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An ozone-based plasma pretreatment was proposed to reduce the oxygen vacancy and unstable germanium (Ge) suboxide (GeO $_{x}\text {)}$ at lower interface of interfacial layer (IL). With higher oxidizing ability of ozone and lower plasma damage in process, the formation of unstable GeOx at lower interface of IL can be effectively suppressed. The devices with a mixed hydrogen and ozone plasma (MHOP) pretreatment exhibit an ultrathin equivalent oxide thickness (EOT) of 0.57 nm, a fairly acceptable gate leakage current density of $3 \times 10^{-{3}}$ A/cm2, lower interface trap density of $10^{{11}}$ cm $^{-{2}}\cdot $ eV $^{-{1}}$ , and fewer border traps in Ge MOS capacitor. Also, a higher driver current of 1.4 mA, a lower subthreshold swing (SS) of 113 mV/dec, and higher on/off current ratio of $3.2 \times 10^{{3}}$ for Ge MOSFET can be achieved with an MHOP treatment.

I. INTRODUCTION: INSIDER TRADING IN A CONTROLLER-DOMINATED ENVIRONMENT 718 II. INSIDER TRADING LAW IN CHINA 719 A. Substantive Law 719 1. The Definition of Insider and Inside Information 720 2. [...], We conducted a comprehensive, up-to-date observation of the enforcement of insider trading law in China. Our observation has a twofold goal. First, we examine how a key component of modern securities law--insider trading law--is enforced in a rapidly growing economy where both regulators and market participants are relatively lacking in experience and must learn to communicate with one another and establish an effective model of law enforcement. Second, we use this observation as a lens for understanding how corporate information flows in a concentrated ownership environment. In theory, controlling shareholders can either voluntarily push for corporate information flow to the general public to win investor confidence, or they can trade for their own private benefit with an informational advantage and keep that information private as long as possible and bet that law enforcement does not detect it. Alternatively, company controllers may opt for a third option, which is to tacitly allow corporate managers to trade with undisclosed corporate information as a form of managerial compensation without conducting any insider trading themselves. Which scenario is more likely is unclear, but China's concentrated ownership environment makes it a good setting for testing these possibilities. We first discuss Chinese law against insider trading and then provide both quantitative and descriptive accounts of the law's enforcement. Quantitatively, we run an event study with a measure called pre-announcement degree of run-up as a proxy for overall insider trading in China. We then compare this result with a comparison group and data from other countries. We initially found a 65.8% pre-announcement stock price run-up in tried cases of insider trading in China, which is comparable to results in other countries with a dispersed corporate ownership structure. If insider trading in China occurs at a rate similar to that of other countries, then ownership structure would seem to play no significant role in it. However, after running our test again with a comparison group--a sample composed of 330 random major merger and acquisition events in China from 2007 to 2017--we discovered, contradictorily, that the degree of information leakage in the comparison group increased up to 83.9%. These disparate results highlight China's puzzling enforcement of insider trading law.

A HfO2/ZrO2/HfO2 (HZH) high-k stack with adequate ZrO2 thickness ratio is proposed as dielectric in metal-insulator–metal (MIM) capacitor for dynamic random access memory (DRAM) applications. The dielectric constant (k) of 43 is achieved when the ZrO2 thickness ratio is 73%. An equivalent oxide thickness (EOT) of 0.46 nm and leakage current density ( ${J} _{\text {g}}$ ) of $9.4\times 10^{-{5}}$ A/cm2 are simultaneously achieved with a total HZH physical thickness ( ${T} _{\text {ox}}$ ) of 5 nm. The leakage current may be caused by the interface traps at the HZH multi-interface structure, as well as the oxygen vacancies inside HfO2 and ZrO2. To suppress ${J} _{\text {g}}$ , a NH3 plasma treatment was in situ conducted during atomic layer deposition (ALD) processes of HZH deposition. Through nitrogen incorporation with in situ NH3 plasma treatment, the oxygen vacancies can be passivated, and Zr-O–N bonds would be formed at the interface to suppress the formation of interface traps. The sample with an in situ NH3 plasma treatment at the interface between ZrO2 and top HfO2 (ZN) can obtain a reduction in leakage current density by 48% when compared with those without ZN, while maintaining the capacitance density (C) at a similar value of around $7.4~\mu $ F/cm2. The approaches of HZH stack and in situ plasma treatment for MIM capacitor are promising to the cell in DRAM technology.

Background and Objectives: Smoothened (SMO), a key component of the hedgehog signaling pathway, represents a therapeutic target for triple negative breast cancer (TNBC), yet the chemotherapy response rate in TNBC patients is only 40–50%, underscoring the urgent need for the development of novel drugs to effectively treat this condition. The novel compound TPB15, an SMO inhibitor derived from [1,2,4] triazolo [4,3-α] pyridines, demonstrated superior anti-TNBC activity and lower toxicity compared to the first SMO inhibitor vismodegib in both in vitro and in vivo. However, the compound's pharmacokinetic properties remain unclear. The present work aims to develop a simple HPLC-MS/MS method to profile the pharmacokinetics and bioavailability of TPB15 in rats as a ground work for further clinical research. Methods: Separation was performed on an Agilent ZORBAX StableBond C18 column by gradient elution using acetonitrile and 0.1% formic acid as mobile phase at a flow rate of 0.3 mL/min. Multiple reaction monitoring(MRM) in positive mode with the transitions of m/z454.2 → 100.0, 248.1 → 121.1 was employed to determine TPB15 and internal standard tinidazole, respectively. The specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover of the method was validated. The pharmacokinetics and bioavailability  study of TPB15 were carried out on rats through intravenous injection at the dose of 5 mg/kg and oral gavage at the dose of 25 mg/kg, and the pharmacokinetics parameters were calculated by the non-compartment analysis using the pharmacokinetics software DAS 2.1.1. Results: The values of specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover satisfied the acceptable limits. The lower limit of quantification of this method was 10 ng/mL with a linear range of 10–2000 ng/mL. The validated method was then applied to pharmacokinetics and bioavailability studies in rat by dosing with gavage (25 mg/kg) and intravenous injection(5 mg/kg), and the oral bioavailability of TBP15 in rat was calculated as 16.4 ± 3.5%. The pharmacokinetic parameters were calculated as following: maximum of plasma concentration (Cmax) (PO: 2787.17 ± 279.45 µg/L), Time to maximum plasma concentration (Tmax) (PO: 4.20 ± 0.90 h), the area under the concentration-time curve 0 to time (AUC0–t) (PO: 17,373.03 ± 2585.18 ng/mL·h, IV: 21,129.79 ± 3360.84 ng/mL·h), the area under the concentration-time curve 0 to infinity (AUC0–∞) (PO: 17,443.85 ± 2597.63 ng/mL·h, IV: 17,443.85 ± 2597.63 ng/mL·h), terminal elimination half-life (t1/2) (PO: 7.26 ± 2.16 h, IV: 4.78 ± 1.09 h). Conclusions: TPB15, a promising candidate for treating TNBC, has demonstrated outstanding efficacy and safety in vitro and in vivo. This study established a simple, sensitive, and rapid HPLC-MS/MS bioanalytical method, developed and validated in accordance with FDA and EMA guidelines, for conducting pharmacokinetic and bioavailability studies of TPB15. The results revealed a favorable pharmacokinetic profile owing to its long t1/2. Nevertheless, the next phase of research should include formulation screening to enhance bioavailability, as well as clinical trials, metabolism pathway analysis, and assessment of potential drug-drug interactions.

The magmatic-hydrothermal transition in granite-related, rare-metal metallogenic systems has received great attention as economic rare metal (including rare earth) minerals reach saturation and trigger mineralization at this stage. However, deciphering the details of the melt-fluid evolution process and the distribution behavior of rare metals remains difficult. Here, we applied tourmaline chemistry and B isotopes to unravel processes at the magmatic-hydrothermal transition that are responsible for rare-metal partitioning in the Huoshibulake (HS) and Tamu (TM) REE-Nb-mineralized intrusions in Southern Tianshan, SW Central Asian Orogenic Belt. Three types of tourmaline are identified in the plutons: (1) disseminated tourmaline in the granite, with a brown-yellow core (HS-DB) and bluegreen rim (HS-DG); (2) orbicular tourmaline, with a brown-yellow core (HS-OB and TM-OB) and blue-green rim (HS-OG and TM-OG); and (3) vein tourmaline (HS-V and TM-V). Compositionally, all these tourmalines exhibit extremely low Ca and Mg contents and are classified as schorl. The substitution processes of major-element variations are dominantly caused by (Al,□)(Fe,Na)−1exchange vectors. Four generations of tourmaline crystallization are established based on the petrographic, compositional, and B isotopes evolution of the tourmaline. First, the HS-DB crystals crystallized from the highly evolved residual melt, and then HS-OB and TM-OB precipitated from immiscible B-rich aqueous melts during the magmatic-hydrothermal transition. Subsequently, the blue-green overgrowths (HS-DG, HS-OG, and TM-OG) crystallized from exsolved hydrothermal fluids. Finally, the formation of HS-V and TM-V resulted from another melt pulse from a deeper magma chamber. The magmatic tourmaline exhibits a narrow range of δ11B values between −12.6 to −10.0‰, while the hydrothermal tourmaline shows significantly heavier and variable δ11B values ranging from −10.2 to −4.9‰. The fractionation of B isotopes is reproduced by Rayleigh fractionation modeling. Lower Nb and Sn contents in the orbicular tourmaline relative to those precipitated from the residual melt, along with the lack of rare-metal minerals in the orbicules, indicate that B-rich melt/fluid exsolution does not necessarily contribute to the rare-metal mineralization. In comparison, the veins contain abundant rare-metal and REE minerals in close paragenesis with fluorite, and the vein tourmaline shows high- Nb and -Sn contents. These observations suggest that saturation of fluorite triggered the precipitation of rare metals, and fluorine played a critical role in rare metal concentration and mineralization. This study highlights the potential of tourmaline to trace the magmatic-hydrothermal transition and provide insights into rare-metal mineralization in the granitic systems.

AbstractThe pylon is one of the key force-bearing structures of a cable-bearing bridge. Combining the advantages of factory manufacturing and modular installation of steel pylons, and the higher rigidity and lower cost of reinforced concrete pylons, a steel shell–concrete composite pylon is proposed. In this article, the structural construction of a steel shell–concrete composite pylon is introduced in detail. The structural mechanical properties, action mechanism of the stiffened slab rib and both transverse and vertical tenon are probed. Also, design theories, principles and methods are established. The industrialized construction technology of steel shell–concrete composite pylons is studied. The test results show that the interface strain of the steel shell–concrete composite pylon satisfies the assumption of plane section. During the whole loading process, the steel shell and the concrete can work together to give full play to the role of steel and concrete. In practice, the construction of the Nanjing Jiangxinzhou Yangtze River Bridge has demonstrated that 80% of the construction workload of steel shell–concrete composite pylons can be factory completed, the construction speed can be increased significantly and the labor input for on-site construction operations can be reduced by 75%.

Crohn's disease (CD) is an inflammatory bowel disease whose pathogenesis remains unclear. In this paper, we reviewed the basic research of acupuncture and moxibustion in treating CD by regulating intestinal intrinsic immunity, and summarized in more detail that acupuncture and moxibustion can regulate the intestinal intrinsic immune system through the intestinal epithelial cell barrier, monocytes/macrophages, natural killer cells (NK cells), dendritic cells (DC), and neutrophils. Specifically, acupuncture and moxibustion can reduce the expression of inflammatory factors in the intestinal mucosa, alleviate intestinal fibrosis to repair the mechanical barrier of the intestinal mucosa, inhibit the expression of molecules of the MAPK, TLR/NF-κB signaling pathway and inflammatory factors, block the NK cell-mediated cytotoxicity pathway, and prevent the overactivation of neutrophils to control inflammatory responses, repairing the damaged intestinal tract and alleviating CD symptoms. This paper illustrated the characteristics of acupuncture and moxibustion for CD, which involves multi targets and pathways, aiming to provide guidance for the clinical application and basic research of acupuncture and moxibustion for CD. It also pointed out the current drawbacks of acupuncture and moxibustion therapy, and finally proposing the shortcomings of the current research, including the insufficient number of studies on acupuncture and moxibustion in the treatment of CD through the modulation of NK cells and neutrophils, the lack of standardization in acupuncture point selection, duration and treatment course, and the geographical limitations of the research locations for acupuncture and moxibustion in treating CD.

BackgroundThe association between the TDRD6variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6was found to be associated with oligoasthenoteratozoospermia (OAT).MethodsWhole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6-knockout mice were generated using the CRISPR–Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment.ResultsBi-allelic TDRD6variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6variants. ScRNA-seq analysis of germ cells from a patient with TDRD6variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation.ConclusionOur findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6variants, providing insights for potential clinical treatment strategies.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8and AK9were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

A necessary tuning rate estimation method to correct the positioning error caused by nonlinear effects in optical frequency-domain reflectometry (OFDR) systems is proposed. Unlike previous studies on nonlinear effects in OFDR systems, this article focuses on the adverse effects of nonlinear tuning on positioning accuracy, rather than on the spatial resolution of the system. Based on the nonlinear noise model of the tunable laser source (TLS), the mechanism of its effect on the positioning capability is discussed in this article, and the specific effects of each parameter in the noise model on the positioning accuracy are further investigated. In the proposed method, the common auxiliary reference signal is employed to estimate the phase information, and the correction of OFDR system positioning is achieved using the short-time Fourier transform (STFT) and the sine-fit algorithm. In this article, the effect of different kinds of nonlinear noise on the positioning capability of the system is discussed, and the possibility of using the proposed method to eliminate the positioning error is verified. Comparing the positioning capacity before and after correction, we can achieve a positioning accuracy enhancement of about 2.36% on a 310-m fiber under test (FUT).

The surface topography of the workpiece directly affects its service performance. In this study, CLSM and SEM are used to analyze the effects of turning speed, turning feed, and turning depth on the three dimensional topography and surface defects of the machined surface. Amplitude parameters are used to characterize the machined surface topography of hard turning. Twelve groups of single factor experiments are used to analyze the influence of turning parameters on surface topography. Based on analysis of variance (ANOVA) and 15 groups of Box-Behnken Design (BBD), whether cutting parameters have significant influence on arithmetic mean deviation (Sa) is analyzed. A mathematical statistical model of Sais established by Response Surface Methodology, and the effectiveness of the model is verified by 10 groups of experiments. By analyzing the research results, it can be concluded that: (1) The consistency of the surface topography of hard turning is good; (2) In the turning feed direction, the surface defects of the machined surface by hard turning include turning grooves, material side flow, adhering chips, and material surface tearing; (3) In hard turning, the most significant factor affecting the three dimensional roughness (Sa) is the turning feed.

Gerbera (Gerbera hybrida), a major fresh cut flower crop, is very susceptible to root rot disease. Although plant defensins (PDFs), a major group of plant antimicrobial peptides, display broad-spectrum antifungal and antibacterial activities, PDFgenes in gerbera have not been systematically characterized. Here, we identified and cloned nine PDFgenes from gerbera and divided them into two classes based on phylogenetic analysis. Most Class I GhPDFgenes were highly expressed in petioles, whereas all Class II GhPDFgenes were highly expressed in roots. Phytophthora cryptogeainoculation strongly upregulated all Class II GhPDFgenes in roots and upregulated all Class I GhPDFgenes in petioles. Transient overexpression of GhPDF1.5and GhPDF2.4inhibited P. cryptogeainfection in tobacco (Nicotiana benthamiana) leaves. Transient overexpression of GhPDF2.4, but not GhPDF1.5, significantly upregulated ACOand LOXgene expression in tobacco leaves, indicating that overexpressing GhPDF2.4activated the jasmonic acid/ethylene defense pathway and that the two types of GhPDFs have different modes of action. Prokaryotically expressed recombinant GhPDF2.4 inhibited mycelial growth and delayed the hyphal swelling of P. cryptogea, in vitro, indicating that GhPDF2.4 is a morphogenetic defensin. Moreover, the addition of GhPDF2.4 to plant culture medium alleviated the root rot symptoms of in vitro-grown gerbera seedlings and greatly reduced pathogen titer in P. cryptogea-inoculated gerbera roots in the early stages of treatment. Our study provides a basis for the use of GhPDFs, especially GhPDF2.4, for controlling root rot disease in gerbera.

Detecting leaks in water networks is a costly challenge. This article introduces a practical solution: the integration of optical network with water networks for efficient leak detection. Our approach uses a fiber-optic cable to measure vibrations, enabling accurate leak identification and localization by an intelligent algorithm. We also propose a method to access leak severity for prioritized repairs. Our solution detects even small leaks with flow rates as low as 0.027 L/s. It offers a cost-effective way to improve leak detection, enhance water management, and increase operational efficiency.

Distributed acoustic sensing (DAS) is an attractive technology that can turn existing fibre optic networks to real-time distributed vibration sensors. However, it encounters great challenges in handling the transmission, storage, and processing of voluminous data streams which are orders of magnitude larger than that collected from point sensors. The gap between intensive data generated by φ-OTDR and modern computing system with limited reading/writing speed and storage capacity leads to restrictions on many applications. Compressive sensing (CS) is a revolutionary signal acquisition method that allows a signal to be acquired and reconstructed with significantly fewer samples than that required by Nyquist-Shannon theorem. The data size is greatly reduced in the sampling stage, but the reconstruction of the compressed data is still time and computation consuming. To address this challenge, we propose to map the feature extractor from Nyquist-domain to compressed-domain and therefore vibration detection and classification can be directly implemented in compressed-domain. The measured results show that our method can be used to reduce the transmitted data size by 70% while achieves a true positive rate (TPR) of 99.4% and a false positive rate (FPR) of 0.04% of positioning along 5-km-long sensing fibre and a classification accuracy of 95.05% on a 5-class classification task.

The hexagonal cell topology of planar SiC VDMOSFETs with varied JFET width (LJFET) are designed and manufactured in this study. L ${_{\text {JFET}}} = 1.4\mu $ m has the best HF-FOM (R ${_{\text {on}}} \times $ Cgd) and HF-FOM (R ${_{\text {on}}} \times $ Qgd) by comparing the dynamic and static parameters of each design. Besides, the UIS reliability and failure mechanism for series designs are investigated by experiment and TCAD simulation. The results show that the high temperature is generated by energy dissipation during avalanche and it drives the parasitic BJT conduction, causing Ids out of control and instantaneous heat concentration in a very short time. The extremely high temperature causes internal cracking of the material and metal melting, resulting in gate-source short circuit and device damage. It would provide suggestions for device design and reliability consideration.

Conventional atmospheric microwave plasma sources face challenges in achieving plasma generation at the milliwatt power level, often requiring a reduction in operating pressure to generate plasma at lower power levels. This article presents a novel atmospheric microwave plasma source based on the coaxial structure to generate plasma at the milliwatt power level at atmospheric pressure. First, numerical simulations based on the finite element method (FEM) and equivalent transmission line model (ETLM) have been done to design the structure. Simulation results show that at the optimal structure, the microwave reflection ratio $\vert {S}_{{11}}\vert $ at 2.45 GHz is equal to −19.58 dB before plasma excitation and the electric field strength reaches $6.03\times 10^{{5}}$ V/m when the input power is 1 W. Second, a practical experimental system is built according to the simulations. Experimental results show that the $\vert {S}_{{11}}\vert $ at its resonant frequency is −19.2 dB before plasma excitation, which agrees well with the simulations. Moreover, the minimum input microwave power values for generating argon, CO2, and air plasmas are 100 mW, 5 W, and 10 W, respectively. Finally, this novel atmospheric microwave plasma source has been used to decompose and convert CO2, the highest conversion rate and energy efficiency reach 24.1% and 49.2%, respectively, which are comparable to low-pressure microwave plasmas. Thus, the proposed microwave plasma source in this article has great potentials for industrial applications to reduce carbon emissions.

Molecular dynamics simulation has become a major theoretical analysis method for ultra precision machining of various materials. Large Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) is used to construct a molecular dynamics model for cutting polycrystalline Fe-Cr-W alloy with CBN tool. The geometric parameters of the tool model are: the rake angle is −10°, the clearance angle is 7°, and the tool tip radius is 1.5 nm, including 8570 atoms. The size of the workpiece model is 24 nm × 10 nm × 10 nm, including 203,893 atoms. Ovito is used to visually analyze the influence of cutting parameters on the machinability of workpieces. The results show that the extrusion of the tool on the workpiece makes the atoms of the workpiece move and become chips and machined surfaces. Excessive cutting speed and depth will produce large hydrostatic stress, large cutting force, high cutting temperature and deteriorate the machined surface.

Food allergy is a multifactorial interplay process influenced not only by the structure and function of the allergen itself but also by other components of the food matrix. For food, before it is thoroughly digested and absorbed, numerous factors make the food matrix constantly change. This will also lead to changes in the chemistry, biochemical composition, and structure of the various components in the matrix, resulting in multifaceted effects on food allergies. In this review, we reveal the relationship between the food matrix and food allergies and outline the immune role of the components in the food matrix, while highlighting the ways and pathways in which the components in the food matrix interact and their impact on food allergies. The in-depth study of the food matrix will essentially explore the mechanism of food allergies and bring about new ideas and breakthroughs for the prevention and treatment of food allergies.

Colorectal cancer (CRC) is a global health challenge with high morbidity and mortality. Radiomics, an emerging field, utilizes quantitative imaging features extracted from medical images for CRC diagnosis, staging, treatment response assessment, and prognostication. This review highlights the potential of radiomics for personalized CRC management. Radiomics enables noninvasive tumor characterization, aiding in early detection and accurate diagnosis, and it can be used to predict tumor stage, lymph node involvement, and prognosis. Furthermore, radiomics guides personalized therapies by assessing the treatment response and identifying patients who could benefit. Challenges include standardizing imaging protocols and analysis techniques. Robust validation frameworks and user‐friendly software are needed for the integration of radiomics into clinical practice. Despite challenges, radiomics offers valuable insights into tumor biology, treatment response, and prognosis in CRC. Overcoming technical and clinical hurdles will unlock its full potential in CRC management. This review covers the role of radiomics in CRC diagnosis, staging, treatment response assessment, and prediction of treatment outcomes, and also discusses the challenges associated with implementing radiomics in clinical practice and highlighted the need for standardization and validation in this field. Furthermore, the review explores future directions, such as the integration of artificial intelligence and machine learning algorithms, which can further enhance the capabilities of radiomics in CRC.

ABSTRACTOsteosarcoma and osteochondroma are the most common malignant and benign bone tumours. In order to distinguish osteosarcoma from osteochondroma, divide-specific areas and distinguish different lesions. Herein, a computer-aided medical diagnosis was developed for the first time based on existing mask regional convolutional neural network (Mask R-CNN) to detect them in X-ray radiographs used for their initial screening. Mask R-CNN was trained using an amplified training and validation sets consisting of 378 and 52 ×-ray radiographs and propose the removing heterogeneous module and the de-overlapping module in the post-processing process to obtain the predictive segmentation mask. Two tests were used to predict, which were composed of 84 images from 72 patients involved in the training set but different from the images used within, and 61 images from 35 new patients who were not included in the training set. The mean Average Precision, mean Precision, mean Recall and mean Intersection Over Union were introduced metrics to evaluate the performance, which were 0.9486, 0.9211, 0.9545 and 0.6603 for test sets 1, and 0.9290, 0.8690, 0.9481 and 0.6222 for test 2. The results demonstrated that the developed method was convincing in distinguishing the type and detecting the region of osteosarcoma and osteochondroma compared with manual work.

We propose and experimentally demonstrate an enhanced quasi-distributed accelerometer array based on phase-sensitive optical time-domain reflectometry ( $\phi $ -OTDR) and ultraweak fiber Bragg grating (UWFBG). By utilizing a transducer cylinder, the vibration can be easily converted to an axial strain of the sensing fiber, which enables a high sensitivity in vibration measurement. Furthermore, a UWFBG array that contains backscattering enhanced points along the fiber is employed to improve the signal-to-noise ratio (SNR). Consequently, quasi-distributed vibration sensing with a resolution of 0.03 g and a flat sensitivity of 1.4 rad/g in a frequency range from 50 to 800 Hz is realized over 500-m long UWFBG. The proposed sensing system offers high-sensing sensitivity, large multiplexing capacity, and anti-interference fading, which can be applied for structural health monitoring of large buildings and machinery.

In order to study the influence of tool geometry on the machining mechanism of alloy tool steel in the process of ultra precision turning, the polycrystalline molecular dynamics model of alloy tool steel is established with Fe, Cr and W, and the molecular dynamics model of tool is established with B and N. Four potential energy functions, Tersoff, EAM, Morse and L-J, are used to characterize the interaction between atoms in the model. The effects of tool geometry on hydrostatic stress, cutting force, cutting temperature and amorphous atoms in the turning process are analyzed. Research indicates:(1) Hydrostatic stress is mainly concentrated in the contact position between the tool tip and the workpiece, and it is compressive stress; (2) Cutting forces fluctuate and are significantly affected by tool geometry; (3) The cutting heat of about 1000K is concentrated in the chip, and the tool clearance angle has a great influence on the cutting temperature. (4) Amorphous atoms are formed at the chip location and the machined surface, and eventually turn into chips and the metamorphic layer of the machined surface.

In this paper, the penalty unsymmetric finite element framework for the consistent couple stress theory is derived from the virtual work principle. The C 1 continuity requirement is satisfied in weak form by using the penalty function method to constrain the independently introduced rotations for approximating the mechanical rotations, enabling the utilization of C ° continuous interpolations for designing the element displacement without the loss of convergence property. Within the proposed framework, 8-node quadrilateral element and 20-node hexahedral solid element are constructed for analyzing the size-dependent mechanical responses of consistent couple stress elasticity materials. In these developments, the quadratic serendipity isoparametric shape functions are enriched by the rotation degrees of freedom for determining the test functions, whilst the metric stress functions that are derived from the concerned equilibrium equations are used to design the trial functions. A series of numerical benchmarks are examined for verifying their effectiveness and accuracy. It is shown that the elements can efficiently capture the size dependences, exhibiting good accuracy and low susceptibility to mesh distortion. [ABSTRACT FROM AUTHOR]

The recognition of supersonic inlet flow pattern has become a research hotspot in recent years. In this paper, the dual external pressure supersonic inlet is taken as the research object. To explore the flow characteristics of the inlet, time-mean processing on the inlet pressure signal collected by sensors is conducted first, and the features of the inlet pressure data in time domain and frequency domain are extracted, respectively. As feature selection (FS) plays an important role in classification tasks and has been recently studied as a multi-objective optimization problem, two objectives of FS are considered and an improved non-dominated sorting genetic algorithm NSGA2 with hybrid mutation operators using support vector machines (SVM) as classifiers is proposed, aiming to simultaneously select feature subsets and optimize SVMs hyper-parameters. In addition, a way to deal with variation transgression is proposed to make the mutation operator of the single-objective evolution fit well in the multi-objective evolution algorithm. Experimental results on 31 sensor datasets demonstrate that our proposed algorithm can achieve competitive classification accuracy while obtaining a smaller size of feature subset compared with particle swarm optimization algorithm and some multi-objective optimization algorithms using single-objective evolution mutation operators.

Background: Bi-allelic variants in DNAH11have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. Methods: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11variants. Results: In this study, we identified seven novel variants in the DNAH11gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11gene variants.

Due to the complexity of e-learning mode, the behaviour characteristics of online autonomous learning are different, and the existing research methods cannot comprehensively study the behaviour characteristics. Therefore, this paper puts forward the research on the behaviour characteristics of distance online autonomous learning in different network virtual environments. This paper uses data mining technology to mine the data of online autonomous learning behaviour characteristics, analyses the general characteristics of different types of students' learning behaviour, summarises the influencing factors and characteristic dimensions of online autonomous learning mode, and analyses the influence of learners' personality characteristics on distance online autonomous learning. Through the questionnaire survey experiment, the reliability coefficient of this method in analysing the differences of autonomous learning behaviour characteristics is calculated. The reliability coefficient of this study is above 0.786, which can better grasp online learning resources and improve students' online autonomous learning ability.

BackgroundSpermatogenic impairments can lead to male infertility by different pathological conditions, such as multiple morphological abnormalities of the sperm flagella (MMAF) and non-obstructive azoospermia (NOA). Genetic factors are involved in impaired spermatogenesis.Methods and resultsHere, we performed genetic analyses through whole-exome sequencing in a cohort of 334 Han Chinese probands with severe MMAF or NOA. Biallelic variants of CFAP54were identified in three unrelated men, including one homozygous frameshift variant (c.3317del, p.Phe1106Serfs*19) and two compound heterozygous variants (c.878G>A, p.Arg293His; c.955C>T, p.Arg319Cys and c.4885C>T, p.Arg1629Cys; c.937G>A, p.Gly313Arg). All of the identified variants were absent or extremely rare in the public human genome databases and predicted to be damaging by bioinformatic tools. The men harbouring CFAP54mutations exhibited abnormal sperm morphology, reduced sperm concentration and motility in ejaculated semen. Significant axoneme disorganisation and other ultrastructure abnormities were also detected inside the sperm cells from men harbouring CFAP54mutations. Furthermore, immunofluorescence assays showed remarkably reduced staining of four flagellar assembly-associated proteins (IFT20, IFT52, IFT122 and SPEF2) in the spermatozoa of CFAP54-deficient men. Notably, favourable clinical pregnancy outcomes were achieved with sperm from men carrying CFAP54mutations after intracytoplasmic sperm injection treatment.ConclusionOur genetic analyses and experimental observations revealed that biallelic deleterious mutations of CFAP54can induce severe MMAF and NOA in humans.

Background: Intensive care unit (ICU) resources are inadequate for the large population in China, so it is essential for physicians to evaluate the condition of patients at admission. In this study, our objective was to construct a machine-learning risk prediction model for mortality in respiratory intensive care units (RICUs). Methods: This study involved 817 patients who made 1,063 visits and who were admitted to the RICU from 2012 to 2017. Potential predictors such as demographic information, laboratory results, vital signs and clinical characteristics were considered. We constructed eXtreme Gradient Boosting (XGBoost) models and compared performances with random forest models, logistic regression models and clinical scores such as Acute Physiology and Chronic Health Evaluation II (APACHE II) and the sequential organ failure assessment (SOFA) system. The model was externally validated using data from Medical Information Mart for Intensive Care (MIMIC-III) database. A web-based calculator was developed for practical use. Results: Among the 1,063 visits, the RICU mortality rate was 13.5%. The XGBoost model achieved the best performance with the area under the receiver operating characteristics curve (AUROC) of 0.860 (95% confidence interval (CI): 0.808 - 0.909) in the test set, which was significantly greater than APACHE II (0.749, 95% CI: 0.674 - 0.820; P = 0.015) and SOFA (0.751, 95% CI: 0.669 - 0.818; P = 0.018). The Hosmer-Lemeshow test indicated a good calibration of our predictive model in the test set with a P-value of 0.176. In the external validation dataset, the AUROC of XGBoost model was 0.779 (95% CI: 0.714 - 0.813). The final model contained variables that were previously known to be associated with mortality, but it also included some features absent from the clinical scores. The mean N-terminal pro-B-type natriuretic peptide (NTproBNP) of survivors was significantly lower than that of the non-survival group (2066.43 pg/mL vs. 8232.81 pg/mL; P < 0.001). Conclusions: Our results showed that the XGBoost model could be a suitable model for predicting RICU mortality with easy-to-collect variables at admission and help intensivists improve clinical decision-making for RICU patients. We found that higher NT-proBNP can be a good indicator of poor prognosis.

To investigate the unclamped inductive switch (UIS) characteristics, 1200 V silicon carbide (SiC) planar MOSFETs with four cell topologies of linear, current sharing linear, square, and hexagon are designed and manufactured. The experimental platform was built and tested. The results show that the single pulse avalanche energy density of the linear cell topology is 1.69 times higher than that of the square and 1.49 times that of the hexagon. Further, the UIS process is simulated by using physical simulation, which shows that the avalanche energy was concentrated near the corner of the P-base region in the UIS mode. From this, the avalanche energy distribution differences of the four cell topologies were analyzed and compared. A theoretical model of avalanche heating per unit area is proposed, which shows that the avalanche energy density is inversely proportional to the proportion of avalanche energy concentration region. This study may contribute to the cell topology design of SiC MOSFETs under the application scenario with high avalanche reliability requirements.

BackgroundAs a common type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) can cause male infertility. Previous studies have revealed genetic factors as a major cause of MMAF. The known MMAF-associated genes are involved in the mitochondrial sheath, outer dense fibre or axoneme of the sperm flagella. These findings indicate the genetic heterogeneity of MMAF.Methods and resultsHere, we conducted genetic analyses using whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of AKAP3(A-kinase anchoring protein 3) were identified in two MMAF-affected men from unrelated families. One AKAP3variant was a frameshift (c.2286_2287del, p.His762Glnfs*22) and the other variant was a missense mutation (c.44G>A, p.Cys15Tyr), which was predicted to be damaging by multiple bioinformatics tools. Further western blotting and immunofluorescence assays revealed the absence of AKAP3 in the spermatozoa from the man harbouring the homozygous frameshift variant, whereas the expression of AKAP3 was markedly reduced in the spermatozoa of the man with the AKAP3missense variant p.Cys15Tyr. Notably, the clinical outcomes after intracytoplasmic sperm injection (ICSI) were divergent between these two cases, suggesting a possibility of AKAP3 dosage-dependent prognosis of ICSI treatment.ConclusionsOur study revealed AKAP3as a novel gene involved in human asthenoteratozoospermia.

Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P= 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P= 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P= 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P= 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.

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Due to the abundance of bioactive components, surficial decoration with cell-derived extracellular matrix (ECM) is a promising strategy to improve the biological functionality of the tissue engineering scaffolds. However, decellularization is necessary to remove antigenic components in the ECM that may trigger adverse immune response. Freeze–thaw (FT) cycles and treatment with Triton X-100/ammonium hydroxide (TN) are two commonly used decellularization methods for ECM, but their effects on both growth factor retention and antigen removal are still controversial. The objectives of this study are to compare the preservation of ECM texture and beneficial ingredients and the removal of cellular antigens by these two methods. First, the constructs combined bone marrow mesenchymal stem cell-derived ECM and poly(lactic-co-glycolic acid) (PLGA) membrane are prepared and decellularized using FT and TN treatments. Moreover, the effects of decellularization on the ultrastructure and the composition of ECM-decorated PLGA membrane are compared by scanning electron microscope observation and protein quantification. Furthermore, the ECM deposited on PLGA is stripped off and then implanted subcutaneously in rats, and the host macrophage and local lymphocyte responses were investigated. Finally, ECM-decorated porous PLGA scaffolds are implanted into rat calvarial defects, and the new bone formation is evaluated. Our results showed that both methods effectively removed DNA. TN treatment partially retained collagen, glycosaminoglycan, bone morphogenetic protein-2, and vascular endothelial growth factor, and better preserved structural integrity than FT treatment. ECM implants decellularized by both methods induced a mild host response after subcutaneous implantation. Although the total content of residual DNA in the two ECMs digested by the DNA enzyme seemed to be similar and very low, the interfaces between implanted materials and natural tissues in the TN group recruited lower numbers of CD68+macrophages, CD68+CD86+(M1) macrophages, and CD4+T lymphocytes than that in FT group, implying that there exist other ECM antigens to influence immune response besides DNA. Furthermore, ECM-decorated scaffolds decellularized by TN treatment induced greater bone formation than that of bare scaffolds in vivo, demonstrating the effective retention of ECM bioactive components after decellularization. This study showed that TN treatment was a more effective and safer decellularization method than FT cycles.Impact statementDecellularization is a prerequisite for extracellular matrix (ECM) application, but there is still no standard for its selection. This study demonstrated that detergent treatment was more effective than freeze–thaw (FT) cycles in removing ECM antigens besides DNA, and the prepared ECM elicited a milder allogenic immune response, which ensured the safety of ECM. Moreover, detergent better preserved the ECM integrity than FT cycles, and effectively retained growth factors, and the decellularized ECM-decorated scaffolds significantly promoted bone repair, which ensured the effectiveness of ECM. This study provides the theoretical and experimental bases for the decellularization strategy of ECM-modified tissue engineering scaffolds.

Inlet flow pattern recognition is one of the most crucial issues and also the foundation of protection control for supersonic air-breathing propulsion systems. This article proposes a hybrid algorithm of fast K-nearest neighbors (F-KNN) and improved directed acyclic graph support vector machine (I-DAGSVM) to solve this issue based on a large amount of experimental data. The basic idea behind the proposed algorithm is combining F-KNN and I-DAGSVM together to reduce the classification error and computational cost when dealing with big data. The proposed algorithm first finds a small set of nearest samples from the training set quickly by F-KNN and then trains a local I-DAGSVM classifier based on these nearest samples. Compared with standard KNN which needs to compare each test sample with the entire training set, F-KNN uses an efficient index-based strategy to quickly find nearest samples, but there also exists misclassification when the number of nearest samples belonging to different classes is the same. To cope with this, I-DAGSVM is adopted, and its tree structure is improved by a measure of class separability to overcome the sequential randomization in classifier generation and to reduce the classification error. In addition, the proposed algorithm compensates for the expensive computational cost of I-DAGSVM because it only needs to train a local classifier based on a small number of samples found by F-KNN instead of all training samples. With all these strategies, the proposed algorithm combines the advantages of both F-KNN and I-DAGSVM and can be applied to the issue of large-scale supersonic inlet flow pattern recognition. The experimental results demonstrate the effectiveness of the proposed algorithm in terms of classification accuracy and test time.

High pressure represents extreme environments and provides opportunities for materials discovery1–8. Thermal transport under high hydrostatic pressure has been investigated for more than 100 years and all measurements of crystals so far have indicated a monotonically increasing lattice thermal conductivity. Here we report in situ thermal transport measurements in the newly discovered semiconductor crystal boron arsenide, and observe an anomalous pressure dependence of the thermal conductivity. We use ultrafast optics, Raman spectroscopy and inelastic X-ray scattering measurements to examine the phonon bandstructure evolution of the optical and acoustic branches, as well as thermal conductivity under varied temperatures and pressures up to 32 gigapascals. Using atomistic theory, we attribute the anomalous high-pressure behaviour to competitive heat conduction channels from interactive high-order anharmonicity physics inherent to the unique phonon bandstructure. Our study verifies ab initio theory calculations and we show that the phonon dynamics—resulting from competing three-phonon and four-phonon scattering processes—are beyond those expected from classical models and seen in common materials. This work uses high-pressure spectroscopy combined with atomistic theory as a powerful approach to probe complex phonon physics and provide fundamental insights for understanding microscopic energy transport in materials of extreme properties.

In recent years, the development of deep learning technology has made breakthroughs in computer vision, natural language processing and other fields. The Smart Water Grid (SWG) technology based on deep learning has also been a hot area of research in recent years. It has achieved better performance in the related detection and prediction of urban pipe networks. Therefore, this survey paper presents an extensive review of the application of deep learning to several different issues related to the SWG. This paper emphasises feasibility studies and summarises the state-of-the-art development in this field from a technical point of view, which consists of pipeline leakage and burst detection, contamination source identification and water demand forecasting. Furthermore, this paper also proposes challenges and future directions in these key research areas, demonstrating that deep learning-based SWG technology is still an emerging and encouraging research field.

Asthenozoospermia (AZS) is a common male infertility phenotype, accounting for 18% of infertile patients. The N-DRC (Nexin-dynein Regulatory Complex) complex is the motor regulating device in the flagellum, which is found in most eukaryotic organisms with flagellum. The deletion of TCTE1 (T-Complex-Associated Testis-Expressed 1), a component of the N-DRC complex also known as DRC5 (Dynein regulatory complex subunit 5), has been shown to cause asthenospermia in mice. This study mainly introduces a clinical case of male infertility with normal sperm count, normal morphological structure, but low motility and weak forward movement. By whole-exome sequencing, we found that TCTE1became a frameshift mutant, ENST00000371505.5: c.396_397insTC (p.Arg133Serfs*33), resulting in the rapid degradation of TCTE1 protein and male infertility. This phenotype is similar to the Tcte1−/−(Tcte1knockout) mice, which showed structural integrity but reduced motility. Further, different from mice, in vitro Fertilization (IVF) could successfully solve the patient’s problem of infertility. Our data provides a better understanding of the biological functions of TCTE1 in human flagellum assembly and male fertility.

ABSTRACTCartilage and joint damage easily degenerates cartilage and turns into osteoarthritis (OA), which seriously affects human life and work, and has no cure currently. The temporal and spatial changes of multiple microenvironments upon the damage of cartilage and joint are noticed, including the emergences of inflammation, bone remodeling, blood vessels, and nerves, as well as alterations of extracellular and pericellular matrix, oxygen tension, biomechanics, underneath articular cartilage tissues, and pH value. This review summarizes the existing literatures on microenvironmental changes, mechanisms, and their negative effects on cartilage regeneration following cartilage and joint damage. We conclude that time-dependently rebuilding the multiple normal microenvironments of damaged cartilage is the key for cartilage regeneration after systematic studies for the timing and correlations of various microenvironment changes.

Pneumocystispneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality.

Objective: To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome (IBS) visceral hyperalgesia model rats and its regulatory effect on P2X3 receptors in the spinal cord, anterior cingutate cortex (ACC) and thalamic ventral posterolateral nucleus (VPL). Methods: Thirty 8-day-old newborn rats were randomly divided into a normal group (n=6) and a modeling group (n=24) according to the completely random number table method. Rats in the normal group were bred routinely, and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention (CRD) in stimulation method. Rats successfully modelled were re-divided into a model group, a mild moxibustion group, a P2X3 receptor antagonist group, and a normal saline group according to the completely random number table method with 6 rats in each group. Rats in each group received corresponding interventions from the 37-day old, once a day for 7 consecutive days. Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord, ACC and VPL of rats. Results: Under different intensities of CRD stimulation, the abdominal withdrawal reflex (AWR) scores of the model group were significantly increased versus the normal group (all P&lt;0.05); the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P&lt;0.01). The P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the model group were significantly increased versus the normal group (all P&lt;0.01); the P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P&lt;0.01). Conclusion: Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord, ACC, and VPL tissues of IBS visceral hyperalgesia model rats, which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.

The superconducting magnet system of a fusion reactor plays a vital role in plasma confinement, a process that can be disrupted by various operational factors. A critical parameter for evaluating the temperature margin of superconducting magnets during normal operation is the nuclear heating caused by D–T neutrons. This study investigates the impact of nuclear heating on a superconducting magnet system by employing an improved analysis method that combines neutronics and thermal hydraulics. In the magnet system, toroidal field (TF) magnets are positioned closest to the plasma and bear the highest nuclear-heat load, making them prime candidates for evaluating the influence of nuclear heating on stability. To enhance the modeling accuracy and facilitate design modifications, a parametric TF model that incorporates heterogeneity is established to expedite the optimization design process and enhance the accuracy of the computations. A comparative analysis with a homogeneous TF model reveals that the heterogeneous model improves accuracy by over 12%. Considering factors such as heat load, magnetic-field strength, and cooling conditions, the cooling circuit facing the most severe conditions is selected to calculate the temperature of the superconductor. This selection streamlines the workload associated with thermal-hydraulic analysis. This approach enables a more efficient and precise evaluation of the temperature margin of TF magnets. Moreover, it offers insights that can guide the optimization of both the structure and cooling strategy of superconducting magnet systems.

•Edaravone protects hippocampal neurons by eliminating H2O2or glutamate-induced toxicity.•Edaravone restores the levels of BDNF, FGF2, and their related signaling axes to attenuate apoptotic cell death.•Edaravone is an effective drug for neuronal protection.

Recent Scanning Tunneling Spectra(STS) measurements on underdoped cuprates have found that the maximum superconducting transition temperature Tcincreases when the size of charge transfer gap (CTG) is reduced. Applying pressure is another well-known method to increase the maximum Tc. However, these pressure experiments also found that Tcis enhanced in underdoped and optimally-doped samples but suppressed in overdoped ones. Here we present a possible mechanism based on the charge fluctuation to explain both these observed effects. Starting from the 3-band Hubbard model, we retrieve the charge fluctuation (CF) between the oxygen 2p6band and copper 3d10band, which is ignored in the t−Jmodel. This model is investigated using the variational Monte Carlo method(VMC).

Iodoacetic acid (IAA) is the most genotoxic iodinated disinfection byproduct known in drinking water. Previous studies have shown that IAA may be an endocrine disruptor. However, whether IAA has reproductive and developmental toxicity remains unclear. In this study, the reproductive and developmental toxicity of IAA was evaluated using a battery of in vitroand in vivoreproductive/developmental toxicity screening tests. The results of E-Screen, uterotrophic, and H295R steroidogenesis assays were negative. The Hershberger bioassay revealed that IAA could induce significant increases in absolute and relative weights of paired Cowper’s glands. Moreover, there was an increasing trend in the relative weights of the ventral prostate. The micromass test showed that IAA could inhibit the differentiation of midbrain and limb bud cells. A reproductive/developmental toxicity screening test showed that IAA resulted in significantly increased relative weights of testis and seminal vesicles plus coagulating glands in parental male rats, with a dose–response relationship. IAA could not only induce head congestion in offspring but also decrease litter weight, viability index, and anogenital distance index of male pups on postnatal day 4. All these results indicated that IAA had reproductive and developmental toxicity.

Although DNA 5-hydroxymethylcytosine (5hmC)is recognized as an important epigenetic mark in cancer, its precise role in lymph node metastasisremains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive primary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkersto predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.