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Abstract The coordination between kinases and phosphatases is crucial for regulating the phosphorylation levels of essential signaling molecules. Methods enabling precise control of kinase activities are valuable for understanding the kinase functions and for developing targeted therapies. Here, we use the abscisic acid (ABA)-induced proximity system to reversibly control kinase signaling by recruiting phosphatases. Using this method, we found that the oncogenic tyrosine kinase BCR::ABL1 can be inhibited by recruiting various cytoplasmic phosphatases. We also discovered that the oncogenic serine/threonine kinase BRAF(V600E), which has been reported to bypass phosphorylation regulation, can be positively regulated by protein phosphatase 1 (PP1) and negatively regulated by PP5. Additionally, we observed that the dual-specificity kinase MEK1 can be inhibited by recruiting PP5. This suggests that bifunctional molecules capable of recruiting PP5 to MEK or RAF kinases could be promising anticancer drug candidates. Thus, the ABA-induced dephosphorylation method enables rapid screening of phosphatases to precisely control kinase signaling.

Abstract Diatoms often outnumber other eukaryotic algae in the oceans, especially in coastal environments characterized by frequent fluctuations in light intensity. The identities and operational mechanisms of regulatory factors governing diatom acclimation to high light stress remain largely elusive. Here, we identified the AUREO1c protein from the coastal diatom Phaeodactylum tricornutum as a crucial regulator of non-photochemical quenching (NPQ), a photoprotective mechanism that dissipates excess energy as heat. AUREO1c detects light stress using a light-oxygen-voltage (LOV) domain and directly activates the expression of target genes, including LI818 genes that encode NPQ effector proteins, via its bZIP DNA-binding domain. In comparison to a kinase-mediated pathway reported in the freshwater green alga Chlamydomonas reinhardtii, the AUREO1c pathway exhibits a faster response and enables accumulation of LI818 transcript and protein levels to comparable degrees between continuous high-light and fluctuating-light treatments. We propose that the AUREO1c-LI818 pathway contributes to the resilience of diatoms under dynamic light conditions.

Hepatocellular Carcinoma (HCC) is a serious primary solid tumor that is prevalent worldwide. Due to its high mortality rate, it is crucial to explore both early diagnosis and advanced treatment for HCC. In recent years, multi-omics approaches have emerged as promising tools to identify biomarkers and investigate molecular mechanisms of biological processes and diseases. In this study, we performed proteomics, phosphoproteomics, metabolomics, and lipidomics to reveal the molecular features of early- and advanced-stage HCC. The data obtained from these omics were analyzed separately and then integrated to provide a comprehensive understanding of the disease. The multi-omics results unveiled intricate biological pathways and interaction networks underlying the initiation and progression of HCC. Moreover, we proposed specific potential biomarker panels for both early- and advanced-stage HCC by overlapping our data with CPTAC database for HCC diagnosis, and deduced novel insights and mechanisms related to HCC origination and development, such as glucose depletion during tumor progression, ROCK1 deactivation and GSK3A activation.

Carnation (Dianthus caryophyllus L.) is a typical ethylene-sensitive cut flower. Variations in carnation vase life and sensitivity to ethylene have been reported, but no detailed analysis has been performed to date. In order to investigate the ethylene sensitivity of different cut carnation varieties and study the effect of ethylene on postharvest physiological changes of different carnation varieties, 14 varieties were used to explore ethylene sensitivity, and six varieties were used to analyze the release pattern of endogenous ethylene and the expression pattern of related genes. The results showed that among the 14 carnation varieties, 'Master' had the strongest ethylene sensitivity and 'Snow White' had the weakest ethylene sensitivity. Ethylene release changes of 'Master' are the terminal ascending type, and 'Cloud Shium', 'Little Pink', 'Seashell', 'Freedom' and 'Snow White' are the similar ethylene leap type. Ethylene biosynthesis genes DcACS1 and DcACO1 of 'Master' were up-regulated the most, and DcACO1 of 'Snow White' was the least up-regulated. The transient silencing and overexpression of DcACS1 and DcACO1 were performed and it was found that transient silencing can significantly delay aging, and overexpression significantly accelerates aging. This study laid the foundation for further research on the molecular mechanism of ethylene regulation of postharvest senescence of cut flowers of carnation, and also indicated the direction for further breeding and artificial screening of new storage tolerant carnation species by gene editing technology.

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14−CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature (“cluster 6”) that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

Finite Gaussian mixture models are powerful tools for modeling distributions of random phenomena and are widely used for clustering tasks. However, their interpretability and efficiency are often degraded by the impact of redundancy and noise, especially on high-dimensional datasets. In this work, we propose a generative graphical model for parsimonious modeling of the Gaussian mixtures and robust unsupervised learning. The model assumes that the data are generated independently and identically from a finite mixture of robust factor analyzers, where the features’ salience is adjusted by an active set of latent factors to allow a violation of the local independence assumption. For the model inference, we propose a structured variational Bayes inference framework to realize simultaneous clustering, model selection and outlier processing. Performance of the proposed algorithm is evaluated by conducting experiments on artificial and real-world datasets. Moreover, an application on the high-dimensional machine learning task of handwritten alphabet recognition is introduced.

Context Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings.Objective This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment.Materials and methods C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro.Results Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood–brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were −7.0 to −5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice.Discussion Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline.Conclusion Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.

Abstract Introduction Recent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released from Talaromyces marneffei (T. marneffei)‐infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. Methods Exosomes derived from macrophages infected with T. marneffei were extracted and characterized by transmission electron microscopy and western blot. Moreover, we examined exosomes that modulated IL‐10 and TNF‐α secretion and activation of p42 and p44 extracellular signal‐regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. Results We found that exosomes promoted activation of ERK1/2 and autophagy, IL‐10 and TNF‐α secretion in human macrophages. Further, exosomes decreased the multiplication of T. marneffei in T. marneffei‐infected human macrophages. Interestingly, exosomes isolated from T. marneffei‐infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages. Conclusion Our studies are the first to demonstrate that exosomes isolated from T. marneffei‐infected macrophages can modulate the immune system to control inflammation, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine production during T. marneffei infection.

Summary: T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here, we show that in an inflammation model mimicking bacterial infection using lipopolysaccharide, the expression of many Tas2rs was significantly upregulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly celltype specific and lipopolysaccharide increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-lasting effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

Abstract Background Plant AT-rich sequence and zinc-binding (PLATZ) proteins belong to a novel class of plant-specific zinc-finger-dependent DNA-binding proteins that play essential roles in plant growth and development. Although the PLATZ gene family has been identified in several species, systematic identification and characterization of this gene family has not yet been carried out for Tartary buckwheat, which is an important medicinal and edible crop with high nutritional value. The recent completion of Tartary buckwheat genome sequencing has laid the foundation for this study. Results A total of 14 FtPLATZ proteins were identified in Tartary buckwheat and were classified into four phylogenetic groups. The gene structure and motif composition were similar within the same group, and evident distinctions among different groups were detected. Gene duplication, particularly segmental duplication, was the main driving force in the evolution of FtPLATZs. Synteny analysis revealed that Tartary buckwheat shares more orthologous PLATZ genes with dicotyledons, particularly soybean. In addition, the expression of FtPLATZs in different tissues and developmental stages of grains showed evident specificity and preference. FtPLATZ3 may be involved in the regulation of grain size, and FtPLATZ4 and FtPLATZ11 may participate in root development. Abundant and variable hormone-responsive cis-acting elements were distributed in the promoter regions of FtPLATZs, and almost all FtPLATZs were significantly regulated after exogenous hormone treatments, particularly methyl jasmonate treatment. Moreover, FtPLATZ6 was significantly upregulated under all exogenous hormone treatments, which may indicate that this gene plays a critical role in the hormone response of Tartary buckwheat. Conclusions This study lays a foundation for further exploration of the function of FtPLATZ proteins and their roles in the growth and development of Tartary buckwheat and contributes to the genetic improvement of Tartary buckwheat.

Summary: Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility and waning immunity maintain the pandemic, driving emergence of variants. We developed an inactivated SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with the Spike mutation D614G, produced in Vero cells in a scalable bioreactor, inactivated with β-propiolactone, purified by membrane-based steric exclusion chromatography, and adjuvanted with MF59-like adjuvant AddaVax. I-SARS-CoV-2 and a derived split vaccine induced persisting neutralizing antibodies in mice; moreover, lyophilized antigen was immunogenic. Following homologous challenge, I-SARS-CoV-2 immunized hamsters were protected against disease and lung pathology. In contrast with reports for widely used vaccines, hamster plasma similarly neutralized the homologous and the Delta (B.1.617.2) variant viruses, whereas the Omicron (B.1.1.529) variant was neutralized less efficiently. Applied bioprocessing approaches offer advantages regarding scalability and production, potentially benefitting worldwide vaccine coverage.

The site for the high Quxue Dam has a narrow canyon with very steep abutments and complex geology in Sichuan Province, China. Various types of embankment and concrete dams were considered and an asphalt-core embankment dam (ACED), 174 m high, was selected. The asphalt core is a slender impervious element in an embankment dam and some concerns have been raised about the reliability and safety of the asphalt-core type of dams (ACEDs). This paper presents the case study of the highest asphalt core dam ever built and presents measured and numerical analyses of the core deformations. A 3D non-linear FE analysis has been performed for the Quxue Dam, and the results have been compared with those computed by a 2D analysis to study the effects of the narrow canyon. The computed results are compared with the monitoring data from dam construction and first impoundment. The maximum settlement measured inside the embankment during construction was only about 0.7 m due to the good basaltic rockfill used and the heavy compaction in layers of only 1.0 – 1.2 m thickness. The results of the 3D analysis agree well with the measured downstream displacements and the deflected shape of the thin asphalt core during impoundment, while the 2D analysis overpredicted the maximum displacement by a factor of about two. At a reservoir level 3 m below full supply level, the maximum measured downstream core displacement was only about 80 mm due to the stiff rockfill and the restraining effects of the abutments in the narrow valley.The rockfill behaviour was modelled by the constitutive relationship proposed by Duncan and Chang (1970). The rockfill parameters were determined by laboratory tests prior to construction and were adjusted to better match field observations of vertical settlements during construction. As asphalt concrete exhibits pronounced visco-elastoplastic behaviour, the material modelling was based on long-term triaxial creep tests on samples drilled out of the dam core. The performance monitoring and numerical analysis results for the record-high Quxue ACED document that the concerns expressed about the asphalt core safety and behaviour is not warranted. The asphalt core type of dam is suitable even for high ACEDs in narrow valleys with steep abutments.

Summary: Identification of protein interactors is fundamental to understanding their functions. Here, we describe a modified protocol for tandem affinity purification coupled with mass spectrometry (TAP/MS), which includes two-step purification. We detail the S-, 2×FLAG-, and Streptavidin-Binding Peptide (SBP)- tandem tags (SFB-tag) system for protein purification. This protocol can be used to identify protein interactors and establish a high-confidence protein–protein interaction network based on computational models. This is particularly useful for identifying bona fide interacting proteins for subsequent functional studies.For complete details on the use and execution of this protocol, please refer to Bian et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In Gram-negative bacteria, lipoproteins are transported from the inner membrane (IM) to the outer membrane (OM) by the ATP-binding cassette (ABC) transporter LolCDE. Here the authors present cryo-EM structures of nanodisc-embedded LolCDE in different states, providing mechanistic insight into the transport mechanism.

Abstract Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7–12 µg/mL), followed by artemether (53–98 µg/mL), A. annua extracts (83–260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.

The transmembrane protein Wntless (WLS) is essential for the secretion of Wnt proteins, which are signaling molecules of the Wnt signaling pathways. Here, the authors present the 2.2 Å cryo-EM structure of human WLS in complex with Wnt3a and discuss mechanistic implications for the palmitoleoylation of Wnt3a that is required for WLS mediated Wnt secretion.

Abstract Background Walnut anthracnose induced by Colletotrichum gloeosporioides is a disastrous disease affecting walnut production. The resistance of walnut fruit to C. gloeosporioides is a highly complicated and genetically programmed process. However, the underlying mechanisms have not yet been elucidated. Results To understand the molecular mechanism underlying the defense of walnut to C. gloeosporioides, we used RNA sequencing and label-free quantitation technologies to generate transcriptomic and proteomic profiles of tissues at various lifestyle transitions of C. gloeosporioides, including 0 hpi, pathological tissues at 24 hpi, 48 hpi, and 72 hpi, and distal uninoculated tissues at 120 hpi, in anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts, which were defined through scanning electron microscopy. A total of 21,798 differentially expressed genes (DEGs) and 1929 differentially expressed proteins (DEPs) were identified in F26 vs. F423 at five time points, and the numbers of DEGs and DEPs were significantly higher in the early infection stage. Using pairwise comparisons and weighted gene co-expression network analysis of the transcriptome, we identified two modules significantly related to disease resistance and nine hub genes in the transcription expression gene networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs and DEPs revealed that many genes were mainly related to immune response, plant hormone signal transduction, and secondary metabolites, and many DEPs were involved in carbon metabolism and photosynthesis. Correlation analysis between the transcriptome data and proteome data also showed that the consistency of the differential expression of the mRNA and corresponding proteins was relatively higher in the early stage of infection. Conclusions Collectively, these results help elucidate the molecular response of walnut fruit to C. gloeosporioides and provide a basis for the genetic improvement of walnut disease resistance.

Abstract Background Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood. Results The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4–23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data. Conclusions The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

Penile squamous cell carcinoma (PSCC) is a cancer that is associated with significant mortality. Here, the authors develop a mouse model of PSCC by co-deletion of Smad4 and Apc in the androgen-responsive penile epithelium, and show synergistic efficacy of checkpoint therapy with cabozantinib or celecoxib in their model.

Hydraulic asphalt concrete is virtually impervious. Hydraulic fracturing due to the generation of pore water pressure can be generally excluded for asphalt facings and asphalt cores in embankment dams. However, when some cracks and/or large voids exist in the asphalt core in dams, hydraulic fracturing could take place during reservoir impounding. Cracks and/or large voids may be caused by either earthquake shaking, large differential settlements during construction and operation, or poor construction quality. Therefore, asphalt specimens with either cracks of different depths or large air porosity were prepared, and a model test apparatus was developed to investigate the possibility of hydraulic fracturing. Model tests were conducted on cylindrical asphalt concrete specimens of 100 mm in diameter and 180 mm in height. The top boundary of the specimens was either prevented (restrained) from moving in the vertical direction or free to move (unrestrained). The model test results for asphalt concrete with cracks under unrestraint conditions were numerically back-analysed. The model test results indicated that the cracks in the asphalt concrete under the restraint conditions could experience an “open–close” progress with increasing water pressure. That suggested that if the asphalt concrete were long, low water pressure would trigger a fracturing through the cracks. Under the unrestraint conditions, low water pressure could cause the asphalt specimens with either cracks or large air porosity to fail. The extensional strains at failure were reduced, and the reductions depended on the magnitude of the crack depth or air porosity. Suggestions are given for designing the asphalt core dams to reduce the possibility of the occurrence of cracks and/or dilations in the core, especially for dams in unfavourable geological and topographical conditions. A specialty contractor is preferable to do the asphalt core job to rule out the possibility of a weak bond between the layers and an air porosity larger than 3.0% in the core.

Atriplex canescens is a representative halophyte with excellent tolerance to salt. Previous studies have revealed certain physiological mechanisms and detected functional genes associated with salt tolerance. However, knowledge on the ROS scavenging system and regulatory mechanisms in this species when adapting to salinity is limited. Therefore, this study further analyzed the transcriptional changes in genes related to the ROS scavenging system and important regulatory mechanisms in A. canescens under saline conditions using our previous RNA sequencing data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation revealed that the differentially expressed genes (DEGs) were highly enriched in signal transduction- and reactive oxygen species-related biological processes, including “response to oxidative stress”, “oxidoreductase activity”, “protein kinase activity”, “transcription factor activity”, and “plant hormone signal transduction”. Further analyses suggested that the transcription abundance of many genes involved in SOD, the AsA-GSH cycle, the GPX pathway, PrxR/Trx, and the flavonoid biosynthesis pathway were obviously enhanced. These pathways are favorable for scavenging excessive ROS induced by salt and maintaining the integrity of the cell membrane. Meanwhile, many vital transcription factor genes (WRKY, MYB, ZF, HSF, DREB, and NAC) exhibited increased transcripts, which is conducive to dealing with saline conditions by regulating downstream salt-responsive genes. Furthermore, a larger number of genes encoding protein kinases (RLK, CDPK, MAPK, and CTR1) were significantly induced by saline conditions, which is beneficial to the reception/transduction of salt-related signals. This study describes the abundant genetic resources for enhancing the salt tolerance in salt-sensitive plants, especially in forages and crops.

BackgroundSelf-tracking technologies are widely used in people’s daily lives and health care. Academic research on self-tracking and the quantified self has also accumulated rapidly in recent years. Surprisingly, there is a paucity of research that reviews, classifies, and synthesizes the state of the art with respect to self-tracking and the quantified self. ObjectiveOur objective was to identify the state of the art of self-tracking and the quantified self in terms of health and well-being. MethodsWe have undertaken a systematic literature review on self-tracking and the quantified self in promoting health and well-being. After a rigorous literature search, followed by inclusions, exclusions, and the application of article quality assessment protocols, 67 empirical studies qualified for the review. ResultsOur results demonstrate that prior research has focused on 3 stakeholders with respect to self-tracking and the quantified self, namely end users, patients and people with illnesses, and health care professionals and caregivers. We used these stakeholder groups to cluster the research themes of the reviewed studies. We identified 11 research themes. There are 6 themes under the end-user cluster: user motivation and goal setting, usage and effects of self-tracking, continuance intention and long-term usage, management of personal data, rejection and discontinuance, and user characteristics. The patient and people with illnesses cluster contains three themes: usage experience of patients and people with illnesses, management of patient-generated data, and advantages and disadvantages in the clinical context. The health care professional and caregiver cluster contains two themes: collaboration among patients, health care professionals, and caregivers, and changes in the roles of patients and professionals. Moreover, we classified the future research suggestions given in the literature into 5 directions in terms of research designs and research topics. Finally, based on our reflections on the observations from the review, we suggest four future research directions: (1) users’ cognitions and emotions related to processing and interpreting the information produced by tracking devices and apps; (2) the dark side of self-tracking (eg, its adverse psychosocial consequences); (3) self-tracking as a societal phenomenon; and (4) systemic impacts of self-tracking on health care and the actors involved. ConclusionsThis systematic literature review contributes to research and practice by assisting future research activities and providing practitioners with a concise overview of the state of the art of self-tracking and the quantified self.

Background: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19. Methods: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres. Findings: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined. Interpretation: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection. Funding: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.

Thermal electron transfer across hydrogen bond remains largely unexplored. Here the authors demonstrate that electron self-exchange through hydrogen bonds is highly efficient and can proceed either via the known proton-coupled pathway or an overlooked proton-uncoupled pathway

The rapid development of wearable biosensors based on the Internet of Things provides a new solution for heart disease analysis and prediction of sudden death from heart failure. However, how to deal with a large amount of data generated by heart sound signals is an urgent problem to be solved. Based on the characteristics of heart sound signals, we propose a parallel compressive sensing model for the multi-channel synchronous acquisition of heart sound signals. Furthermore, we provide a series of experiments to assess the performance of the model. The experimental results demonstrate that the reconstruction speed of the proposed model is 9-10 times faster than that of the block sparse Bayesian learning algorithm and the orthogonal matching pursuit algorithm, and the reconstruction effect is better. Meanwhile, the proposed model can effectively reconstruct the normal heart sound signal and abnormal heart sound signal of four-channel synchronous acquisition. Therefore, the proposed model is feasibility.

Traditional construction practices showed that asphalt core construction rate was commonly 2 layers/day (0.4 m/day) before the year 2000. More than 2 layers/day has been concerned as it would be difficult to compact the third layer to reach the required density (void content of maximum 3%) as the sublayers are soft. However, the Zhaobishan embankment dam was located at a very special dam site and high construction rate was required. Based on reviewing successfully high construction rates of asphalt core test section with 0.8 m/day (4 layers/day) and 0.9 m/day (3 layers/day) extensive laboratory tests and 4 trial test sections near the Zhaobishan dam site were carried out to gain asphalt mix parameters and construction techniques before constructing the asphalt core. The 63.6 m high asphalt core for the 71 m high dam was completed in 159 days with intensively quality control during construction. The maximum construction rate was 0.92 m/day (4 layers/day). The dam with asphalt core has performed well since the completion year 2005. The dam case study has documented that asphalt core dam can be constructed in a high rate without compromising core quality. Based on practical experience, field observations, and investigations in recent years, one can now build asphalt core dams faster and more economically than before. The fact that one can significantly reduce the probability of overtopping during construction by increasing the construction rate, may be an important point in many situations.

Asphalt concrete is widely used in road and airport pavements and more recently also in the construction of impervious facings and central cores in dams and dykes. Asphalt concrete may be subjected to strongly acidic water when used in connection with storage of mine tailings (tailings dams). Acidic water reacts with bitumen and mineral materials and may cause deterioration of the behavior of asphalt concrete with time. The present study investigated effects of acidic water with time on aggregate-bitumen adhesion, bitumen penetration value, softening point and ductility, mass change of asphalt materials, and change in tensile strength for porous and impervious asphalt concrete. The test results show that impervious, hydraulic asphalt concrete is very resistant to acidic water and show insignificant deterioration of properties during the 3-year testing period used in the experiments.

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Poly aluminum-ferric Chloride (PAFC) is a new type of high efficiency coagulant. In this study, high iron type gangue is used as a main raw material. It is calcined at 675 °C for 1 h and 3% CaF2 is added to the calcined powder and reacted with 20% hydrochloric acid at 93 °C for 4 h. The leaching ratio of aluminum ions is 90% and that of iron ions is 91%. After Fe2+ ions are oxidized in the filtrate, CaCO3 is used to adjust the pH of the filtrate to 0.7. The microwave power is adjusted to 80 W and the filtrate is radiated for 5 min. After being aged for 24 h, PAFC product is obtained. The prepared PAFC is used to treat mine water and compared with the results of PAC and PAF, the turbidity removal ratio of PAFC is 99.6%, which is greater than 96.4% of PAC and 93.7% of PAF. PAFC is a mixture with different degrees of polymerization. It demonstrates that extracting aluminum and iron ions from high iron content gangue to prepare PAFC by microwave is efficient and feasible.

The low separation efficiency of photoinduced carriers in BiPO4 system limited its photocatalytic application. Here, lotus flower-like heterostructure Ti3C2/BiPO4 was constructed via a simple hydrothermal synthesis without surface active agent. The Schottky barrier between BiPiO4 and Ti3C2 interface could be formed due to the large gap in work function for two components, which efficiently promoted the photoproduced holes extraction, the separation of photogenerated electron-hole pairs and further inhibited photo-corrosion for BiPO4 and strengthened photostability. The heterostructure could totally photodegrade RhB under visible light irradiation for 20 min. The enhanced photocatalytic mechanism was explained in detail in this work. It is hoped that this photocatalytic system will be applied into another wastewater treatment and the used preparation method will be widely applied into many composite materials.

Extracting valuable elements from coal gangue is an important method for the utilization of coal gangue. In order to obtain the suitable technological conditions and the acid leaching kinetic model of leaching aluminum and iron ions from high-iron and low-aluminum coal gangue, the effects of calcination temperature, calcination time, and acid types on the leaching results of aluminum and iron ions are studied. The results show that when the gangue is calcined at 675 °C for 1 h, then the calcined gangue powder is leached by 6 mol/L hydrochloric acid at 93 °C for 4 h, the leaching ratio of iron ions is more than 90%, and that of aluminum ions is more than 60%. Furthermore, the acid leaching kinetic equations at 30 °C, 50 °C, 70 °C, and 90 °C are studied by three kinetic models, and the apparent activation energies of the reactions are calculated by the Arrhenius formula. The results show that the leaching behavior of aluminum and iron ions conformed to the “mixing control” model equation: “(1 − x)−1/3 − 1 + 1/3ln(1 − x) = kt + b”. The apparent activation energies of aluminum and iron ions are 55.5 kJ/mol and 55.8 kJ/mol, respectively. All these indicate that the acid leaching process is controlled by the “mixing control”.

The inactivation of von Hippel–Lindau (VHL) is critical for clear cell renal cell carcinoma (ccRCC) and VHL syndrome. VHL loss leads to the stabilization of hypoxia-inducible factor α (HIFα) and other substrate proteins, which, together, drive various tumor-promoting pathways. There is inadequate molecular characterization of VHL restoration in VHL-defective ccRCC cells. The identities of HIF-independent VHL substrates remain elusive. We reinstalled VHL expression in 786-O and performed transcriptome, proteome and ubiquitome profiling to assess the molecular impact. The transcriptome and proteome analysis revealed that VHL restoration caused the downregulation of hypoxia signaling, glycolysis, E2F targets, and mTORC1 signaling, and the upregulation of fatty acid metabolism. Proteome and ubiquitome co-analysis, together with the ccRCC CPTAC data, enlisted 57 proteins that were ubiquitinated and downregulated by VHL restoration and upregulated in human ccRCC. Among them, we confirmed the reduction of TGFBI (ubiquitinated at K676) and NFKB2 (ubiquitinated at K72 and K741) by VHL re-expression in 786-O. Immunoprecipitation assay showed the physical interaction between VHL and NFKB2. K72 of NFKB2 affected NFKB2 stability in a VHL-dependent manner. Taken together, our study generates a comprehensive molecular catalog of a VHL-restored 786-O model and provides a list of putative VHL-dependent ubiquitination substrates, including TGFBI and NFKB2, for future investigation.

DNA binding with one finger (Dof) proteins have been proven to be involved in multiple biological processes. However, genome-wide identification of the Dof gene family has not been reported for Tartary buckwheat (Fagopyrum tataricum). In this study, 35 FtDof proteins were identified, and they could be divided into nine phylogenetic subgroups. Proteins within the same subgroup had similar gene structure and motif composition. Moreover, abundant cis-acting elements were present in the promoter regions of FtDof genes. Segmental duplication was the primary driving force for the evolution of the FtDof gene family. Synteny analysis indicated that Tartary buckwheat was closer to dicotyledons, and more orthologous Dof genes existed among them. The expression pattern of FtDofs in different tissues and at different fruit developmental stages varied. Different tissues contained several genes that were specifically expressed. FtDof expression was mainly upregulated under methyl jasmonate treatment and downregulated under other hormone treatments. Taken together, FtDofs may play important roles in the growth and development of Tartary buckwheat and in response to abiotic and biotic stresses. Therefore, the genome-wide identification and expression pattern analysis of the Tartary buckwheat Dof gene family lays a foundation for further exploration of the functional characteristics of FtDofs in the future.

The COVID-19 pandemic continues to threaten healthcare systems worldwide due to the limited access to vaccines, suboptimal treatment options, and the continuous emergence of new and more transmissible SARS-CoV-2 variants. Reverse-genetics studies of viral genes and mutations have proven highly valuable in advancing basic virus research, leading to the development of therapeutics. We developed a functional and highly versatile full-length SARS-CoV-2 infectious system by cloning the sequence of a COVID-19 associated virus isolate (DK-AHH1) into a bacterial artificial chromosome (BAC). Viruses recovered after RNA-transfection of in vitro transcripts into Vero E6 cells showed growth kinetics and remdesivir susceptibility similar to the DK-AHH1 virus isolate. Insertion of reporter genes, green fluorescent protein, and nanoluciferase into the ORF7 genomic region led to high levels of reporter activity, which facilitated high throughput treatment experiments. We found that putative coronavirus remdesivir resistance-associated substitutions F480L and V570L—and naturally found polymorphisms A97V, P323L, and N491S, all in nsp12—did not decrease SARS-CoV-2 susceptibility to remdesivir. A nanoluciferase reporter clone with deletion of spike (S), envelope (E), and membrane (M) proteins exhibited high levels of transient replication, was inhibited by remdesivir, and therefore could function as an efficient non-infectious subgenomic replicon system. The developed SARS-CoV-2 reverse-genetics systems, including recombinants to modify infectious viruses and non-infectious subgenomic replicons with autonomous genomic RNA replication, will permit high-throughput cell culture studies—providing fundamental understanding of basic biology of this coronavirus. We have proven the utility of the systems in rapidly introducing mutations in nsp12 and studying their effect on the efficacy of remdesivir, which is used worldwide for the treatment of COVID-19. Our system provides a platform to effectively test the antiviral activity of drugs and the phenotype of SARS-CoV-2 mutants.

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector–mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

Background: Fine particulate matter (PM2.5) exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PM2.5on the pathology and airway hyperresponsiveness (AHR) of BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA) and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 (TIM-1) in this process. Methods: Forty female BALB/c mice were divided into four groups: control group, OVA group, OVA/PM group, and PM group (n = 10 in each group). Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PM2.5for 4 h per day and 5 days per week for a total of 8 weeks using a nose-only “PM2.5online enrichment system” in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PM2.5 online enrichment system only. AHR was detected. Bronchoalveolar lavage fluid (BALF) was collected for cell classification. The levels of interleukin-4 (IL-4), IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs. Results: The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups (P < 0.05). AHR in the PM group was also considerably more severe than that in the control group (P < 0.05). The BALF of OVA/PM group (28.00 ± 6.08 vs. 12.33 ± 4.51, t = 4.631, P = 0.002) and PM group (29.00 ± 3.00 vs. 12.33 ± 4.51, t = 4.927, P = 0.001) had more lymphocytes than the BALF of the control group. The number of neutrophils in the BALF of the OVA/PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) and PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) was much higher than those in the BALF of OVA group (P < 0.05). TUNEL assays showed that the number of apoptotic cells in the OVA/PM group was significantly higher than that in the OVA group (Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs. 0.51 ± 0.03, t = 8.094, P < 0.001) and PM group (Tunel IHS%, 1.20 ± 0.18 vs. 0.51 ± 0.09, t = 8.094, P < 0.001), and that the number of apoptotic cells in the PM group was significantly higher than that in the control group (Tunel IHS%, 0.51 ± 0.09 vs. 0.26 ± 0.03, t = 2.894, P = 0.020). The concentrations of IL-4 (77.44 ± 11.19 vs. 48.02 ± 10.02 pg/ml, t = 4.595, P = 0.002) and IL-5 (15.65 ± 1.19 vs. 12.35 ± 0.95 pg/ml, t = 3.806, P = 0.005) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.48 ± 0.10, t = 9.654, P < 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.40 ± 0.06, t = 6.818, P < 0.001) in the OVA/PM group were increased compared to those in the OVA group. The concentrations of IL-4 (77.44 ± 11.19 vs. 41.47 ± 3.40 pg/ml, t = 5.617, P = 0.001) and IL-5 (15.65 ± 1.19 vs. 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.97 ± 0.16, t = 5.000, P = 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.31 ± 0.06, t = 8.545, P < 0.001) in the OVA/PM group were increased compared to those in the PM group. The concentration of IL-4 (41.47 ± 3.40 vs. 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037) and the Bax/Bcl-2 ratio (0.97 ± 0.16 vs. 0.18 ± 0.03, t = 7.439, P < 0.001) and TIM-1/β-actin ratio (0.31 ± 0.06 vs. 0.02 ± 0.01, t = 5.109, P = 0.001) in the PM group were also higher than those in the control group. Conclusions: Exacerbated AHR associated with allergic asthma caused by PM2.5is related to increased apoptosis and TIM-1 activation. These data might provide insights into therapeutic targets for the treatment of acute exacerbations of asthma induced by PM2.5.

The asphalt core itself is a no-joint water barrier in embankment dams and is connected to the concrete plinth on the bottom of the core. A reliable asphalt core-plinth connection is crucial and must remain watertight when the core deforms due to deformations in the embankment and foundation and due to reservoir water pressure. A large number of tension tests were conducted to determine the best ratios, joint thickness and suitable additives for the sandy asphalt mastic (SAM) mix used for the connection. With the ratios of bitumen to filler to sand of 20%:35%:45% and by adding 4% SBS in the bitumen, one got a very suitable composition for the asphalt core-plinth connection in tensile conditions. Model tests were conducted to study the connection behavior when subjected to large shear displacements and high water pressure. The joint model test results indicate that the plane-surface plinth, curved-surface plinth, and plinth with or without copper water-stop showed no significant difference for the connection in the joint shear behavior. However, plinth with copper water-stop is suggested to enhance its tensile and shear behavior.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has demonstrated the value of pursuing different vaccine strategies. Vaccines based on whole viruses, a widely used vaccine technology, depend on efficient virus production. This study aimed to establish SARS-CoV-2 production in the scalable packed-bed CelCradleTM 500-AP bioreactor. CelCradleTM 500-AP bottles with 0.5 L working volume and 5.5 g BioNOC™ II carriers were seeded with 1.5 × 108 Vero (WHO) cells, approved for vaccine production, in animal component-free medium and infected at a multiplicity of infection of 0.006 at a total cell number of 2.2–2.5 × 109 cells/bottle seven days post cell seeding. Among several tested conditions, two harvests per day and a virus production temperature of 33 °C resulted in the highest virus yield with a peak SARS-CoV-2 infectivity titer of 7.3 log10 50% tissue culture infectious dose (TCID50)/mL at 72 h post-infection. Six harvests had titers of ≥6.5 log10 TCID50/mL, and a total of 10.5 log10 TCID50 were produced in ~5 L. While trypsin was reported to enhance virus spread in cell culture, addition of 0.5% recombinant trypsin after infection did not improve virus yields. Overall, we demonstrated successful animal component-free production of SARS-CoV-2 in well-characterized Vero (WHO) cells in a scalable packed-bed bioreactor.

Centrioles and cilia are microtubule-based structures of defined architecture, but what regulates this architecture is not clear. Here the authors discover that centrosomal-P4.1-associated-protein (CPAP) binds the α/β-tubulin dimer and licenses it for tubulin delivery contributing to centriolar/ciliary length and architecture control.

In this research, we investigated the electronic structure and optical property of new diluted magnetic semiconductor (Y0.75Sr0.25) (Cu0.75Mn0.25)SO with decoupled charge and spin doping by first-principle calculation. We also compared (Y0.75Sr0.25) (Cu0.75Mn0.25)SO with pure YCuSO, and found that (Y0.75Sr0.25) (Cu0.75Mn0.25)SO is still a direct semiconductor with a band gap 1.20eV. The important difference from YCuSO is that the DOS of (Y0.75Sr0.25) (Cu0.75Mn0.25)SO presents asymmetry around fermi surface, leading to obvious spin order and ferror-magnetism due to the p-d hybridization through Mn 3d and S 3p. In case of the optical properties (including reflectivity coefficient, absorption coefficient, the imaginary part and real part of complex dielectric constant), the intensity of all peaks for both pure and doped YCuSO tends to zero above 15.5eV. However, the value of all the peaks for (Y0.75Sr0.25) (Cu0.75Mn0.25)SO reduces to some extent due to the Sr and Mn dopant. In addition, the position of all the peaks for (Y0.75Sr0.25) (Cu0.75Mn0.25)SO have a “red shift”, probably originating from the impurity states generated by the p-d hybridization through Mn 3d and S 3p. This will be beneficial for searching new 1111 phase DMS.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.