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Introduction: The disconnected-interacting protein 2 homolog A (DIP2A), a member of disconnected-interacting 2 protein family, has been shown to be involved in human nervous system-related mental illness. This protein is highly expressed in the nervous system of mouse. Mutation of mouse DIP2A causes defects in spine morphology and synaptic transmission, autism-like behaviors, and defective social novelty [5,27], indicating that DIP2A is critical to the maintenance of neural development. However, the role of DIP2A in neural differentiation has yet to be investigated. Objective: To determine the role of DIP2A in neural differentiation, a neural differentiation model was established using mouse embryonic stem cells (mESCs) and studied by using gene-knockout technology and RNA-sequencing-based transcriptome analysis. Results: We found that DIP2A is not required for mESCs pluripotency maintenance, but loss of DIP2A causes the neural differentiation abnormalities in both N2B27 and KSR medium. Functional knockout of Dip2a gene also decreased proliferation of mESCs by perturbation of the cell cycle and profoundly inhibited the expression of a large number of neural development-associated genes which mainly enriched in spinal cord development and postsynapse assembly. Conclusions: The results of this report demonstrate that DIP2A plays an essential role in regulating differentiation of mESCs towards the neural fate.

Abstract Background Autologous mesenchymal stem cells (MSCs) have emerged as a therapeutic option for many diseases. Hypertensive kidney disease (HKD) might impair MSCs’ reparative ability by altering the biomolecular properties, but the characteristics of this impairment are unclear. In our previous pre-clinical studies, we found hypoxic preconditioning (HPC) enhanced angiogenesis and suppressed senescence gene expression. Thus, we hypothesize that HPC would improve human MSCs by enhancing their functionality and angiogenesis, creating an anti-inflammatory and anti-senescence environment. Methods MSC samples (n = 12 each) were collected from the abdominal fat of healthy kidney donors (HC), hypertensive patients (HTN), and patients with hypertensive kidney disease (HKD). MSCs were harvested and cultured in Normoxic (20% O2) or Hypoxic (1% O2) conditions. MSC functionality was measured by proliferation assays and cytokine released in conditioned media. Senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) activity. Additionally, transcriptome analysis using RNA-sequencing and quantitative PCR (qPCR) were performed. Results At baseline, normoxic HTN-MSCs had higher proliferation capacity compared to HC. However, HPC augmented proliferation in HC. HPC did not affect the release of pro-angiogenic protein VEGF, but increased EGF in HC-MSC, and decreased HGF in HC and HKD MSCs. Under HPC, SA-β-gal activity tended to decrease, particularly in HC group. HPC upregulated mostly the pro-angiogenic and inflammatory genes in HC and HKD and a few senescence genes in HKD. Conclusions HPC has a more favorable functional effect on HC- than on HKD-MSC, reflected in increased proliferation and EGF release, and modest decrease in senescence, whereas it has little effect on HTN or HKD MSCs.

Abstract Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.

To explain the moisture adsorption properties and improve the package material of polydextrose product, the adsorption and desorption isotherms of five domestic samples with initial moisture content (IMC) of 1.01%~4.89% were determined in this study in the range of 20~35 ℃ and ERH10%~90% using a dynamic water sorption analyzer. The adsorption and desorption isotherms were sigmoidal-shaped curves, and there was a hysteresis between desorption isotherm and the adsorption isotherm when ERH was less than 80%. Because polydextrose is an amorphous phase powder, we assumed that the water adsorption process of polydextrose was an equilibrium that existed among the vapor phase, the liquid phase (polylayer adsorption) and the solid solution (monolayer adsorption), and the adsorptive and desorptive sigmoidal-shaped isotherms can be de-convolved into a monolayer (Mh) and a polylayer component (Md) in accordance with Hailwood- Horrobin (HH) model. The polylayer water content of adsorption and desorption showed a sigmoidal increase with increasing ERH. The monolayer water content of desorption remained constant with increasing ERH, while that of the adsorption increased slowly for samples a1 to a4 with IMC 4.87% to 2.35% and decreased almost linearly for sample a5 with IMC 1.01%. As the IMCs of the samples decreased, the molecular weight of the polymer at the sorption site was maximum for sample a1 and minimum for sample a5. Although the FTIR showed the smallest intensity of hydroxyl group (3 416 cm–1) and amorphous structural functional group (1 027 cm–1) for a5 sample, a5 sample had the largest moisture absorption rate. These results suggested that, for the lower moisture content of polydextrose samples processed by different processes, their adsorptive monolayer water content seemed to decrease almost linearly with an increase of ERH. However their adsorptive polylayer water content sigmoidally increased with an increase of ERH, and their moisture absorption rate and hygroscopic capacity increased.

For seeking the cause of the increase in dough water absorption rate after cold plasma treatment, this study adopted low-pressure, radiofrequency 120 W helium cold plasma (CP) to treat wheat flours from 0 s to 180 s. Results showed that water absorption rate, conductivity, values of water and sucrose solvent retention capacity (SRC), and paste breakdown value in wheat flours increased significantly with increasing CP treatment time. To further explore the change causes in these physiochemical indexes, we developed a seven- parameter polynomial , (M was equilibrium moisture (%), ERH was equilibrium relative humidity (decimal), t was temperature (℃), and A~G were parameters. This polynomial could fit moisture sorption isotherms (20-35 ℃ and ERH 10%-90%) of helium CP treated flours, and the goodness-of-fit indexes were superior to those of modified Chung-Pfost (commonly used) and four-parameter polynomial (without temperature term) equations. The seven-parameter polynomial equation clearly showed the hysteresis loops between moisture adsorption and desorption isotherms of flour samples, which shifted downward with increasing temperature. The hysteresis degree showed a parabolic shape curve with increasing ERH, and the vertex of the parabola was at the range of 40-50% ERH. CP treatment shifted the monolayer adsorption sites to multi-molecular adsorption sites ahead of schedule, from ERH 50% to 40%. Further analysis using Dent model showed that the helium CP treatment was able to reduce the mono-layer moisture content and spreading pressure in wheat flour, and increase the elasticity of a capillary wall. The ability of water molecules was increased to form hydrogen bonds with the chemical components, which promoted the uniform distribution and permeation of water molecules into flour particles. Infrared spectral scanning showed that the degree of short-range order at the surface of starch granules and the interaction between protein and starch tended to increase with increasing CP time. Helium cold plasma technology has potential application in improving flour processing quality.

Abstract For decades, studies on learner emotions in foreign language learning have been predominantly focused on foreign language anxiety, and recent years have witnessed a surge in the exploration of other positive and negative emotions such as enjoyment and boredom. The current study aimed to extend this line of inquiry and explored the bidirectional relations between foreign language achievements and learner emotions through a questionnaire study among English learners (n = 756) in Chinese senior secondary schools, an understudied population in foreign language emotion research. Results indicated that the three emotions were significantly related to each other. Further analyses suggested that anxiety and boredom were significant predictors of achievements, and that language achievements predicated all the three emotions. The study confirms the reciprocal relationships between language achievements and emotions and provides pedagogical implications for language teaching.

Abstract Background The timing of treating cancer patients is an essential factor in the efficacy of treatment. So, patients who will not respond to current therapy should receive a different treatment as early as possible. Machine learning models can be built to classify responders and nonresponders. Such classification models predict the probability of a patient being a responder. Most methods use a probability threshold of 0.5 to convert the probabilities into binary group membership. However, the cutoff of 0.5 is not always the optimal choice. Methods In this study, we propose a novel data-driven approach to select a better cutoff value based on the optimal cross-validation technique. To illustrate our novel method, we applied it to three clinical trial datasets of small-cell lung cancer patients. We used two different datasets to build a scoring system to segment patients. Then the models were applied to segment patients into the test data. Results We found that, in test data, the predicted responders and non-responders had significantly different long-term survival outcomes. Our proposed novel method segments patients better than the standard approach using a cutoff of 0.5. Comparing clinical outcomes of responders versus non-responders, our novel method had a p-value of 0.009 with a hazard ratio of 0.668 for grouping patients using the Cox proportion hazard model and a p-value of 0.011 using the accelerated failure time model which approved a significant difference between responders and non-responders. In contrast, the standard approach had a p-value of 0.194 with a hazard ratio of 0.823 using the Cox proportion hazard model and a p-value of 0.240 using the accelerated failure time model indicating the responders and non-responders do not differ significantly in survival. Conclusion In summary, our novel prediction method can successfully segment new patients into responders and non-responders. Clinicians can use our prediction to decide if a patient should receive a different treatment or stay with the current treatment.

The traditional single nucleotide polymorphism (SNP)-wise approach in genome-wide association studies is focused on examining the marginal association between each SNP with the outcome separately and applying multiple testing adjustments to the resulting p-values to reduce false positives. However, the approach suffers a lack of power in identifying biomarkers. We design an ensemble machine learning approach to aggregate results from logistic regression models based on multiple subsamples, which helps to identify biomarkers from high-dimensional genomic data. We use different methods to analyze a genome-wide association study from the Alzheimer’s Disease Neuroimaging Initiative. The SNP-wise approach does not identify any significant signal, while our novel approach provides a list of ranked SNPs associated with the cognitive functions of interests.

To understand the cause for the increasing water absorption rate of wheat shorts after cold plasma treatment, a dynamic moisture adsorption instrument was used to measure the moisture sorption isotherms of samples treated with 120 W low-pressure strong radio frequency helium or oxygen CP for different times. The result was that the Caurie equation can fit an isotherm, and its coefficient C0 gived the density of water adsorbed by the sample. For adsorbed or desorbed samples, as the helium or oxygen CP treatment time at the same power increased, there was no difference in the density of adsorbed water, and the coefficient M0 gived the adsorbed water content of the monomolecular layer of the sample. For adsorbed or desorbed samples, as the helium CP treatment time at the same power increased, the water content of the monomolecular layer increased significantly. For samples treated with oxygen plasma, the content of the adsorbed monomolecular layer water first decreased and then increased as the treatment time increased, while the desorbed single-molecule water content showed a decreasing trend with the increased time. In order to improve the fitting of the Caurie equation, M0 was corrected to A+Bt (t was the temperature, A and B were constants). Analysis of the coefficients of the modified Caurie equation showed that as the 120 W helium CP treatment time (0~180 s) increased, the monomolecular layer of water, the number of adsorbed water molecule layers, the bound water content, and the water adsorption surface area all showed a continuous increase trend. For oxygen CP, these indicators showed an increasing trend in the first 60 s of processing, and then showed a decreasing trend if the processing time was extended. The results showed that compared with oxygen-cold plasma, high-energy helium-cold plasma improved the hydrophilicity of wheat shorts proteins and polysaccharides. As the treatment time increased, the surface area and number of layers of water adsorbed by these macromolecules and the monomolecular layer, and the bound water content steadily continued to increase.

Avihepadnavirus is a genus of the Hepadnaviridae family. It primarily infects birds, including species of duck, geese, cranes, storks, and herons etc. To understand the genetic relatedness and evolutionary diversity among avihepadnavirus strains, a comprehensive analysis of the available 136 full-length viral genomes (n = 136) was conducted. The genomes were classified into two major genotypes, i.e., GI and GII. GI viruses were further classified into 8 sub-genotypes including DHBV-I (duck hepatitis B virus-I), DHBV-II (Snow goose Hepatitis B, SGHBV), DHBV-III, RGHBV (rossgoose hepatitis B virus), CHBV (crane hepatitis B virus), THBV (Tinamou hepatitis B virus), STHBV (stork hepatitis B virus), and HHBV (Heron hepatitis B virus). DHBV-I contains two sub-clades DHBV-Ia and DHBV-Ib. Parrot hepatitis B virus (PHBV) stains fall into GII which appeared as a separate phylogenetic branch/clade. All the subtypes of viruses in GI and GII seem to be genetically connected with viruses of DHBV-I by multiple mutational steps in phylogeographic analysis. Furthermore, 16 potential recombination events among different sub-genotypes in GI and one in GII were identified, but none of which is inter-genotypic between GI and GII. Overall, the results provide a whole picture of the genetic relatedness of avihepadnavirus strains, which may assist in the surveillance of virus spreading.

Summary: The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303. FX1-5303 was used as a chemical probe to study the USP7-mediated regulation of p53 signaling in cells. It demonstrates mechanistic differences compared to MDM2 antagonists, a related class of anti-tumor agents that act along the same pathway. FX1-5303 synergizes with the clinically approved BCL2 inhibitor venetoclax in acute myeloid leukemia (AML) cell lines and ex vivo patient samples and leads to strong tumor growth inhibition in in vivo mouse xenograft models of multiple myeloma and AML. This work introduces new USP7 inhibitors, differentiates their mechanism of action from MDM2 inhibition, and identifies specific opportunities for their use in the treatment of AML.

The low-pressure radio-frequency (RF) cold plasma equipment has been developing in China for over 20 years. This equipment can significantly shorten rice cooking time and increase the solid solubility in the porridge. The safety evaluation of cold plasma technology in food industry is being carried out during the recent five years. This study measured the moisture desorption/adsorption isotherms of milled rice treated zero to four times by 120 W-20 s helium cold plasma (CP, 140 Pa, 13.56 MHz, the distance from plasma resource to the samples is 3 cm, 300 g samples were treated each time). In the range of 5 to 45 ℃ and 10% to 90% RH, in contrast to the untreated samples, CP repeat treatments did not change the hygroscopic properties such as monolayer and multilayer moisture properties and the moisture content of safe storage, but they increased hydrophilicity and water absorption rate of milled rice with a significant decrease in water contract angle. This study gives basic data for the safe storage of CP-treated milled rice.

Optical vortices (OVs), as eigenmodes of optical orbital angular momentum, have been widely used in particle micro-manipulation. Recently, perfect optical vortices (POVs), a subclass of OVs, are gaining increasing interest and becoming an indispensable tool in optical trapping due to their unique property of topological charge-independent vortex radius. Here, we expand the concept of POVs by proposing concentric ring optical traps (CROTs) and apply them to trapping and rotating particles. A CROT consists of a series of concentric rings, each being a vortex whose radius and topological charge can be controlled independently with respect to the other rings. Quantitative results show that the generated CROTs have weak sidelobes, good uniformity, and relatively high diffraction efficiency. In experiments, CROTs are observed to trap multiple dielectric particles simultaneously on different rings and rotate these particles with the direction and speed of rotation depending on the topological charge sign and value of each individual ring. In addition, gold particles are observed to be trapped and rotate in the dark region between two bright rings. As a novel tool, CROTs may find potential applications in fields like optical manipulation and microfluidic viscosity measurements.

Objective: The purpose of the study was to investigate the antibacterial mechanical properties of PLA nanofiber film loaded with PAE and its preservation effect on chilled mutton. Methods: By loading different amount (0, 12.5, 25, 50, 100 μL/20 mL) of electrospinning solution perillaldehyde (PAE) in polylactic acid (PLA) matrix, the antibacterial nanofiber film packaging with certain water absorption properties was prepared through electrospinning technology. The appearance and mechanical properties of PAE-PLA packaging film and physical-chemical indexes of mutton during preservation were analyzed via scanning electron microscopy and electronic universal testing machine. Results: With the increase of loading amount of PAE amount, the diameter, breaking elongation and tensile strength of PAE-PLA nanofiber films increased first and then decreased, which indicated that the addition of PAE can change the surface charge density of electrospinning solution. Therefore, the diameter of nanofibers was affected, and thereby the breaking elongation and tensile strength of nanofiber packaging films were changed. When the added PAE concentration was 50 μL/20 mL of electrospinning solution, the PAE-PLA nanofiber films showed uniform distribution, a largest diameter (370 nm) with good mechanical properties, i.e., elongation at break of 68.72% and tensile strength of 1.80 MPa. After 12 days of storage, the total bacterial count and volatile salt nitrogen of mutton packaged with PLA membrane loaded with 50 μL PAE were 5.52 lg(CFU/g) and 12.55 mg/100 g, respectively, which are significantly lower than the critical values of fresh meat and spoilage meat [6.0 lg(CFU/g) and 15.00 mg/100 g] (P＜0.05). Conclusion: PAE-PLA film loaded with 50 μL /20 mL PAE solution has good mechanical properties and antibacterial properties.

The business environment is the starting point and foothold of industrial upgrading, and it is also an important driving force for industrial upgrading. This paper is based on the investment and financing perspective to study the optimization of the business environment in the area of industrial upgrading to promote and promote the role of the two so as to achieve the effect of synergistic development of the two studies were constructed in the area business environment and industrial upgrading index system, and in the entropy weighting method of the indicator assignment, selected the relevant regional research data, through the linear weighting method to measure the level of development of the two. Empirical testing of the influence of the business environment on industrial upgrading is conducted by selecting the fixed-effect model, and investment and financing are added as an intermediary variable in the benchmark model. Finally, according to the empirical study of the impact of the business environment on industrial upgrading, it is concluded that in the benchmark regression analysis, with the introduction of control variables, the business environment shows a significant positive impact on industrial upgrading at least at the level of 10%. Meanwhile, investment and financing have an important mediating effect on the influence of the business environment on industrial upgrading.

[This corrects the article DOI: 10.1371/journal.pone.0287187.].

Based on the data of the State of Global Air (2020), air quality deterioration in Thailand has caused ~32,000 premature deaths, while the World Health Organization evaluated that air pollutants can decrease the life expectancy in the country by two years. PM2.5 was collected at three air quality observatory sites in Chiang-Mai, Bangkok, and Phuket, Thailand, from July 2020 to June 2021. The concentrations of 25 elements (Na, Mg, Al, Si, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Br, Sr, Ba, and Pb) were quantitatively characterised using energy-dispersive X-ray fluorescence spectrometry. Potential adverse health impacts of some element exposures from inhaling PM2.5 were estimated by employing the hazard quotient and excess lifetime cancer risk. Higher cancer risks were detected in PM2.5 samples collected at the sampling site in Bangkok, indicating that vehicle exhaust adversely impacts human health. Principal component analysis suggests that traffic emissions, crustal inputs coupled with maritime aerosols, and construction dust were the three main potential sources of PM2.5. Artificial neural networks underlined agricultural waste burning and relative humidity as two major factors controlling the air quality of Thailand.

Under the background of the development of new media technology, the attention of wushu events in the society is gradually increasing, which makes the competition in the event broadcasting market more and more intense. This paper focuses on the problem of predicting the operational risk of wushu event broadcasting rights, based on the GBRT algorithm, innovatively improves the traditional loss function, introduces the regular term, and proposes the application of XGBoost algorithm in the operational risk prediction of wushu event broadcasting rights. The improved algorithm divides the operational risk of broadcasting rights into two main levels, covering three primary and 10 secondary indicators. In this study, the XGBoost algorithm is applied in the early warning of informing proper operation risk, which is classified into two main levels, covering 3 primary and 10 secondary indicators. The article also conducts an in-depth experimental analysis of the risk of overpremium of the event rights and the risk of matching the audience’s demand. In addition, according to the results of audience analysis, men have become the primary audience of wushu events, with a frequency of up to 401 times. Based on the XGBoost algorithm, the wushu event broadcasting right operation risk warning system can effectively predict and help the event broadcasting platform to avoid the potential operation risk, which provides valuable data support for the market decision-making.

Abstract Background Disco-interacting protein 2 homolog B is a member of the Dip2 family encoded by the Dip2b gene. Dip2b is widely expressed in neuro-related tissues and is essential in axonal outgrowth during embryogenesis. Methods Dip2b knockout mouse embryonic stem cell line was established by CRISPR/Cas9 gene-editing technology. The commercial kits were utilized to detect cell cycle and growth rate. Flow cytometry, qRT-PCR, immunofluorescence, and RNA-seq were employed for phenotype and molecular mechanism assessment. Results Our results suggested that Dip2b is dispensable for the pluripotency maintenance of mESCs. Dip2b knockout could not alter the cell cycle and proliferation of mECSs, or the ability to differentiate into three germ layers in vitro. Furthermore, genes associated with axon guidance, channel activity, and synaptic membrane were significantly downregulated during neural differentiation upon Dip2b knockout. Conclusions Our results suggest that Dip2b plays an important role in neural differentiation, which will provide a valuable model for studying the exact mechanisms of Dip2b during neural differentiation.

Tumor Treating Fields (TTFields) is a non-invasive modality for cancer treatment that utilizes a specific sinusoidal electric field ranging from 100 kHz to 300 kHz, with an intensity of 1 V/cm to 3 V/cm. Its purpose is to inhibit cancer cell proliferation and induce cell death. Despite promising outcomes from clinical trials, TTFields have received FDA approval for the treatment of glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM). Nevertheless, global acceptance of TTFields remains limited. To enhance its clinical application in other types of cancer and gain a better understanding of its mechanisms of action, this review aims to summarize the current research status by examining existing literature on TTFields’ clinical trials and mechanism studies.

Recently, Abrantes et al [...]

A typical solid-state quantum sensor can be developed based on negatively charged nitrogen-vacancy (NV−) centers in diamond. The electron spin state of NV− can be controlled and read at room temperature. Through optical detection magnetic resonance (ODMR) technology, temperature measurement can be achieved at the nanoscale. The key to ODMR technology is to apply microwave resonance to manipulate the electron spin state of the NV−. Therefore, the microwave field characteristics formed near the NV− have a crucial impact on the sensitivity of ODMR measurement. This article mainly focuses on the temperature situation in cellular applications and simulates the influence of structural parameters of double open loop resonant (DOLR) microwave antennas and broadband large-area (BLA) microwave antennas on the microwave field’s resonance frequency, quality factor Q, magnetic field strength, uniformity, etc. The parameters are optimized to have sufficient bandwidth, high signal-to-noise ratio, low power loss, and high magnetic field strength in the temperature range of 36 °C to 42.5 °C. Finally, the ODMR spectra are used for effect comparison, and the signal-to-noise ratio and Q values of the ODMR spectra are compared when using different antennas. We have provided an optimization method for the design of microwave antennas and it is concluded that the DOLR microwave antenna is more suitable for living cell temperature measurement in the future.

Abstract Stress/force monitoring of prestressing tendons is challenging but crucial to the evaluation of the safety of structures in which they are used. To this end, a smart elasto-magneto-electric (EME) sensor based on elasto-magnetic (EM) and magneto-electric (ME) effects is proposed for noncontact field monitoring of the absolute stress in these steel tendons. In this paper, our research in design, implementation, and application of the EME sensory system for non-destructive monitoring of prestressing tendons is overviewed. The results confirm that the developed EME sensor possesses high repeatability, ease of operation and maintenance, corrosion resistance, and long expected service-life. It is demonstrated that the proposed EME sensory technology is feasible for the stress/force monitoring of prestressing tendons in both new and existing structures and the EME sensory system is reliable and stable.

A series of myricetin derivatives containing phenoxypyridine structure were designed and synthesized on the basis of the natural product myricitrin, which were structurally characterized on NMR and HRMS. The results of antiviral activity tests showed that some of the target compounds exhibited better inhibitory effects. Among them, B19 and B21 showed better curative activity with EC50 values of 195.67 and 173.64 μg/mL, respectively, which were superior to that of the control agent ningnanmycin(NNM) (238.30 μg/mL). B21 showed better protective activity with EC50 value of 236.37 μg/mL, which was better than that of the control agent NNM (269.89 μg/mL). The results of microcalorimetry showed that B1, B19 and B21 had good binding affinity with tobacco mosaic virus capsid protein (TMV-CP), and the Kd values were 0.059, 0.093 and 0.069 μM, which was higher than that of NNM (Kd = 2.78 μM). The molecular docking results showed that the hydrogen bond lengths between B1, B21 and the key amino acid residues of TMV-CP were shorter and with more tightly bound than those of NNM. In B21-treated tobacco leaves, chlorophyll content and superoxide dismutase (SOD) activity were significantly elevated, indicating that B21 can participate in regulating plant photosynthesis as well as defense enzymes and inducing plants to improve disease resistance.

Duck hepatitis A virus (DHAV) is one of key pathogens for duck viral hepatitis, especially in Asian duck industry. Currently, two main genotypes (DHAV-1 and -3) exist. To explore insightfully the evolutionary character, we assessed the available 141 full-length genome sequences of DHAV isolated in 1986–2020 globally and divided DHAV-1 and DHAV-3 into further seven (DHAV-1 a-g) and five (DHAV-3 a-e) sub-clades, respectively. Phylogenetic and phylogeographic network analyses indicated great genetic diversity of DHAV identified in China, where the DHAV-1 cluster and DHAV-3 cluster were linked by virus strain HDHV1-BJ (GenBank ID: FJ157172.1) and Du_CH_LSD_090612 (GenBank ID: JF828995.1) via a long mutational branch and intermediate strains. Several strains previously identified as DHAV-1 according to the partial gene sequences were actually clustered within DHAV-3 in full-length genome-based analysis. Furthermore, we identified 32 recombination events across virus genome with the recombination hotspot at the 5′ end and upstream of the capsid coding region. The highest variability of DHAV polyprotein was shown at the upstream region of the N terminus P-loop region, e.g., amino acids 672–716, followed by the aa 334–359 in the Capsid encoding region. The results presented here provides a robust insight into the genetic exchange patterns of DHAV genomes during the past decades, which may be used to map the evolutionary history and facilitate preventive measures of DHAVs.

Dementia is characterized as a decline in cognitive function, including memory, language and problem-solving abilities. In this paper, we conducted a Genome-Wide Association Study (GWAS) using data from the electronic Medical Records and Genomics (eMERGE) network. This study has two aims, (1) to investigate the genetic mechanism of dementia and (2) to discuss multiple p-value thresholds used to address multiple testing issues. Using the genome-wide significant threshold (p≤5×10−8), we identified four SNPs. Controlling the False Positive Rate (FDR) level below 0.05 leads to one extra SNP. Five SNPs that we found are also supported by QQ-plot comparing observed p-values with expected p-values. All these five SNPs belong to the TOMM40 gene on chromosome 19. Other published studies independently validate the relationship between TOMM40 and dementia. Some published studies use a relaxed threshold (p≤1×10−5) to discover SNPs when the statistical power is insufficient. This relaxed threshold is more powerful but cannot properly control false positives in multiple testing. We identified 13 SNPs using this threshold, which led to the discovery of extra genes (such as ATP10A-DT and PTPRM). Other published studies reported these genes as related to brain development or neuro-development, indicating these genes are potential novel genes for dementia. Those novel potential loci and genes may help identify targets for developing new therapies. However, we suggest using them with caution since they are discovered without proper false positive control.

Problems exist in power grid data management that have unclear relationships, weak security and low accuracy. By analysing the knowledge graph construction characteristics of smart grid data information and knowledge extraction, the grid data management platform is reshaped architecturally, and the knowledge graph construction technology is embedded in the grid data management framework. For the aforementioned problems, the knowledge graph construction and Internet of Things optimisation framework of power grid data knowledge extraction are proposed in this article. Firstly, the semantic search (KGSS) algorithm based on the knowledge graph is used. The KGSS algorithm extracts knowledge from structured, semi-structured and unstructured grid data through the massively parallel processing acquisition model and Hadoop database, and constructs knowledge entities, attributes and inter-entity relationships. Then, it optimises and predicts through the knowledge graph construction and Internet of Things optimisation framework extracted from power grid data knowledge. Finally, the experimental results show that the accuracy rate of the KGSS algorithm is 92%. The experimental results also show that it provides new ideas and research directions for power grid data under big data in the future.

Abstract Full electronic automation in stock exchanges has recently become popular, generating high-frequency intraday data and motivating the development of near real-time price forecasting methods. Machine learning algorithms are widely applied to mid-price stock predictions. Processing raw data as inputs for prediction models (e.g., data thinning and feature engineering) can primarily affect the performance of the prediction methods. However, researchers rarely discuss this topic. This motivated us to propose three novel modelling strategies for processing raw data. We illustrate how our novel modelling strategies improve forecasting performance by analyzing high-frequency data of the Dow Jones 30 component stocks. In these experiments, our strategies often lead to statistically significant improvement in predictions. The three strategies improve the F1 scores of the SVM models by 0.056, 0.087, and 0.016, respectively.

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People’s Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total “Infectome” was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.

The purpose of this paper is to explore the impact of the COVID-19 epidemic on global trade and its transformation of trade relations between the United States and China. The outbreak of the epidemic triggered a huge restructuring of the global trade system and accelerated the trend of global trade de-globalization. As the two largest economies, the trade relationship between the United States and China plays an important role in this process. This paper analyzes the causes of deglobalization, which are mainly caused by the fracture of industrial chain, trade protection and industrial upgrading. At the same time, the paper focuses on the factors that have caused the deglobalization trend in the post-COVID-19 era, such as changing trade agreements, poor cross-border investment environment, and the challenges and uncertainties brought by e-commerce. Finally, it concentrates on the changes of the US and China bilateral trade in the post-COVID-19 era. Affected by the epidemic, the bilateral relationship between these two countries has become more conflictual and focused on technological competition. Finally, the trend against globalization has led to inefficient economic development and the regionalization of trade because of the necessity of communication.

Microbial residue nitrogen can indicate soil quality and is crucial for soil nitrogen retention and supply. However, it is still unclear how the dynamic changes in soil microbial residue nitrogen affect crop nitrogen uptake in agricultural practice. Based on a long-term wheat-maize rotation experiment with different nitrogen application rates (150 kg N ha−1, 200 kg N ha−1, and 300 kg N ha−1), 15N-labeled nitrogen fertilizer was applied during the wheat season to track the dynamics of soil microbial residue nitrogen and its mediated fertilizer nitrogen. The results showed that nitrogen addition was beneficial to the accumulation of microbial residue nitrogen (mainly fungal microbial residue nitrogen). Its contribution rate to soil total nitrogen is 54.87–56.55%, and the fertilizer nitrogen allocated to it accounts for 27.10–47.50% of the remaining fertilizer nitrogen in the soil. Ultimately, 6.77–10.24% of the nitrogen fertilizer applied remained in the soil as microbial residue nitrogen. In addition, microbial residue nitrogen is mainly mineralized during the jointing and filling stages of wheat. In a word, the accumulation and mineralization of soil microbial residue nitrogen during the application of 200 kg N ha−1 better guaranteed the uptake of nitrogen by wheat, which provided a reliable basis for guiding farmland fertility improvement and nitrogen fertilizer reduction in the North China Plain.

Objective: To generalise the features of PANP in case of potential clinical and pathological pitfall of diagnosis. Methods: Thirteen patients diagnosed as PANP were retrospectively analyzed in the Pathology Department of Capital Medical University from August 2014 to December 2019. Immunohistochemical staining with CD34, CK, Vim, Calponin, Ki67, Bcl-2, and STAT-6 was performed with envision-two steps method. Results: PANP is a benign tumor presenting with gross variegated tan to gray soft fleshy tissue with foci of obvious hemorrhage and necrosis. The imaging shows internal heterogeneous hyperintensity with a peripheral hypointense rim while postcontrast images display a strong nodular and patchy enhancement. Vimentin (Vim) stain was consistently positive, while negative for CD34, STAT-6 and Bcl-2 (focal positive in two cases). Calponin and CK stain was positive in nine cases, respectively. Conclusion: PANP is a clinically rare tumor which may simulate malignancy lesion. Recognizing of characteristic features in these thirteen patients would be beneficial to avoid misdiagnosis and unnecessary aggressive treatment. Level of evidence: This work was Level 2 of evidence according to the Guide for Authors.

Inspired by the application of fungicide from natural products, a series of chalcone derivatives containing pyridazine were designed, synthesized, and evaluated for their antifungal activities against nine plant fungi and antibacterial activity against three plant bacteria. The antibacterial results revealed that B8 showed the best activity against Xanthomonas campestris pv. citri (Xac) with an EC50 value of 78.89 μg/mL, superior to Bismerthiazol (EC50 = 86.72 μg/mL). The antifungal bioactivity results showed that some of the compounds had good bioactivity against fungi, such as B4 showed the best bioactivity against Botrytis cinerea (BC) with an EC50 value of 8.91 μg/mL, which was better than the azoxystrobin (EC50 = 20.28 μg/mL). Compounds B4, D2 and D3 showed good biological activity against Rhizoctonia solani (RS), with an EC50 value of 18.10, 20.18 and 20.60 μg/mL, comparable to the azoxystrobin. Antifungal mechanism studies of BC by B4 suggest that B4 disrupts the cell membrane of the mycelium and thus inhibits the growth of the fungus. The above indicates that chalcone derivatives containing pyridazine have the potential to become fungicides.

Abstract The emergence and rapid spread of the acute respiratory syndrome coronavirus-2 have confirmed that animal coronaviruses represent a potential zoonotic source. Porcine deltacoronavirus is a worldwide evolving enteropathogen of swine, detected first in Hong Kong, China, before its global identification. Following the recent detection of PDCoV in humans, we attempted in this report to re-examine the status of PDCoV phylogenetic classification and evolutionary characteristics. A dataset of 166 complete PDCoV genomes was analyzed using the Maximum Likelihood method in IQ-TREE with the best-fitting model GTR + F + I + G4, revealing two major genogroups (GI and GII), with further seven and two sub-genogroups, (GI a-g) and (GII a-b), respectively. PDCoV strains collected in China exhibited the broadest genetic diversity, distributed in all subgenotypes. Thirty-one potential natural recombination events were identified, 19 of which occurred between China strains, and seven involved at least one China strain as a parental sequence. Importantly, we identified a human Haiti PDCoV strain as recombinant, alarming a possible future spillover that could become a critical threat to human health. The similarity and recombination analysis showed that PDCoV spike ORF is highly variable compared to ORFs encoding other structural proteins. Prediction of linear B cell epitopes of the spike glycoprotein and the 3D structural mapping of amino acid variations of two representative strains of GI and GII showed that the receptor-binding domain (RBD) of spike glycoprotein underwent a significant antigenic drift, suggesting its contribution in the genetic diversity and the wider spread of PDCoV.

Objective To investigate the changes of brain activation and brain network connectivity in patients with spinal cord injury (SCI). Methods A total of 20 patients with SCI were selected from Qilu Hospital of Shandong University from January to October 2021, including 8 patients with simple lower extremity involvement (paraplegia group) and 12 patients with all limbs involvement (tetraplegia group), and 10 healthy controls with matched baseline data with the SCI group were included in the same period. Functional near⁃infrared spectroscopy (fNIRS) was used to collect the data of cerebral oxyhemoglobin (HbO2) in the bilateral prefrontal lobe (LPFC/RPFC), motor cortex (LMC/RMC) and occipital lobe (LOL/ROL). The resting HbO2 β values was calculated by generalized linear model to evaluate the activation degree of the cerebral cortex covered by different detection channels, the correlation between HbO2 β values was calculated by Pearson correlation analysis and partial correlation to analysis different detection channels [partial correlation coefficient (r) was defined as functional connectivity strength] to evaluate the functional connectivity of the brain network. Results 1) Degree of brain activation: compared with the control group, the HbO2 β values corresponding to channel 2 (t=⁃2.482, P=0.020), channel 8 (t=⁃3.315, P=0.003) and channel 16 (t=⁃2.738, P=0.011) was increased in the tetraplegia group, while the HbO2 β value corresponding to channel 25 was decreased (t=2.104, P=0.045), and the HbO2 β value of channel 8 was increased (t=⁃2.475, P=0.020) in paraplegia group. Compared with the tetraplegia group, the HbO2 β values in channel 17 (t=2.552, P=0.017) and channel 25 (t=2.342, P=0.027) were increased in the paraplegia group. The value of HbO2 β in the left prefrontal lobe of tetraplegia group was significantly higher than that of control group (t=2.652, P=0.013). 2) The number of functional connections between different channels and cerebral cortex: the proportion of channels related to motor cortex in different groups was 94.12% in the paraplegia group (32/34), 82.76% in the tetraplegia group (24/29), and only 74.36% in the control group (29/39). 3) Functional connectivity strength in the brain: compared with the control group, the functional connectivity strength in the right motor area was weakened in both the paraplegia group (t=4.572, P=0.000) and the tetraplegia group (t=4.822, P=0.000). Conclusions There are abnormalities in resting brain activation and functional connectivity of brain network after SCI, which are manifested as local enhancement of spontaneous neural activity in some brain regions and abnormal functional connectivity in cerebral cortices and brain regions.

Mean corpuscular hemoglobin (MCH) is a common blood routine test index. To explore the relationship between MCH and length of hospital stay in patients with acute pancreatitis (AP), we included 273 patients with AP without coronary heart disease, diabetes, hypertension and anemia in this study. All data were separated into three groups according to the length of hospital stay. Gender (p = 0.017) and severity classification (p < 0.001) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant different among three groups (p = 0.009). Thus, all data were separated into two groups according to MCH level, and significant increases in the length of hospital stay were observed between two groups (p = 0.030). A positive correlation between length of hospital stay and MCH was observed (r = 0.172, p = 0.004). Multiple linear regression analysis showed that MCH was independent correlated with the length of hospital stay, no matter whether severity classification of AP was included (beta = 0.248, p < 0.001; beta = 0.212, p < 0.001). Our results demonstrated that the length of hospital stay was correlated with MCH level in patients with AP, and MCH level at admission may predict the length of hospital stay independent of severity classification in AP. These results may provide a potential evaluation basis for the management of patients with AP.

The late Miocene Tarim desert experienced periodic wetting and greening in eccentricity minimum and East Asian summer monsoon weakening

Enterovirus 71 (EV71) and coxsackievirus (CV-A16) are the major etiological agents of hand, foot and mouth disease (HFMD). This report reviewed the full-length genomic sequences of EV71 identified in different provinces of China between 1998 and 2019 (a total of 312) in addition to eight worldwide reference genomes to address the genomic evolution and genetic events. The main prevalent EV71 strians in China are C4 genotypes, co-circulating with a few A, B5, C1, and C2 subgenotypes. A new emerging subgenotype in China was identified and classified as B6 genotype. Phylogeographic analysis revealed multiple branches, where a Jiangsu strain 2006-52-9 (GenBank ID: KP266579.1) was linked to different subgenotypes through multiple long mutant branches, including the CV-A16 viruses through the A genotype. Furthermore, identification of 28 natural recombination events suggests that the emergence of new genotypes are associated with intratypic recombination involving EV71 strains and intertypic recombination between EV71 and CV-A16 strains. Compared with the structural proteins, the non-structural proteins of EV71 seem to be highly variable with the highest variable regions of peptidase C3 (3C protein), P2A, and the N-terminus of RNA-dependent RNA polymerase. This study updates the phylogenetic and phylogeographic information of EV71 and provides clues to the emergence of new genotypes of EV71 based on genetics.

IntroductionNewcastle Disease Virus (NDV) is a highly adaptable virus with large genetic diversity that has been widely studied for its oncolytic activities and potential as a vector vaccine. This study investigated the molecular characteristics of 517 complete NDV strains collected from 26 provinces across China between 1946-2020.MethodsHerein, phylogenetic, phylogeographic network, recombination, and amino acid variability analyses were performed to reveal the evolutionary characteristics of NDV in China.Results and discussionsPhylogenetic analysis revealed the existence of two major groups: GI, which comprises a single genotype Ib, and GII group encompassing eight genotypes (I, II, III, VI. VII. VIII, IX and XII). The Ib genotype is found to dominate China (34%), particularly South and East China, followed by VII (24%) and VI (22%). NDV strains from the two identified groups exhibited great dissimilarities at the nucleotide level of phosphoprotein (P), matrix protein (M), fusion protein (F), and haemagglutinin-neuraminidase (HN) genes. Consistently, the phylogeographic network analysis revealed two main Network Clusters linked to a possible ancestral node from Hunan (strain MH289846.1). Importantly, we identified 34 potential recombination events that involved mostly strains from VII and Ib genotypes. A recombinant of genotype XII isolated in 2019 seems to emerge newly in Southern China. Further, the vaccine strains are found to be highly involved in potential recombination. Therefore, since the influence of recombination on NDV virulence cannot be predicted, this report’s findings need to be considered for the security of NDV oncolytic application and the safety of NDV live attenuated vaccines.

Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that threatens animal health and remains elusive despite years of research efforts. The systematical analysis of all available full-length genomes of TGEVs (a total of 43) and porcine respiratory coronaviruses PRCVs (a total of 7) showed that TGEVs fell into two independent evolutionary phylogenetic clades, GI and GII. Viruses circulating in China (until 2021) clustered with the traditional or attenuated vaccine strains within the same evolutionary clades (GI). In contrast, viruses latterly isolated in the USA fell into GII clade. The viruses circulating in China have a lower similarity with that isolated latterly in the USA all through the viral genome. In addition, at least four potential genomic recombination events were identified, three of which occurred in GI clade and one in GII clade. TGEVs circulating in China are distinct from the viruses latterly isolated in the USA at either genomic nucleotide or antigenic levels. Genomic recombination serves as a factor driving the expansion of TGEV genomic diversity.

A series of myricetin derivatives containing amide and hydrazide were designed and synthesized. All the compounds were characterized by NMR and HRMS. Bioactivity test showed that some of the target compounds had excellent anti-tobacco mosaic virus (TMV) activity. In particular, the median effective concentration (EC50) values of the anti-TMV curative and protective activities of N-(2-(2-(2-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)acetyl)hydrazineyl)-2-oxoethyl)-4-(trifluoromethyl)benzamide (G9) were 202.3 and 164.0 μg/mL respectively, superior to ningnanmycin (329.1, 230.3 μg/mL). Microscale thermophoresis (MST) and molecular docking showed that G9 had an excellent binding affinity with tobacco mosaic virus coat protein (TMV-CP) (Kd = 0.158 ± 0.024 μM), which was better than that of ningnanmycin (Kd = 2.074 ± 0.818 μM). Moreover, there were many interaction forces between G9 and the key amino acid residues of TMV-CP. The chlorophyll content and peroxidase (POD) activity of tobacco leaves treated with G9 increased significantly, indicating that G9 could improve the photosynthesis of tobacco leaves and stimulate the resistance of tobacco leaves to TMV. The insecticidal activity of G9 against Mythimna separata (M. separate) was found to be 95.2% at 200 μg/mL, which was close to bufenozide (100%). The insecticidal activity of myricetin was significantly improved after the introduction of active groups of amide and hydrazide, which could be further explored.

Background: Macrophages and monocytes orchestrate inflammatory processes in the lungs. However, their role in the pathogenesis of chronic obstructive pulmonary disease (COPD), an inflammatory condition, is not well known. Here, we determined the characteristics of these cells in lungs of COPD patients and identified novel therapeutic targets. Methods: We analyzed the RNA sequencing (scRNA-seq) data of explanted human lung tissue from COPD (n = 18) and control (n = 28) lungs and found 16 transcriptionally distinct groups of macrophages and monocytes. We performed pathway and gene enrichment analyses to determine the characteristics of macrophages and monocytes from COPD (versus control) lungs and to identify the therapeutic targets, which were then validated using data from a randomized controlled trial of COPD patients (DISARM). Results: In the alveolar macrophages, 176 genes were differentially expressed (83 up- and 93 downregulated; Padj < 0.05, |log2FC| > 0.5) and were enriched in downstream biological processes predicted to cause poor lipid uptake and impaired cell activation, movement, and angiogenesis in COPD versus control lungs. Classical monocytes from COPD lungs harbored a differential gene set predicted to cause the activation, mobilization, and recruitment of cells and a hyperinflammatory response to influenza. In silico, the corticosteroid fluticasone propionate was one of the top compounds predicted to modulate the abnormal transcriptional profiles of these cells. In vivo, a fluticasone–salmeterol combination significantly modulated the gene expression profiles of bronchoalveolar lavage cells of COPD patients (p < 0.05). Conclusions: COPD lungs harbor transcriptionally distinct lung macrophages and monocytes, reflective of a dysfunctional and hyperinflammatory state. Inhaled corticosteroids and other compounds can modulate the transcriptomic profile of these cells in patients with COPD.

The microstructure and oxidation behaviour of the pure AlON ceramics and 8 wt.% SiC-AlON composite were investigated at 700-1500°C. With increasing oxidation temperature, the surface morphology of two ceramics showed a change from acicular to flaky-like and then to granular features. With the addition of nanosized SiC particles, the oxidation resistance of the ceramics was remarkably enhanced above 1100°C. This is attributed to the formation of a dense oxide layer composed of Al2O3, SiO2 and mullite, which could cover the whole matrix and suppress further penetration of oxygen. Due to the dense oxide layer, the oxidation kinetics of the 8 wt.% SiC-AlON composites conformed to a parabolic law, while that of the pure AlON conformed to a linear law. After oxidation at 1500 °C for 40 h, the weight gain of the 8 wt.% SiC-AlON composites was 3.07mg/cm2, which was only 22.5% of that of the pure AlON.

Chicken infectious anemia (CIA) is an immunosuppressive poultry disease that causes aplastic anemia, immunosuppression, growth retardation and lymphoid tissue atrophy in young chickens and is responsible for huge economic losses to the poultry industry worldwide. The disease is caused by the chicken anemia virus (CAV), which belongs to the genus Gyrovirus, family Anelloviridae. Herein, we analyzed the full-length genomes of 243 available CAV strains isolated during 1991–2020 and classified them into two major clades, GI and GII, divided into three and four sub-clades, GI a-c, and GII a-d, respectively. Moreover, the phylogeographic analysis revealed that the CAVs spread from Japan to China, China to Egypt and subsequently to other countries, following multiple mutational steps. In addition, we identified eleven recombination events within the coding and non-coding regions of CAV genomes, where the strains isolated in China were the most active and involved in ten of these events. Furthermore, the amino acids variability analysis indicated that the variability coefficient exceeded the estimation limit of 1.00 in VP1, VP2, and VP3 proteins coding regions, demonstrating substantial amino acid drift with the rise of new strains. The current study offers robust insights into the phylogenetic, phylogeographic and genetic diversity characteristics of CAV genomes that may provide valuable data to map the evolutionary history and facilitate preventive measures of CAVs.

ABSTRACT The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so‐called nonspecific/off‐target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk‐Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk‐Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk‐Cre expression at the single‐cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT‐nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT‐PCR. The results demonstrate that Ctsk‐Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk‐Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk‐Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Model tests were performed with different temperatures and soil stabilizers to investigate the effect of horizontal frost heave force on open tunnels in seasonal frozen regions. Experimental results show that the dissipation of the frost heave force accelerated with the increase in temperature, and the data indicate that compared with soil without stabilizers, the horizontal frost heave force decreased by 10% and 15% in soil with lignin fiber and Huaxia No. 1 soil stabilizer. It can be concluded that the inhibitory effect of Huaxia No. 1 soil stabilizer on frost heave force was more significant than that of lignin fiber. According to the test results, the relation expression between horizontal frost heave force and frost heave amount was fitted.

With the rapid development of global industrialization, the pollution of hexavalent chromium (Cr(Ⅵ)) in soil and groundwater has become increasingly serious. Field investigation and laboratory tests were carried out for the soil polluted by the chromium slag of a ferroalloy plant. The adsorption, infiltration and dispersion experiments were conducted to study the adsorption characteristics and migration mechanism of Cr(Ⅵ) in silty clay. A three-dimensional kinetic mathematical model of Cr(Ⅵ) migration considering convection-dispersion-adsorption was established. The migration and distribution characteristics of Cr(Ⅵ) in groundwater with the pollution source located upstream or downstream of the contaminated site were obtained using the numerical approach. Meanwhile, the effects of dispersity and distribution coefficient) on the spatial and temporal distribution of Cr(Ⅵ) were revealed. The experimental results show that the Langmuir isotherm model well fits the adsorption data of silty clay. The maximum adsorption capacity of silty clay for Cr(Ⅵ) was 466.6 mg/kg. The hydraulic conductivity of silty clay under the infiltration of distilled water and 160 mg/L Cr(Ⅵ) solution was 6.5×10–7–6.7×10–7 cm/s, while it increased to 4.4×10–6 cm/s under infiltration of Cr(Ⅵ) solution with a concentration of 1 000 mg/L. The hydrodynamic dispersion coefficient (D) of silty clay was 1.4×10–4 m2/d. The value of the retardation factor ( ) was found to be 4.2–10. The results of the numerical simulation indicated that when the downstream was contaminated by Cr(Ⅵ), there was still a risk of pollution in the upstream even if molecular diffusion was not considered. The degree of pollution depended on the dispersity of the aquifer. Considering the adsorption of Cr(Ⅵ) by the aquifer, the higher the soil distribution coefficient, the smaller was the distribution range of the Cr(Ⅵ) pollution plume. Therefore, the transformation processes such as Cr(Ⅵ) adsorption should be focused on when predicting the distribution of Cr(Ⅵ) in contaminated sites.

Accurate detection of SARS-CoV-2 neutralizing antibody (nAb) is critical for assessing the immunity levels after virus infection or vaccination. As fast, cost-effective alternatives to viral infection-based assays, competitive binding (CB) assays were developed to quantitate nAb by monitoring the ability of sera to inhibit the binding of viral spike (S) protein to the angiotensin converting enzyme 2 (ACE2) receptor. Herein, we established a bead-based flow cytometric CB assay and tested the detection performance of six combination models, i.e. immobilized ACE2 and soluble Fc-tagged S1 subunit of S protein (iACE2/S1-Fc), immobilized ACE2 and soluble Fc-tagged receptor binding domain (RBD) of S protein (iACE2/RBD-Fc), immobilized S1 and soluble Fc-tagged ACE2 (iS1/ACE2-Fc), immobilized S1 and soluble His-tagged ACE2 (iS1/ACE2-His), immobilized RBD and soluble Fc-tagged ACE2 (iRBD/ACE2-Fc), and immobilized RBD and soluble His-tagged ACE2 (iRBD/ACE2-His). Using SARS-CoV-2 monoclonal antibodies and sera of convalescent COVID-19 patients and vaccinated subjects, the combination models iACE2/RBD-Fc, iACE2/S1-Fc and iS1/ACE2-His were identified to be able to specifically detect SARS-CoV-2 nAb, among which iACE2/RBD-Fc model showed the highest sensitivity, superior to a commercial SARS-CoV-2 surrogate virus neutralization test (sVNT) ELISA kit. Further studies demonstrated that the sensitivity and specificity of CB assays were affected by the tag of ACE2, type of spike and method of measuring binding rate between ACE2 and spike. Moreover, the iACE2/RBD-Fc model showed good performance in detecting kinetic development of nAb against both the prototype SARS-CoV-2 strain and an omicron variant of SARS-CoV-2 in people immunized by an inactivated SARS-CoV-2 vaccine, and the results of iACE2/RBD-Fc model are correlated well with those of live virus-based and pseudovirus-based neutralization tests, demonstrating the potential to be developed into a highly sensitive, specific, versatile and high-throughput method for detecting SARS-CoV-2 nAb in clinical practice.