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The saturated metasandstone is taken as the research object, and the uniaxial compression characteristics of the saturated metasandstone are simulated by means of the artificially made saturated sandstone samples. By checking the parameters of the Particle Flow Code (PFC) numerical simulation of loading and unloading seepage stress coupling, the effects of the conductivity coefficient, the pipe diameter, the apparent volume of the domain and the time step on the calculation results are analyzed. When PFC is used for numerical simulation of seepage stress coupling, the conductivity coefficient K can be taken as 0.010. When the pipe diameter is 1.0 mm, the apparent volume of the current domain is 1 x 10–6 m3, the water pressure distribution inside the sample is relatively uniform. The influence of time step on the compressive strength and peak strain of the specimen can be almost ignored. Under the action of water pressure, the compressive strength of the intact rock like sample and the rock like sample with cracks decreases, and the compressive strength of the sample decreases gradually with the increase of water pressure. When the inclined angle of fracture is the same, the seepage pressure is the same, and the confining pressure is the same, the compressive strength of the specimen also increases with the increase of the initial axial stress level during unloading. When the confining pressure and the osmotic pressure are the same, the unloading effect makes the crack development of the specimen faster and more complete, the specimen is more fragmented and multiple parallel shear bands develop.

The Rainfall thresholds are among the most commonly used criteria for predicting rainfall-induced landslides. However, existing empirical rainfall thresholds mainly focused on regional landslide warnings, lacking consideration for the spatial variability of rainfall thresholds for individual landslides within the region. This study uses historical rainfall-induced landslide data and hourly rainfall data from Bazhong City (2014 – 2021) to employ Kriging interpolation methods. It extracts four types of short-term rainfall (1 hour, 12 hours, 24 hours, 72 hours) and their corresponding long-term rainfall (7 days before the landslide occurrence). In these four threshold models, the distribution of long-term and short-term rainfall thresholds in each group is calculated and then validated using landslide disaster data from 2021. The research results indicate that the prediction accuracy of the four threshold models ranges from 40% to 65%, suggesting good potential for practical application. Additionally, the prediction accuracy improves with the increase in the duration of short-term rainfall. The prediction accuracy for rainfall thresholds calculated from the 72-hour-7-day model is highest, reaching 62%, while the 1-hour-7-day model achieves 46%. Based on the highest prediction accuracy of these models, the study calculates the optimal ratios for short-term and long-term disaster-causing rainfall for four types of models. This leads to a quantitative division between short-term rainfall-induced landslides and long-term rainfall-induced landslides. By calculating the spatial distribution of disaster-causing rainfall, the study extracts rainfall thresholds at potential landslide locations, achieving the goal of one threshold per site in the region and enhancing existing models for calculating rainfall thresholds.

Take the metamorphic sandstone as the reference object, by making rock like samples with fractures, the conventional triaxial loading and unloading test and PFC numerical simulation of rock like sample with single fracture were conducted, and the effects of the loading path, inclined angle of fracture, axial stress level during unloading, initial confining pressure during unloading on the compressive strength, peak strain and crack propagation evolution of the samples were considered. The compressive strength of the specimen under triaxial unloading is smaller than that under triaxial loading. The peak strain of the specimen under triaxial unloading is also smaller than that under triaxial loading. The specimen is more prone to brittle failure. When the axial stress level is the same during unloading, with the increase of the initial confining pressure during unloading, the difference of the compressive strength of the specimens with different inclined angles of fracture gradually decreases. Under the condition of uniaxial compression and triaxial compression, the failure of all specimens is tensile failure, and the shear failure is the main one during unloading.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 ( MET ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, MET ex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1–56.3%], the DCR was 81.3% (95% CI: 63.6–92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6–9.7) and 17.0 month (95% CI: 10.3–not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) μg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

Abstract Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

In this study, the uniaxial compression test and PFC 2D numerical simulation were carried out on the artificial rock specimen with T-shaped prefabricated fractures. The effects of the lengths l1, l2 of the main fractures, the length l3 of the secondary fracture, and the angle β between the secondary fracture and the loading direction on the uniaxial compressive strength and crack evolution law of specimen were studied. The research results show that the change of l1, l2 and β has obvious effect on the compressive strength and crack growth of the specimen, but the change of l3 has little effect on the compressive strength of the specimen. When l3 = 40 mm and l1 ≠ l2, the angle β influences on the crack propagation and failure mode of the specimen.

The surface water and groundwater in the mountainous area are vulnerable to contamination from the mining and transportation construction in Sichuan Province, China. Pollutants produced by anthropogenic activities transport within the groundwater from mountains to rivers on the plain, transferring contamination to the surface water. This study investigates the process of groundwater flow and contaminant transport from mountains to the lowlands based on synthetic numerical models. Two key factors are considered: precipitation and the slope of the mountain. Based on the real situation in Sichuan Province, four rainfall recharge rates are defined as 600, 800, 1,000, and 1,200 mm/yr, and five slope angles are considered: 20°, 25°, 30°, 35°, and 40°. The simulation results reveal that the groundwater level and solute transport are strongly influenced by the precipitation amounts and slope angles. The mountains with lower slopes maintain a relatively higher groundwater level under steady-state rainfall conditions; for example, groundwater levels decrease from 340 m to 300 m as slope angles increase at a 1,200 mm/yr precipitation level. Contaminant transport from the source in the mountain to the surface river is faster with increasing precipitations and decreasing slope angles. The model with 20° slope angle and 1,200 mm/yr precipitation exhibits the fastest solute migration, with the contaminant arrival time of 65 years. Furthermore, the models with 35° and 40° slope angles at a 600 mm/yr precipitation level show the slow transport speed with the contaminant arrival time of more than 75 years. In addition, higher precipitation may lead to more contaminant transport to the river. The analysis and findings of this study offer valuable insights into groundwater protection at the boundaries of mountains and plains.

Abstract With the advancement of micro/nanotechnologies, multielectrodes arrays (MEAs) with different three‐dimensional (3D) micro/nanostructures have been developed to achieve intracellular action potential recording of cardiomyocytes. However, the effect of the 3D micro/nanostructures density on the intracellular recording has not been fully investigated. In this work, 3D tunable nanodensity electrode arrays (TNDEA) are fabricated by hydrothermal synthesis and standard microfabrication to explore the effect of nanodensity regulation on intracellular biosensing. By low‐voltage electroporation, the signal quality of intracellular potentials recorded by the low‐nanodensity TNDEA showed was significantly improved compared to those recorded by the high‐nanodensity TNDEA. The low‐nanodensity TNDEA improved the amplitude (up to 7.7 mV), signal‐to‐noise ratio (SNR) (up to 69.46 dB), recording duration (up to 83 min), and recording yield (∼100%). The 3D nanodensity regulating strategy has achieved sensitive and prolonged intracellular biosensing of action potentials and is expected to be a powerful electrophysiological research tool in the biomedical field.

Dynamic biaxial compression tests and Particle Flow Code numerical simulations of the cement mortar specimens with a single joint were carried out to study the mechanical properties and crack evolution of artificial rock samples with a single joint. The effects of lateral stress 𝜎2, loading rate V , the dip angle β (between the vertical loading direction and the joint) on the biaxial compressive strength 𝜎 b, and the evolution lawof crackwere investigated. Test results showed that; (1) when both the dip angle β and the loading rate V remained unchanged, the biaxial compressive strength 𝜎 b increased with the increase in the lateral stress 𝜎2, while 𝜎2 had no obvious effect on the crack evolution law; (2) when both the dip angle β and the lateral stress 𝜎2 were kept unchanged, the loading rate V had an insignificant effect on the biaxial compressive strength 𝜎 b and the crack evolution law; (3) when both the lateral stress 𝜎2 and the loading rate V were constant, the biaxial compressive strength 𝜎 b decreased first and then increased with the increase in the dip angle β ; however, the dip angle β did not significantly affect the crack evolution law. The conclusions obtained in this paper are presented for the first time.

IntroductionCoastal karst aquifers face the risk of seawater intrusion due to groundwater development. Based on the conceptualization of Woodville Karst Plain (WKP), this study investigates the effect of karst conduit and pumping conditions on the aquifer vulnerability and pumping security.MethodsAccording to the purposes of this study, two cases are considered: one with conduit and one without. Salinization levels are compared between two cases, considering pumping rates ranging from 50 to 200 m3/day and various pumping locations throughout the on-shore region.ResultsThe results reveal that the aquifer with conduit is more susceptible to seawater intrusion at low pumping rates, whereas both scenarios experience significant salinization at high pumping rates. Specifically, in the non-conduit case, contamination is most prevalent when wells are located in the middle of the aquifer, while in the conduit case, pumping from inland areas poses high vulnerability. Moreover, conduit case and non-conduit case display different regions for pumping clean water. At low pumping rates, both cases show saline water being pumped from wells near the shore, and clean water is obtained from inland wells. At high pumping rates, the non-conduit case allows for clean water extraction from wells situated further inland, while in the conduit case, no wells within the entire aquifer are deemed safe.DiscussionThe analysis and findings of this study offer valuable insights for the management of groundwater in coastal karst aquifers, encompassing vulnerability assessment, selection of pumping locations, and determination of pumping rates.

In this study, direct shear tests were carried out on cement mortar specimens with singleladder, single-rectangular, and double-rectangular step joints. Consequently, the shear strength, and crack shape of specimens with these through-step joints were analyzed, for understanding the influence of the through-step joint’s shape on the direct shear mechanical properties. The results of the investigation are as follows: (1) Under the same normal stress, any increases in the height ℎ of the step joint causes an initial-increase-decrease in the shear strengths of specimens with single-ladder and double-rectangular step joints, causing a type-Wvariation pattern for the specimens with single-rectangular step joint. More essentially, when normal stress and ℎ are constant, the shear strength of specimens with a single-ladder step joint is the greatest, followed by specimens with a double-rectangular step joint, and then specimens with a single-rectangular step joint is the least. (2) Furthermore, given a smallℎ and low normal stress, specimen with a single-ladder step joint mainly experiences shear failure, whereas specimens with single-rectangular and double-rectangular step joints mainly generate extrusion milling in the step joints.

Abstract Genetic testing plays an important role in human health management and disease prevention. However, traditional genetic testing methods have been unable to fulfill the current diagnostic needs owing to several limitations, including high cost, complexity, and difficulty in performing. Smartphones have multiple inherent advantages, such as easy portability, ubiquity, fast processing speed, and excellent imaging capabilities, and have enormous potential in realizing rapid on‐site genetic testing. The present review documents the research progress of smartphone‐based optical imaging biosensors in the fields of colorimetry, fluorescence, and microscopic imaging for genetic testing. Furthermore, the review describes their potential applications in diagnostics, which range from infectious diseases to hereditary diseases and cancers. Finally, the challenges and perspectives of smartphone‐based optical imaging biosensors regarding genetic testing are discussed.

Abstract Electrophysiological recording is a widely used method to investigate cardiovascular pathology, pharmacology and developmental biology. Microelectrode arrays record the electrical potential of cells in a minimally invasive and high-throughput way. However, commonly used microelectrode arrays primarily employ planar microelectrodes and cannot work in applications that require a recording of the intracellular action potential of a single cell. In this study, we proposed a novel measuring method that is able to record the intracellular action potential of a single cardiomyocyte by using a nanowell patterned microelectrode array (NWMEA). The NWMEA consists of five nanoscale wells at the center of each circular planar microelectrode. Biphasic pulse electroporation was applied to the NWMEA to penetrate the cardiomyocyte membrane, and the intracellular action potential was continuously recorded. The intracellular potential recording of cardiomyocytes by the NWMEA measured a potential signal with a higher quality (213.76 ± 25.85%), reduced noise root-mean-square (~33%), and higher signal-to-noise ratio (254.36 ± 12.61%) when compared to those of the extracellular recording. Compared to previously reported nanopillar microelectrodes, the NWMEA could ensure single cell electroporation and acquire high-quality action potential of cardiomyocytes with reduced fabrication processes. This NWMEA-based biosensing system is a promising tool to record the intracellular action potential of a single cell to broaden the usage of microelectrode arrays in electrophysiological investigation.

Abstract Cardiovascular disease is the number one cause of death in humans. Therefore, cardiotoxicity is one of the most important adverse effects assessed by arrhythmia recognition in drug development. Recently, cell-based techniques developed for arrhythmia recognition primarily employ linear methods such as time-domain analysis that detect and compare individual waveforms and thus fall short in some applications that require automated and efficient arrhythmia recognition from large datasets. We carried out the first report to develop a biosensing system that integrated impedance measurement and multiparameter nonlinear dynamic algorithm (MNDA) analysis for drug-induced arrhythmia recognition and classification. The biosensing system cultured cardiomyocytes as physiologically relevant models, used interdigitated electrodes to detect the mechanical beating of the cardiomyocytes, and employed MNDA analysis to recognize drug-induced arrhythmia from the cardiomyocyte beating recording. The best performing MNDA parameter, approximate entropy, enabled the system to recognize the appearance of sertindole- and norepinephrine-induced arrhythmia in the recording. The MNDA reconstruction in phase space enabled the system to classify the different arrhythmias and quantify the severity of arrhythmia. This new biosensing system utilizing MNDA provides a promising and alternative method for drug-induced arrhythmia recognition and classification in cardiological and pharmaceutical applications.

In this study, the uniaxial compression test and the numerical simulation of the twodimensional particle flow code (PFC2D) were used to study the mechanical properties and failure laws of rock masses with parallel cracks. The experiment considers the influences of crack length (��º, crack angle (��1, ��2), and numerical changes in the rock bridge length (ℎ) and bridge angle (��) on failures of rock-like specimens. The results indicate that the uniaxial compressive strength (UCS) of the rock-like specimens with parallel cracks decreases with increasing �� under different �� values. The smaller angle between the preset crack and the loadinging direction (��) resulting in higher UCS. In addition, a larger ℎ results in higher UCS in the specimen. When ��1 or ��2 is fixed, the UCS and elastic modulus of the specimen show an ‘M’ shape with an increase in ��. Moreover, the crack growth or failure mode of samples with different �� values is similar. When ��1 or ��2 is small, the failure of the specimen is affected by the development and expansion of wing cracks. If one of ��1 and ��2 is large, the failure of the specimen is dominated by the expansion and development of the secondary cracks which is generated at the tip of the prefabricated crack. Furthermore, when the angle between the prefabricated crack and the loading direction is ��1 = 0°, the rock bridge is less likely to reach penetration failure as ℎ increases. Secondary crack connections between the prefabricated cracks occur only when �� is small. When �� ¡ 30°, the failure mode of the specimen is crack tip cracking which leads to penetration failure of the specimen, or the overall splitting failure.

The tunnel lining segments are assumed to be rigid, and the tensile, compression, shear, and bending properties of the joints are considered. A simplified calculation method for the dynamic response of the structure under the ground shock is proposed, and its correctness is verified by comparing it with results from the finite element method. Using this method, the dynamic response of a subway tunnel lining is calculated, the change in joint force is studied, and the influence of the angle between the load and the center of the minimum segment and the wavelength–diameter ratio on the peak joint force is examined. The results indicate that under the ground shock, shallow tunnel lining is in the impulsive regime, and the force of segment joints is mainly compressed. As the wavelength–diameter ratio increases, the peak values of the lining top displacement and vertical deformation increase significantly, and the proportion of displacement and deformation caused by the inertial force gradually decreases. Sine and cosine functions can be used to preliminarily judge if the bending moment and radial force of the joint are too large or too small, so that the resistance of the lining to ground shock can be improved to a certain extent by setting the positions of lining joints reasonably.

Hepatocellular carcinoma is one of the malignancies worldwide with a high mortality rate and an increasing incidence. Molecular Targeted agents are its common first-line treatment. Organoid technology, as a cutting-edge technology, is gradually being applied in the development of therapeutic oncology. Organoid models can be used to perform sensitivity screening of targeted drugs to facilitate the development of innovative therapeutic agents for the treatment of hepatocellular carcinoma. The purpose of this review is to provide an overview of the opportunities and challenges of hepatocellular carcinoma organoids in targeted drug sensitivity testing as well as a future outlook.

In this study, we tried to understand the horizontal bearing performances of step-tapered piles using numerical simulations. The influence of the geometric parameters, e.g. the diameter ( D) and the distance (L), and the length ( H) of the pile were considered, and the soil distribution imposed on the horizontal bearing capacity of the piles was simulated. Numerical results show that when the other geometrical parameters of step-tapered piles are kept unchanged: (a) the increasing diameter ( D) of the enlarged upper part of step-tapered piles improves the horizontal ultimate bearing capacity of step-tapered piles; (b) reduced distance ( L) improves the horizontal ultimate bearing capacity of the step-tapered piles; (c) Increasing length ( H) of the enlarged upper part of steptapered piles increases the horizontal ultimate bearing capacity; (d) the reduced length ( H) decreases the bending moment of the pile body. Higher soil strength surrounding the enlarged upper part of step-tapered piles can increase the horizontal ultimate bearing capacity of step-tapered piles. The change of soil strengths at the end of the step-tapered piles does not influence the horizontal ultimate bearing capacity of step-tapered piles.

Heavy metal contamination in soil has become a serious environmental problem in China, and chromium is one of the major threats to human health. In order to better understand the transfer pattern of heavy metal hexavalent chromium from polluted sites into surface water, the influencing factors that affect solute transfer from soil into the surface runoff with linear and nonlinear adsorption equations based on a two-layer incomplete mixing model were analyzed in this study. The Quasi-Newton method was used to optimize model parameters by fitting with the experimental laboratory data of chromium (Cr(VI)) in surface runoff. The local sensitivity analysis and the Morris global sensitivity analysis approaches were used to assess the parameter importance of rainfall intensity p, the thickness of the mixing layer hmix, incomplete mixing parameter α and γ, the soil adsorption parameters, and the initial soil water content θ0. The study results showed that the optimized nonlinear models were better consistent with the experimental results than the linear adsorption equation model. The results of global sensitivity indicated that rainfall intensity p was the main factor influencing Cr(VI) transport from the soil into surface runoff. The hmix and the α in the two-layer model were vital parameters that influenced such transport processes. Moreover, the soil adsorption properties and the θ0 had the lowest effects on runoff Cr(VI) loss. The results indicate that for controlling pollution migration in surface runoff, it is essential to focus on the analysis of precipitation conditions and soil properties that control the thickness of the mixing layer and the degree of mixing.

The study of brain science is vital to human health. The application of hyperspectral imaging in biomedical fields has grown dramatically in recent years due to their unique optical imaging method and multidimensional information acquisition. Hyperspectral imaging technology can acquire two-dimensional spatial information and one-dimensional spectral information of biological samples simultaneously, covering the ultraviolet, visible and infrared spectral ranges with high spectral resolution, which can provide diagnostic information about the physiological, morphological and biochemical components of tissues and organs. This technology also presents finer spectral features for brain imaging studies, and further provides more auxiliary information for cerebral disease research. This paper reviews the recent advance of hyperspectral imaging in cerebral diagnosis. Firstly, the experimental setup, image acquisition and pre-processing, and analysis methods of hyperspectral technology were introduced. Secondly, the latest research progress and applications of hyperspectral imaging in brain tissue metabolism, hemodynamics, and brain cancer diagnosis in recent years were summarized briefly. Finally, the limitations of the application of hyperspectral imaging in cerebral disease diagnosis field were analyzed, and the future development direction was proposed.

Hypocalcemia is a disease that adversely affects the production and reproduction of dairy cows. A portable device for rapid bovine blood calcium sensing has been growing in demand. Herein, we report a smartphone-based ratiometric fluorescence probe (SRFP) platform as a new way to detect and quantify calcium ions (Ca2+) in blood serum. Specifically, we employed a cost-effective and portable smartphone-based platform coupled with customized software that evaluates the response of Ca2+ ions to ratiometric fluorescence probe in bovine serum. The platform consists of a three-dimensional (3D) printed housing and low-cost optical components that excite fluorescent probe and selectively transmit fluorescence emissions to smartphones. The customized software is equipped with a calibration model to quantify the acquired fluorescence images and quantify the concentration of Ca2+ ions. The ratio of the green channel to the red channel bears a highly reproducible relationship with Ca2+ ions concentration from 10 μM to 40 μM in bovine serum. Our detection system has a limit of detection (LOD) of 1.8 μM in bovine serum samples and the recoveries of real samples ranged from 92.8% to 110.1%, with relative standard deviation (RSD) ranging from 1.72% to 4.89%. The low-cost SRFP platform has the potential to enable campesino to rapidly detect Ca2+ ions content in bovine serum on-demand in any environmental setting.

Abstract Light manipulation has drawn great attention in photodetectors towards the specific applications with broadband or spectra-selective enhancement in photo-responsivity or conversion efficiency. In this work, a broadband light regulation was realized in photodetectors with the improved spectra-selective photo-responsivity by the optimally fabricated dielectric microcavity arrays (MCAs) on the top of devices. Both experimental and theoretical results reveal that the light absorption enhancement in the cavities is responsible for the improved sensitivity in the detectors, which originated from the light confinement of the whispering-gallery-mode (WGM) resonances and the subsequent photon coupling into active layer through the leaky modes of resonances. In addition, the absorption enhancements in specific wavelength regions were controllably accomplished by manipulating the resonance properties through varying the effective optical length of the cavities. Consequently, a responsivity enhancement up to 25% within the commonly used optical communication and sensing region (800 to 980 nm) was achieved in the MCA-decorated silicon positive-intrinsic-negative (PIN) devices compared with the control ones. This work well demonstrated that the leaky modes of WGM resonant dielectric cavity arrays can effectively improve the light trapping and thus responsivity in broadband or selective spectra for photodetection and will enable future exploration of their applications in other photoelectric conversion devices.

Recognition of different kinds of human intrusions from the environmental disturbance with high efficiency is still a challenging task in perimeter security monitoring with fiber optic vibration sensor, since the vibration signals induced by these events are highly similar to each other, and it can not be directly discriminated by the signals. In this paper, an intelligent event recognition scheme is proposed to improve its performance in complicated environmental applications. In this event recognition scheme, a variational mode decomposition based kurtosis feature combined with a zero crossing rate feature is used as the input feature vectors. A support vector machine is used to classify the input feature vectors into the corresponding categories. A series of field tests show that the proposed scheme can accurately and rapidly classify wind disturbance and three typical patterns of human intrusions such as waggling the fence, climbing the fence and knocking the fence. The average identification rate of 100.0% and 96.9% are achieved for the wind disturbance and human intrusion events, respectively. The recognition processing time can be controlled less than 0.4 s. Thus, the intelligent event recognition scheme can fully satisfy the online monitoring requirements for practical applications.

In this paper, a high efficiency multiple events recognition scheme based on a hybrid feature extraction algorithm and a combined classifier for distributed optical fiber vibration sensing (DOFVS) system has been proposed and demonstrated. The hybrid feature vectors are extracted by using zero crossing rate, sample entropy, wavelet packet energy entropy, kurtosis, and multiscale permutation entropy. A combined classifier of support vector machine and radial basis function neural network is proposed to improve the reliability of the recognition results. The recognition result is given only when both of the two classifiers output same event types. The experimental results demonstrated that the average identification rate of five typical patterns (no intrusion, waggling the fence, climbing the fence, kicking the fence, and cutting the fence) over 97% is achieved through the combined classifier. Moreover, the whole recognition processing speed of the combined scheme is also good of real time performance, which can be limited in 1.1 s. Therefore, this kind of events recognition scheme has a quite promising application prospects in DOFVS system.

A high-throughput instrument to measure the full spectral properties of biochemical agents is necessary for fast screening in fields such as medical tests, environmental monitoring, and food analysis. However, this need has currently not been fully met by the commercial microplate reader (CMR). In this study, we have developed an automated high-throughput efficient microplate reader (AHTEMR) platform by combining a spectrometer and high-precision ball screw two-dimensional motion slide together, for high-throughput and full-spectrum-required biochemical assays. A two-dimensional slide working on a ball screw was driven by a stepper motor with a custom-designed master control circuit and used as a motion system of the AHTEMR platform to achieve precise positioning and fast movement of the microplate during measurements. A compact spectrometer was coupled with an in-house designed optical pathway system and used to achieve rapid capture of the full spectral properties of biochemical agents. In a performance test, the AHTEMR platform successfully measured the full spectral absorbance of bovine serum albumin (BSA) and glucose solution in multiple wells of the microplate within several minutes and presented the real-time full spectral absorbance of BSA and glucose solution. Compared with the CMR, the AHTEMR is 79 times faster in full-spectrum measurements and 2.38 times more sensitive at the optimal wavelength of 562 nm. The rapid measurement also demonstrated the great capacity of the AHTEMR platform for screening out the best colorimetric wavelengths for tests of BSA and glucose development, which will provide a promising approach to achieving high-throughput and full-spectrum-required biochemical assays.

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

Chemodynamic therapy (CDT) based on intracellular Fenton reactions is attracting increasing interest in cancer treatment. A simple and novel method to regulate the tumor microenvironment for improved CDT with satisfactory effectiveness is urgently needed. Therefore, glutathione (GSH)/ROS (reactive oxygen species) dual-responsive supramolecular nanoparticles (GOx@BNPs) for chemo–chemodynamic combination therapy were constructed via host–guest complexation between water-soluble pillar[6]arene and the ferrocene-modified natural anticancer product betulinic acid (BA) prodrug, followed by encapsulation of glucose oxidase (GOx) in the nanoparticles. The novel supramolecular nanoparticles could be activated by the overexpressed GSH and ROS in the tumor microenvironment (TME), not only accelerating the dissociation of nanoparticles—and, thus, improving the BA recovery and release capability in tumors—but also showing the high-efficiency conversion of glucose into hydroxyl radicals (·OH) in succession through intracellular Fenton reactions. Investigation of antitumor activity and mechanisms revealed that the dramatic suppression of cancer cell growth induced by GOx@BNPs was derived from the elevation of ROS, decrease in ATP and mitochondrial transmembrane potential (MTP) and, finally, cell apoptosis. This work presents a novel method for the regulation of the tumor microenvironment for improved CDT, and the preparation of novel GSH/ROS dual-responsive supramolecular nanoparticles, which could exert significant cytotoxicity against cancer cells through the synergistic interaction of chemodynamic therapy, starvation therapy, and chemotherapy (CDT/ST/CT).

Ordovician-Silurian subduction, Early Devonian arc-contient collision and followed post-collision extension are recorded in the north of the North China Craton. Most previous research has focused on the first two processes. Discussion on the post-collisional extension and its tetonic regime is still limited. In this study, 40Ar-39Ar muscovite ages obtained from the central part of the northern North China Craton were analyzed to shed light on the timing of post-collision extension. Garnet muscovite schist and muscovite quartz schist in the Jianshan Formation yielded 40Ar-39Ar muscovite plateau ages of 412 ± 3 Ma and 391 ± 3 Ma, respectively. Two other 40Ar-39Ar muscovite plateau ages (389 ± 2 Ma and 397 ± 2Ma) were obtained for two Mesoproterozoic monzogranites intruding into the Jianshan Formation. Based on previous research, the northern North China Craton underwent a collision event with Bainaimiao arc at c. 415 Ma, followed by post-collision extension in early Late Paleozoic. Therefore, combined with the newly acquired muscovite 40Ar-39Ar dating results, the Jianshan Formation might go through regional metamorphism at c. 412 Ma during the collision process. Subsequently, the Jianshan Formation and monzogranites intruding into it went through rapid exhumation along with metamorphism at c. 397–389 Ma in a post-collision extensional setting. The muscovite 40Ar-39Ar ages provide new markers for the exhumation history and the post-collisional extension setting during Early-Late Devonian in the study area. Furthermore, slab breakoff as the cause for this extensional setting is argued by the emplacement of the Early-Late Devonian alkaline rocks.

A universal method combining the differential quadrature finite element method with the virtual spring technique for analyzing the free vibration of thin plate with irregular cracks is proposed. Translational and rotational springs are introduced to restrain the vertical displacement and orientation of the plate. The mass matrix and stiffness matrix for each element are deduced involving the effects of the virtual springs. The connection relationships between elements can be modified by setting the stiffness of the virtual springs. The vibration of two rectangular plates with three irregular shaped cracks and different boundary conditions are presented. The results are compared with those obtained by ANSYS, where the good agreement between the results validates the accuracy and efficiency of the present method.