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Background Mendelian disorders of cornification (MeDOC) are a group of heterogeneous genodermatoses with different genetic bases. The pathogenesis of a substantial group of MeDOC remains to be elucidated. Objectives To identify a new causative gene and the pathogenesis of a previously undescribed autosomal-dominant cornification disorder. Methods Whole-exome sequencing was performed in three families with the novel cornification disorder to identify the disease-causing variants. As the variants were located around the signal peptide (SP) cleavage site of a kallikrein-related peptidase, SP cleavage, subcellular localization and extracellular secretion of the variants were evaluated in eukaryotic overexpression systems by Western blotting or immunocytochemistry. Then the trypsin-like and chymotrypsin-like proteolytic activity of the peptidase and degradation of its catalytic substrate were assayed using the patients’ stratum corneum (SC) samples. The morphology of the lamellar bodies and corneodesmosomes (CDs) in the patients’ SC was ultrastructurally examined. A mouse model harbouring the equivalent variant was constructed and evaluated histologically. Results We identified two heterozygous variants affecting Gly50 in kallikrein-related peptidase (KLK)11 in a familial case and two sporadic cases with the new disorder, which is characterized by early-onset ichthyosiform erythroderma or erythrokeratoderma. KLK11 belongs to the family of kallikrein-related peptidases participating in skin desquamation by decomposing CDs, a process essential for shedding of the SC. In vitro experiments demonstrated that the variants perturbed the SP cleavage of KLK11, leading to subcellular mislocalization and impaired extracellular secretion of the KLK11 Gly50Glu variant. Both trypsin-like and chymotrypsin-like proteolytic activities were significantly decreased in the patients’ SC samples. Reduced proteolysis of desmoglein 1 and delayed degeneration of CDs were detected in patients’ SC, indicating delayed skin desquamation. Consistently, the patients showed a thickened, dense SC, indicating abnormal skin desquamation. Mice harbouring the homozygous c.131G>A (p.Gly44Glu) Klk11 variant, which is equivalent to KLK11 c.149G>A (p.Gly50Glu) in humans, exhibited hyperkeratosis and abnormal desquamation, partially recapitulating the phenotype. Conclusions We provide evidence that variants at Gly50 affecting the SP cleavage of KLK11 cause a new autosomal-dominant cornification disorder with abnormal desquamation. Our findings highlight the essential role of KLKs in maintaining homeostasis of skin keratinization and desquamation.

To determine the stress and damage state of rock mass is important for many geotechnical engineering. To study the feasibility of resistivity measurement in characterizing the damage and stress state, the resistivity measurement, uniaxial compression test, and incremental loading-unloading compression test were carried out on granite samples with different porosities (induced by different treatment temperatures). Results show that the resistivity is very sensitive to thermal damage and mechanical damage during compression. The evolution of resistivity can not only quantify thermal damage but also clearly indicate the critical stress (crack closure stress and crack damage stress) and damage stage during compression. In addition, the resistivity evolution was quite different in the pore closure stage, elastic deformation stage, and unstable cracking stage during the loading-unloading process, which is useful in field stress and damage state identification for field monitoring. The conductive mechanism variation during compression was discussed using the Archie equation considering crack volume strain evolution during the mechanical damage process. Overall, the resistivity measurement holds great potential in geotechnical engineering for field monitoring.

Electrical resistivity tomography (ERT) is an important method for exploring oil and gas formations, mineral deposits, and groundwater resources. However, most ERT instruments have limitations such as complicated human���computer interaction, few measurement parameters, difficulties in remote monitoring, and lack of four-dimensional (4D) exploration functions. To overcome these limitations, in this study we proposed and developed software for a remote control 4D ERT system based on a cloud platform and Internet of Things (IoT) technology. Specifically, acquisition device control, channel and control, acquisition control, and remote monitoring systems were designed, with various modules being debugged and optimized multiple times. The system is equipped with a 4G module, through which the collected data are transmitted to the cloud platform to realize real-time, stable, and long-distance data acquisition and transmission. Furthermore, the system realizes remote monitoring, real-time measurement, and other functions via the cloud and IoT technology, thereby providing strong technical support for achieving 4D exploration. The developed system was empirically evaluated by applying it to explore the Gequ Landslide area in Jainca County, Qinghai Province, China. The exploration results indicate that the system software has stable functions and high intelligence; thus it satisfies the requirements for field exploration.

Due to the high toxicity and potential health risk of cadmium (Cd), the influencing effects of major factors (like pH, OM, and clay, etc.) on Cd bioaccumulation and transfer from soil to crop grains are highly concerned. Multiple linear regression models were usually applied in previous literature, but these linear models could not reflect the threshold effects of major factors on Cd transfer under different soil environmental conditions. Soil pH and other factors on Cd transfer in a soil–plant system might pose different or even contrary effects under different soil Cd exposure levels. For this purpose, we try to apply a threshold regression model to analyze the effects of key soil parameters on Cd bioaccumulation and transfer from soil to wheat. The results showed that under different soil pH or Cd levels, several factors, including soil pH, organic matter, exchangeable Cd, clay, P, Zn, and Ca showed obvious threshold effects, and caused different or even contrary impacts on Cd bioaccumulation in wheat grains. Notably, the increase of soil pH inhibited Cd accumulation when pH > 7.98, but had a promotional effect when pH ≤ 7.98. Thus, threshold regression analysis could provide a new insight that can lead to a more integrated understanding of the relevant factors on Cd accumulation and transfer from soil to wheat. In addition, it might give us a new thought on setting regulatory limits on Cd contents in wheat grains, or the inhibitory factors of Cd transfer.

The high-density electrical method is a primary method used in shallow geophysical prospecting. Due to the rapid industrial development that has taken place in recent years, the function and performance of high-density electrical instruments have been considerably improved in several aspects. However, most of the electrical instruments currently available on the market still exhibit some shortcomings, such as being bulky, heavy, limited in their data acquisition accuracy, and difficult to connect to the Internet for remote monitoring. To address these problems, this study developed a new multifunctional four-dimensional (4D) high-density electrical instrument based on remote wireless communication technology. The system is small and lightweight, includes an integrated transceiver, has high data acquisition accuracy, and is capable of remote wireless real-time control. In this study, the hardware circuit was designed. The Arm all-in-one (AIO) LJD-eWinV5-ST7 with a 154.4 cm × 87 cm, 800 × 480 high-brightness wide-temperature-range display is used as the host computer, which has the advantages of small size, low power consumption, and abundant hardware resources. Internet of things (IoT) technology is incorporated in the system, and a 4G module is employed to provide a real-time remote control and data acquisition monitoring system based on the cloud platform. Tests showed that this instrument is stable and convenient to use and can meet the requirements for use in field prospecting.

A common approach to ocean current measurement is to use a motion-induced electric field; this is the basic principle of the expendable current profiler (XCP). However, existing studies into XCPs have not explored indoor simulations of the ocean current environment or the implementation of attitude correction in the hardware. The accuracy of XCPs can be verified via indoor experiments and is affected by the sinking attitude. Therefore, in this study, we develop an XCP to measure ocean information in real time, and we correct the data for different XCP sinking attitudes. Furthermore, we design electromagnetic-induction-based laboratory measurements of simulated dynamic ocean currents. The signals collected by the XCP are linearly related to the copper-plated-power-supply signal. The processed data are compared and the feasibility of extracting ocean current signals via electrodes is verified through laboratory simulations of XCPs. Furthermore, we performed marine experiments in the South China Sea; the results indicate that the system is stable and easy to use. We implemented an expendable conductivity-temperature-depth system at the same location; the curve trends measured by the two probes were consistent, and the maximum error was found to be 0.5 °C. We expect this work to improve the quality of ocean current measurements and subsequent monitoring capabilities.

Health risks caused by arsenic (As) contamination in soils and its migration in environmental media have attracted much attention. In this study, suburban farmland of KF city in the ecotone of the Yellow River and Huaihe River Basin was taken as the research area. A series of samples including topsoils (246), profile soils (280), matched wheat grains (22 groups), groundwater (26) and human hair (355) were collected. As distribution and transfer in soil-groundwater-wheat-hair (SGWH) system in typical sites were explored, and comprehensive health risk of As in SGWH system was assessed based on US EPA model and local exposure parameters. The results showed that spatial distribution of total As presented a significant high value area, and higher As contents (in the range of 0.45-29.86 mg kg

Quantitative identification of heavy metals (HM) sources in soils is key to prevention and control of heavy metal pollution. In this study, UNMIX, PMF (Positive matrix factorization) model and Pb-Zn-Cu isotopic compositions were combined to quantitatively identify heavy metal sources in a suburban agricultural area of Kaifeng, China. Using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) and ICP-MS, we measured Pb, Zn and Cu stable isotopic compositions, HM concentrations and HM chemical fractions in studied soils, as well as potential sources around the highly polluted site, including total suspended particle, compound fertilizer, irrigated river water and sediments. The results showed that total contents and chemical fractions of heavy metals, as well as Pb-Zn-Cu isotopic compositions presented great variation in different sites, which implied that heavy metal accumulation was obviously affected by local anthropogenic pollution source. UNMIX and PMF presented good agreement on source apportionment that industrial and agricultural activities (61.74% and 60.75% for UNMIX and PMF, respectively) were the major contributors to heavy metal accumulation in the study area. Especially, sewage irrigation and atmosphere deposition accounted for a large proportion (28.14% and 41.03% for UNMIX and PMF, respectively). Moreover, isotopic compositions of Pb, Zn and Cu in highly polluted soils and environment media gave further confirmation that sewage irrigation and atmosphere deposition were primary anthropogenic source. Therefore, combination of UNMIX, PMF model and Pb-Zn-Cu isotopic compositions showed good coordination in quantitative and specific source identification of heavy metals in agricultural soils.

In this paper, a speed-adjustable asynchronous condenser with AC excitation and its excitation control strategy are proposed. Through excitation control, the asynchronous condenser not only can adjust the voltage by reactive power output but also can adjust the speed to release rotational kinetic energy and increase the system inertia to smooth system frequency. In this paper, the model of the asynchronous condenser is established, and then a transiently improved control strategy for the asynchronous condenser considering the change of the stator excitation current, is proposed. It is verified by simulation that after the transient improvement control strategy is adopted, the asynchronous condenser can provide reactive power support and a certain frequency support capability to the system.

Background CLOVES syndrome (OMIM# 612918) is a rare overgrowth disorder resulted from mosaic gain-of-function mutations in the PIK3CA gene. All the reported CLOVES-associated PIK3CA mutations are missense mutations affecting certain residues. We aim to investigate underlying mutation and its pathogenicity in a patient with CLOVES syndrome and to evaluate the inhibitory effects of the PI3K/AKT/mTOR pathway inhibitors. Results We performed whole-exome sequencing (WES) and Sanger sequencing to detect underlying somatic mutations in the skin lesion of the patient. Quantitative real-time PCR (qRT-PCR) was employed to evaluate the mRNA abundance of PIK3CA in the patient’s skin lesion. AKT phosphorylation level assessed by immunoblotting of lysates from transiently transfected cells was performed to evaluate the PIK3CA mutations and inhibitory effects of PI3K/AKT/mTOR pathway inhibitors. A somatic frameshift mutation c.3206_3207insG (p.X1069Trpfs*4) in PIK3CA was identified in the genomic DNA extracted from the vascular malformation sample of the patient. This mutation affects the canonical stop codon of PIK3CA (NM_006218.4) and is predicted to produce a prolonged protein with four additional residues. qRT-PCR demonstrated that the mRNA expression levels of the patient’s affected skin tissue were comparable compared to the normal control. In vitro studies revealed that p.X1069Trpfs*4 mutant exhibited increased AKT phosphorylation significantly to that of the wildtype, which could be inhibited by PI3K/AKT/mTOR pathway inhibitors. Conclusions We have identified the first frameshift mutation in PIK3CA that causes CLOVES syndrome, which was confirmed to overactive PI3K/AKT/mTOR pathway by transient transfection assays. We also provided more evidence of ARQ092 to be a potential therapeutic option for PROS in vitro.

The high-density electrical method is a primary method used in shallow geophysical prospecting. With the rapid industrial development of recent years, the function and performance of high-density electrical instruments have been considerably improved in several aspects. However, most of the electrical instruments currently available on the market still exhibit some shortcomings, such as being bulky, heavy, limited in their data acquisition accuracy, and difficult to connect to the Internet for remote monitoring. To address these problems, this study developed a new multifunctional 4-dimensional (4D) high-density electrical instrument based on remote wireless communication technology. The system is small and lightweight, includes an integrated transceiver, has high data acquisition accuracy, and is capable of remote wireless real-time control. In this study, the hardware circuit was designed. The Arm all-in-one (AIO) LJD-eWinV5-ST7 with a 154.4 cm × 87 cm, 800 × 480 high-brightness wide-temperature-range display is used as the host computer, which has the advantages of small size, low power consumption, and abundant hardware resources. IoT technology is incorporated in the system, and a 4G module is employed to provide a real-time remote control and data acquisition monitoring system based on the cloud platform. Tests showed that this instrument is stable and convenient to use and can meet the requirements for use in field prospecting.

BackgroundCLOVES syndrome(OMIM#612918) is a rare overgrowth disorder resulted from mosaic gain-of-function mutations in the PIK3CA gene. All the reported CLOVES-associated PIK3CA mutations are missense mutations affecting certain residues. To investigate underlying mutation and its pathogenicity in a patient with CLOVES syndrome and to evaluate the inhibitory effect of ARQ092, one of the PI3K/AKT/mTOR pathway inhibitors. ResultsWe performed whole-exome sequencing (WES) and Sanger sequencing to detect underlying somatic mutations in the skin lesion of the patient. Quantitative real-time PCR (qRT-PCR) was employed to evaluate the mRNA abundance of PIK3CA in the patient’s skin lesion. AKT phosphorylation level assessed by Western blot was performed to evaluate the PIK3CA mutations and inhibitory effects of ARQ092. A novel somatic frameshift mutation c.3206_3207insG (p.X1069Trpfs*4) in PIK3CA was identified in the genomic DNA extracted from the vascular malformation sample of the patient. This mutation affects the canonical stop codon of PIK3CA (NM_006218.4 ) and is predicted to produce a prolonged protein with four additional residues. qRT-PCR demonstrated that the mRNA expression levels of the patient’s affected skin tissue were comparable compared to the normal control. In vitro studies revealed that p.X1069Trpfs*4 mutant exhibited increased AKT phosphorylation significantly compared to that of the wildtype, which could be inhibited by ARQ092. ConclusionsWe have identified the first frameshift mutation in PIK3CA, which overactivated PI3K/AKT/mTOR pathway to cause CLOVES syndrome. We also provided evidence of ARQ092 to be a potential therapeutic option for PROS in vitro.

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.

Water and salt transfer coupled with phase change may cause serious damage to engineering structures in saline soil regions. In this study, the migration of water and salt in silty clay collected from the Qinghai-Tibet Plateau is explored experimentally and numerically during freezing and thawing processes. The results revealed that there are significant differences in the variations of liquid water content and solution concentration for different initial salt contents, due to salt crystallization and dissolution. The temperature-induced water migration is determined by the soil properties, which can be well explained by the thermodynamics of mass transfer. The amount of salt migrated upward during cooling is slightly larger than that transported downward in the warming period, implying that salt may be accumulated in the surface soil after a large number of circulations and finally result in soil salinization.

HPV vaccine can prevent HPV infection effectively. The college student’s vaccination status is unclear in mainland China. We assessed the knowledge, practice, and attitude towards HPV vaccine and compared the differences between medical and nonmedical students. It was a cross-sectional study using self-administered anonymous questionnaires. Nine-hundred sixty full-time college students were recruited randomly at Peking University in China. The medical students had higher level of knowledge of HPV and its vaccine than the nonmedical students (p