batch-to-batch quality consistency was high, indicating the CHO cell culture process at the commercial scale was well-controlled. Then, the biochemical marker identification in the cell logarithmic expansion, stable growth, and decline phases were provided through orthogonal partial least square discriminant analysis (OPLS-DA) based S-line plots. L-glutamine, pyroglutamic acid, 4-hydroxyproline, choline, glucose, lactate, alanine, and proline were determined as biochemical markers of the logarithmic growth phase. Isoleucine, leucine, valine, acetate, and alanine were determined as biochemical markers of the stable growth phase. Acetate, glycine, glycerin, and gluconic acid were identified as biochemical markers of the cell decline phase. The workflow proposed in this study demonstrates that the combination of MVDA tools and H NMR technology is highly appealing to the research of the biomanufacturing process, and applies well to provide critical guidance in future work on consistency evaluation and biochemical marker monitoring of the production of other biologics.

In dimorphic fungi, the yeast-to-filament transition critical for cell survival under nutrient starvation is controlled by both activators and repressors. However, very few filamentation repressors are known. Here we report that, in the dimorphic yeast Yarrowia lipolytica, the conserved transcription factor YlNrg1 plays a minor role whereas Fts1, a newly identified Zn(II)

In the last few decades, hyperuricemia has drawn increasing attention owing to its global prevalence. Observational surveys have manifested that there is a relation between hyperuricemia and increased risks of hypertension, chronic kidney disease, cardiovascular events, metabolic disorders, end stage renal disease, and mortality. As alternatives, Traditional Chinese medicinal herbs have demonstrated concrete effects in mitigating hyperuricemia in different experiments. Researchers have made efforts to investigate the role of herbal medicine in attenuating hyperuricemia. This review focuses on traditional Chinese herbal medicines that have been reported to ameliorate hyperuricemia in experimental studies.

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host receptors with the exception of ACE2. Furthermore, ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV, suggesting the involvement of other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, and KREMEN1, were identified with diverse S-binding affinities and patterns. ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo. SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types, and the expression of ASK together displays a markedly stronger correlation with virus susceptibility than that of any individual receptor at both the cell and tissue levels. The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies. Our study revealed an interacting host receptome of SARS-CoV-2, and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry, providing insight into SARS-CoV-2 tropism and pathogenesis, as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.

The coronavirus disease 2019 (COVID-19) pandemic causes an overwhelming number of hospitalization and deaths with a significant socioeconomic impact. The vast majority of studies indicate that asthma and allergic diseases do not represent a risk factor for COVID-19 susceptibility nor cause a more severe course of disease. This raises the opportunity to investigate the underlying mechanisms of the interaction between an allergic background and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The majority of patients with asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies and drug allergies exhibit an over-expression of type 2 immune and inflammatory pathways with the contribution of epithelial cells, innate lymphoid cells, dendritic cells, T cells, eosinophils, mast cells, basophils, and the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31. The potential impact of type 2 inflammation-related allergic diseases on susceptibility to COVID-19 and severity of its course have been reported. In this review, the prevalence of asthma and other common allergic diseases in COVID-19 patients is addressed. Moreover, the impact of allergic and non-allergic asthma with different severity and control status, currently available asthma treatments such as inhaled and oral corticosteroids, short- and long-acting β2 agonists, leukotriene receptor antagonists and biologicals on the outcome of COVID-19 patients is reviewed. In addition, possible protective mechanisms of asthma and type 2 inflammation on COVID-19 infection, such as the expression of SARS-CoV-2 entry receptors, antiviral activity of eosinophils and cross-reactive T-cell epitopes, are discussed. Potential interactions of other allergic diseases with COVID-19 are postulated, including recommendations for their management.

The Hedgehog (Hh) signalling pathway plays a critical role in regulating liver lipid metabolism and related diseases. However, the underlying mechanisms are poorly understood. Here, we show that the Hh signalling pathway induces a previously undefined long non-coding RNA (Hilnc, Hedgehog signalling-induced long non-coding RNA), which controls hepatic lipid metabolism. Mutation of the Gli-binding sites in the Hilnc promoter region (HilncBM/BM) decreases the expression of Hilnc in vitro and in vivo. HilncBM/BM and Hilnc-knockout mice are resistant to diet-induced obesity and hepatic steatosis through attenuation of the peroxisome proliferator-activated receptor signalling pathway, as Hilnc directly interacts with IGF2BP2 to enhance Pparγ mRNA stability. Furthermore, we identify a potential functional human homologue of Hilnc, h-Hilnc, which has a similar function in regulating cellular lipid metabolism. These findings uncover a critical role of the Hh-Hilnc-IGF2BP2 signalling axis in lipid metabolism and suggest a potential therapeutic target for the treatment of diet-induced hepatic steatosis.

Ogataea minuta is a methylotrophic yeast that is closely related to Ogataea (Hansenula) polymorpha. Like other methylotrophic yeasts, O. minuta possesses strongly methanol-inducible genes, such as AOX1. We have focused on O. minuta as a host for the production of heterologous glycoproteins. However, it remained unknown how the AOX1 promoter is regulated in O. minuta. To elucidate regulation mechanisms of the AOX1 promoter, we adopted an assay system to quantitate AOX1 promoter activity using the PHO5 gene, which encodes an acid phosphatase, of Saccharomyces cerevisiae. The promoter activity assay revealed that glycerol, as well as glucose, cause strong catabolite repression of AOX1 expression in O. minuta. To investigate what factors are involved in transcription of the AOX1 promoter in O. minuta, we cloned three putative transcription factor genes, TRM1, TRM2, and MPP1, as homologues of other methylotrophic yeast species. Deletion mutants of these genes all showed decreased induction of the AOX1 promoter when methanol was added as the sole carbon source, indicating that these genes are indeed involved in AOX1 promoter regulation in O. minuta. Double deletion and constitutive expression of these transcription factor genes indicated that TRM1 and MPP1 regulate the transcription of AOX1 in the same pathway, while TRM2 regulates it in another pathway. By reverse transcription-qPCR, we also found that these two pathways compensate for each other and have crosstalk mechanisms with each other. A possible model for regulation of the AOX1 promoter in O. minuta was shown.

BACKGROUND Tyrophagus putresecentiae is an important mite species in rural and urban environments, causing sensitization and allergic disease. While evidence suggests that microRNAs (miRNAs) may regulate the expression of allergen-encoding genes, no study has directly investigated this possibility. Here, this gap was addressed by profiling miRNAs and elucidating their target allergen messenger RNAs (mRNAs) in this mite species. METHODS Small RNA and transcriptome libraries were constructed for eggs, larvae, nymphs, and adults. After deep miRNA and whole-transcriptome sequencing were performed, the miRNA and allergen-encoding mRNA regulatory networks were explored. RESULTS A total of 540 miRNAs were identified, including 155 with expression levels differing significantly across the four mite developmental stages (p

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Yan Qu,1 Xien Feng,2 Jin’ning Liang,2 Junru Liu,3 Dong Gao2 1Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, 264003, Shandong, People’s Republic of China; 3Department of Dermatology, Yantai Yuhuangding Hospital Laishan Branch, Yantai, 264003, Shandong, People’s Republic of ChinaCorrespondence: Dong Gao Email gaodong_yhd@163.comObjective: We aimed to investigate picosecond laser effects regarding rat tattoo removals. We systematically detected the metabolic pathways considering tattoo pigment particles in rat models.Materials and Methods: We employed fluorescein to mark the tattoo dye and utilized a pattern needle to prepare tattoo on rat so as to establish the tattoo removal effects of picosecond laser methods employing animal models. We applied a picosecond laser to process the tattoo and observed the effects along with metabolic pathways for tattoo removal via pathology and imaging approaches.Results: Based on the results of characterization, pathology and fluorescence, we discovered that the picosecond laser could effectively remove the pigment particles on rat skin, part of which would be metabolized out of the body through the circulatory system. After picosecond laser treatment, the fluorescence intensity of the rat skin engraved part was gradually weakened. At 8 h after the treatment, the metabolic organs had weak fluorescence, and there was no fluorescence in the metabolic organs at 12 h and 24 h after the treatment.Conclusion: The picosecond laser had perfect tattoo removal effects, which could be utilized as a reference for clinical tattoo removal.Keywords: tattoo, picosecond laser, pattern engraving, dye

Clear‐cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy. The pathogenesis of the disease is currently poorly understood, and the prognosis is poor. Therefore, in this study, we focused on exploring and identifying genes and signal transduction pathways that are closely related to ccRCC. Differentially expressed genes (DEGs) were analyzed using the renal cell oncogene expression profiles GSE100666 and GSE68417. DAVID evaluation of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was used. We constructed a protein–protein interaction (PPI) network of DEGS using Cytoscape software and analyzed the submodules with the CytoHubba plugin. Finally, we performed western blot, immunohistochemistry, and PCR validation by collecting tissues, and also utilized cells for in vitro functional analysis of ceruloplasmin (CP). In total, 202 DEGs (52 upregulated and 150 downregulated genes) were identified. Upregulated DEGs are significantly rich in angiogenesis, cell adhesion, and response to hypoxia, whereas downregulated DEGs are involved in intracellular pH regulation, excretion, coagulation, and chloride transmembrane transport. We selected the interactions of the top 20 hub genes provided by the PPI network, all of which are involved in important physiological pathways in vivo, such as complement and coagulation cascades. Tissue protein assays demonstrated that renal cancer highly expressed CP, while in vitro experiments showed that CP could promote the invasion of renal cancer cells. Our study suggests that ALB, C3, LOX, HRG, CXCR4, GPC3, SLC12A3, CP, and CASR may be involved in the development of ccRCC, and is expected to provide theoretical support for future studies on the diagnosis and targeted therapy of ccRCC., DEGs in clear cell renal cell carcinoma (ccRCC) were identified and their expression analyzed in ccRCC patient tissues and an RCC cell line. Tissue protein assays demonstrated that renal cancer highly expressed ceruloplasmin (CP), and in vitro experiments showed that CP could promote the invasion of renal cancer cells. Overall, CP may promote the poor prognosis of renal cancer.

In this paper, magnetometer-based orbit determination via the fast reconstruction of a 3-D decoupled geomagnetic field (TDGF) model is examined. For the TDGF model, the three components of the geom...

The yeast-to-filament transition is an important cellular response to environmental stimulations in dimorphic fungi. In addition to activators, there are repressors in the cells to prevent filament formation, which is important to keep the cells in the yeast form when filamentation is not necessary. However, very few repressors of filamentation are known so far. Here, we identify a novel repressor of filamentation in the dimorphic yeast Yarrowia lipolytica, Fts2, which is a C

Background Tumor metabolic reprogramming has attracted extensive attention, and mitochondria play a vital role in this process as a metabolic hub. Despite increasing evidence that mitochondria are involved in breast tumorigenesis, the impact of mitochondria-related genes on breast cancer remains unclear. In this study, we aimed to construct a novel mitochondria-related gene signature through bioinformatic strategies to predict and stratify the prognosis, immune infiltration, and treatment response of breast cancer patients. Methods The transcriptomic data and clinical features of breast cancer samples were extracted from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium databases. We constructed a mitochondria-related gene signature to predict survival, and Cox regression and receiver operating characteristic were used to evaluate the overall predictive performance. Subsequently, we combined the risk scores with corresponding clinical features to construct a nomogram model and evaluated the model’s accuracy by clinical calibration curve and decision curve analysis. After dividing patients based on risk scores, several immune-related analyses were performed to compare the immune infiltration status between different groups. Finally, we compared the mutation status and drug sensitivity to explore the treatment response and underlying mechanism of the difference in prognosis. Results We constructed an eight mitochondria-related gene risk signature by bioinformatic strategies and verified it by Cox regression, receiver operating characteristic, calibration curve and decision curve analyses. Patients with low-risk score have a better prognosis, enhanced immune infiltration, significantly different mutation landscapes, and a more sensitive response to antitumor drugs, which may account for the favorable survival. Conclusion The mitochondria-related gene signature is a novel prognostic risk signature that can be used as a predictor for patient stratification in breast cancer. In addition, this signature can effectively distinguish the immune infiltration and drug sensitivity status of patients. This may provide a new perspective for the treatment of breast cancer focusing on mitochondria.

Microbial induced calcium carbonate precipitation (MICP) is widely common in nature, which belongs to biomineralization, and has been explored carefully in recent decades. The research studied the main factors including temperature, initial pH value and Ca2+ concentration on bacterial growth and carbonic anhydrase activity by Bacillus mucilaginosus producing extracellular carbonic anhydrase, and revealed the biomineralization process of MICP by Ca2+ concentration and calcification rate in alkali environment. Meanwhile, microbial healing agent containing spores and calcium nitrate was prepared for the early age concrete cracks. The self-healing efficiency was assessed by crack closure rate, water permeability repair rate, healing depth and so on. Moreover, the precipitations generated at the crack mouth of specimens were analyzed by scanning electron microscope (SEM) equipped with an energy dispersive spectrometry (EDS), and X-ray diffraction (XRD). After 28 d healing time of dry-wet cycles, compared with reference, the crack closure rate with the crack width up to 0.339 mm could reach 95.62%, the water permeability repair rate was 87.54%. In addition, the precipitations generated were most at the crack surface, with the increase of the crack depth, the precipitations gradually decreased. XRD analysis showed that the precipitations at the crack mouth were calcite CaCO3. Meanwhile, the self-healing mechanism of mortar cracks was discussed in detail. What’s more, the CA produced by the bacteria could accelerate the hydration of CO2 in the air, and the mineralization reaction efficiency was also high. In particular, there is no other pollution in the whole mineralization process, and the self-healing system is environmentally friendly, which provides a novel idea and method for the application of microbial self-healing concrete.

In clinical practice, injectable drug combination (IDC) usually provides good therapeutic effects for patients. Numerous clinical studies have directly indicated that inappropriate IDC generates adverse drug events (ADEs). The clinical application of injections is increasing, and many injections lack relevant combination information. It is still a significant need for experienced clinical pharmacists to participate in evidence-based drug decision making, monitor medication safety, and manage drug interactions. Meanwhile, a large number of injection pairs and dosage combinations limit exhaustive screening. Here, we present a prediction framework, called DeepIDC, that can expediently screen the feasibility of IDCs using heterogeneous information with deep learning. This is the first specific prediction framework to identify IDCs.Since the interaction between the injected drugs may occur in the direct physical and chemical reactions at the time of mixing or may be the indirect interaction of their drug targets and pathways, we used molecular fingerprints, drug-target associations, and drug-pathway associations to convert injections into a string of digital vectors. Then, based on these injection vectors, we combined a bidirectional long short-term memory and a feed-forward neural network to build a prediction model for accurate and instructive prediction of IDC.In three realistic evaluation scenarios, DeepIDC has achieved ideal prediction results. Furthermore, compared with the other five machine-learning methods, the proposed predictor is more efficient and robust. Among the top 30 potential IDCs of each IDC class predicted by DeepIDC, we found that 9 cases were experimentally verified in the literature or available on Drug.com.The information we extracted in vivo and in vitro can effectively characterize injectable drugs. DeepIDC developed based on deep learning algorithm provides a valuable unified framework for new IDC discovery, which can make up for the lack of IDC information and predict potential IDC events.

Objectives To investigate the clinical effect of percutaneous vertebroplasty (percutaneous vertebroplasty, PVP) and percutaneous kyphoplasty (percutaneous kyphoplasty, PKP), PVP) in the treatment of osteoporotic vertebral fracture (osteoporotic vertebral compression fractures, OVCF). Methods From March 2016 to June 2019, we treated the patients who were admitted to our hospital from March 2016 to June 2019. The clinical data of 150 OVCF patients were analyzed retrospectively, and it was divided into PKP group (group A), PVP group (group B) and PVP + traditional Chinese medicine hyperextraction reduction method group (group C) according to different operation methods, and 50 cases in each group. Preoperative, postoperative 1d,3-month,6-month,1-year pain-visual analogue scale (VAS) was used to assess the degree of pain relief of the back and back of the patient, and the range of motion of the thoracolumbar spine was assessed. The recovery of degree, the recovery of kyphosis Cobb angle, the refracture of injured vertebrae and adjacent vertebrae after operation, and the trend of long-term stability of spine were followed up. Results The operation was smooth and there were no complications such as incision infection and deep venous thrombosis. At 3 months and 6 months after operation, there was significant difference between PVP overextended reduction group (group C) and PKP group (group A), PVP group (group B). The recovery rate of Cobb angle in sagittal plane of injured vertebrae was compared before and after operation. 1 day, 3 months, 6 months, 1 year follow-up. There was no significant difference between group C and group A and group B (P 0.05). There was no significant difference in the improvement rate of ODI between group C and group A. there was no significant difference in the improvement rate of ODI between group C and group A. there was no significant difference in the improvement rate of ODI between group C and group A at 1 day, 3 months and 1 year after operation. During the follow-up of 6 months after operation, there was significant difference between group C and group A and group B (P 0.05). There was a significant difference between group C and group A and B at 1 month, 3 months and 6 months after operation (P 0.05). Conclusions The three methods of reduction and fixation (PKP,PVP and PVP) are effective in relieving pain, strengthening vertebral body, stabilizing injured vertebra, restoring vertebral body height and correcting kyphosis of thoracolumbar spine. However, in the course of long-term follow-up, simple PVP The residual low back pain or recurrence in patients with PKP, the loss of the height of injured vertebrae, the occurrence of fractures and even the complications of refracture of adjacent vertebrae after enhanced operation, resulting in the decrease of the balance and long-term stability of spinal muscle and bone system. And then increase the degeneration process of the thoracolumbar segment of the spine.

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

We observed behavior response of overwintering2018年11—12月在河南民权国家湿地公园,采用定点观察法、扫描取样法对越冬青头潜鸭在不同天气条件下的行为响应模式进行研究。结果表明: 在晴天,静息、飞行、运动是青头潜鸭越冬期的优势行为(65.5%),觅食、修整是次要行为(31.9%);行为节律表现为上午觅食、中午静息、下午觅食修整;飞行通常发生在觅食高峰前,运动行为多与其他行为相伴,其时间分配与觅食呈正响应,与静息呈负响应。相较于晴天,阴雨天青头潜鸭增加了对静息和觅食的时间分配,静息、觅食和运动为阴雨天的主要行为(76.5%),修整、飞行为次要行为(20.3%);觅食和静息的高峰时段后移,傍晚时达到高峰,飞行和修整时间显著减少。与晴天相比,雾霭天青头潜鸭静息、觅食、运动和修整的时间分配增加,飞行行为减少;觅食高峰后移至中午和下午,静息高峰后移至下午;静息、运动和觅食为雾霭天的优势行为(70.6%),修整和飞行为次要行为(27.5%)。研究表明,不同天气条件下,民权湿地公园青头潜鸭的越冬期行为在时间分配、行为节律、优势行为方面存在一定的响应;阴雨天和雾霭天青头潜鸭会分配更多的静息和觅食时间,并通过增加能量摄入和减少耗能行为应对恶劣天气。.

Deuterium water (D

The electrolytic aluminum operation accidents have caused great losses to the country and people. Therefore, taking two typical accidents of explosion and leakage in electrolytic aluminum production as the research object, the form of accident risk characterization was explored and a risk characterization visualization system was designed. Based on the methods of risk assessment and characterization, the likelihood and the consequence of the accident were studied. The influencing factors of likelihood and a kind of Euclidean distance formula were used to characterize the likelihood. The consequence portion was characterized by two components, with one being the failure degree determined by the accident and the other being the exposure degree of people and equipment. The intensity of event was used to characterize the failure degree and the spatial search model was used to characterize the exposure degree. Finally, the visual system of electrolytic aluminum operation accidents was established that based on the risk characterization model.

In recent decades, extreme climate occurred frequently on the Loess Plateau. It is thus particularly important to study and predict the occurrence of extreme climate. Available researches on extreme climate mainly focus on the changing characteristics of the event itself, but ignore the correlation between average temperature and its changing trend. We used linear trend estimation, Mann-Kendall test, sliding近几十年来,黄土高原极端气候频发,研究和预测极端气候的发生显得尤为重要。目前,关于极端气候的研究多关注事件本身的变化特征,而忽略了平均气温与其变化趋势的相关分析。本研究基于1986—2019年黄土高原79个气象站的逐日最高气温、最低气温和平均气温资料,采用线性倾向估计、Mann-Kendall检验、滑动

Precise timing of granitoids and constraints of their magma sources are critical to understanding the subduction–collision tectonic evolution of the Altun orogenic belt (AOB), a vital part of the Q...

Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. This strategy provides a facile method for developing biomimetic hydrogels with high antibacterial capability.