Untangling the environmental and tectonic drivers of the Noto earthquake swarm in Japan.

The underlying mechanism of the ongoing seismic swarm in the Noto Peninsula, Japan, which generates earthquakes at 10 times the average regional rate, remains elusive. We capture the evolution of the subsurface stress state by monitoring changes in seismic wave velocities over an 11-year period. A sustained long-term increase in seismic velocity that is seasonally modulated drops before the earthquake swarm. We use a three-dimensional hydromechanical model to quantify environmentally driven variations in excess pore pressure, revealing its crucial role in governing the seasonal modulation with a stress sensitivity of 6 × 10-9 per pascal. The decrease in seismic velocity aligns with vertical surface uplift, suggesting potential fluid migration from a high-pore pressure zone at depth. Stress changes induced by abnormally intense snow falls contribute to initiating the swarm through subsequent perturbations to crustal pore pressure.

Transcriptomic imputation of genetic risk variants uncovers novel whole-blood biomarkers of Parkinson's disease.

Blood-based gene expression signatures could potentially be used as biomarkers for PD. However, it is unclear whether genetically-regulated transcriptomic signatures can provide novel gene candidates for use as PD biomarkers. We leveraged on the Genotype-Tissue Expression (GTEx) database to impute whole-blood transcriptomic expression using summary statistics of three large-scale PD GWAS. A random forest classifier was used with the consensus whole-blood imputed gene signature (IGS) to discriminate between cases and controls. Outcome measures included Area under the Curve (AUC) of Receiver Operating Characteristic (ROC) Curve. We demonstrated that the IGS (n = 37 genes) is conserved across PD GWAS studies and brain tissues. IGS discriminated between cases and controls in an independent whole-blood RNA-sequencing study (1176 PD, 254 prodromal, and 860 healthy controls) with mean AUC and accuracy of 64.8% and 69.4% for PD cohort, and 78.8% and 74% for prodromal cohort. PATL2 was the top-performing imputed gene in both PD and prodromal PD cohorts, whose classifier performance varied with biological sex (higher performance for males and females in the PD and prodromal PD, respectively). Single-cell RNA-sequencing studies (scRNA-seq) of healthy humans and PD patients found PATL2 to be enriched in terminal effector CD8+ and cytotoxic CD4+ cells, whose proportions are both increased in PD patients. We demonstrated the utility of GWAS transcriptomic imputation in identifying novel whole-blood transcriptomic signatures which could be leveraged upon for PD biomarker derivation. We identified PATL2 as a potential biomarker in both clinical and prodromic PD.

Predicting influenza-like illness trends based on sentinel surveillance data in China from 2011 to 2019: A modelling and comparative study1.

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

RFG-TVIU: robust factor graph for tightly coupled vision/IMU/UWB integration.

High precision navigation and positioning technology, as a fundamental function, is gradually occupying an indispensable position in the various fields. However, a single sensor cannot meet the navigation requirements in different scenarios. This paper proposes a "plug and play" Vision/IMU/UWB multi-sensor tightly-coupled system based on factor graph. The difference from traditional UWB-based tightly-coupled models is that the Vision/IMU/UWB tightly-coupled model in this study uses UWB base station coordinates as parameters for real-time estimation without pre-calibrating UWB base stations. Aiming at the dynamic change of sensor availability in multi-sensor integrated navigation system and the serious problem of traditional factor graph in the weight distribution of observation information, this study proposes an adaptive robust factor graph model. Based on redundant measurement information, we propose a novel adaptive estimation model for UWB ranging covariance, which does not rely on prior information of the system and can adaptively estimate real-time covariance changes of UWB ranging. The algorithm proposed in this study was extensively tested in real-world scenarios, and the results show that the proposed system is superior to the most advanced combination method in all cases. Compared with the visual-inertial odometer based on the factor graph (FG-VIO), the RMSE is improved by 62.83 and 64.26% in scene 1 and 82.15, 70.32, and 75.29% in scene 2 (non-line-of-sight environment).

A LAMP-based hydrogen ion selective electrochemical sensor for highly sensitive detection of Mycoplasma pneumoniae.

A concise and rapid detection method for Mycoplasma pneumoniae is urgently required due to its severe impact on human health. To meet such a need, this study proposed and constructed an innovative point-of-care testing (POCT) platform that consists of a hydrogen ion-selective loop-mediated isothermal amplification (H+-LAMP) sensor and an electrochemical detection device. The H+-LAMP sensor successfully integrated the working and reference electrodes and converted the H+ generated during the LAMP process into an electrochemical signal. High sensitivity and stability for pathogen detection were also achieved by treating the working electrode with an electrodeposited polyaniline solid contact layer and by using an ion-selective membrane. As a result, the sensor shows a sensitivity of 68.26 mV per pH, a response time of less than 2 s, and a potential drift of less than 5 mV within one hour, which well meets the urgent need. The results also demonstrated that the detection limit for Mycoplasma pneumoniae was lowered to 1 copy per µL, the nucleic acid extraction and detection process could be completed in 30 minutes, and the impact of interfering ions on the sensor was negligible. Validation with 20 clinical samples yielded satisfactory results. More importantly, the storage lifespan of such an electrochemical sensor is over seven days, which is a great advantage for on-site pathogen detection. Therefore, the hydrogen ion-selective sensor constructed in this investigation is particularly suitable as a core component for instant pathogen detection platforms.

Enhanced quantum secret sharing protocol for anonymous secure communication utilizing W states.

Quantum secret sharing (QSS) represents the fusion of quantum mechanics principles with secret information sharing, allowing a sender to distribute a secret among receivers for collective recovery. This paper introduces the concept of quantum anonymous secret sharing (QASS) to enhance the practicality of such protocols. We propose a QASS protocol leveraging W states, ensuring both recover-security and anonymity of shared secrets. Our protocol undergoes rigorous evaluation verifying their accuracy and fortifying their security against scenarios involving the active adversary. Additionally, acknowledging the imperfections inherent in real-world communication channels, we conduct a comprehensive analysis of protocol security and efficacy in noisy quantum networks. Our investigations reveal that W states exhibit good performance in mitigating noise interference, making them apt for practical applications.

Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

DEMA: A Deep Learning-Enabled Model for Non-Invasive Human Vital Signs Monitoring Based on Optical Fiber Sensing.

Optical fiber sensors are extensively employed for their unique merits, such as small size, being lightweight, and having strong robustness to electronic interference. The above-mentioned sensors apply to more applications, especially the detection and monitoring of vital signs in medical or clinical. However, it is inconvenient for daily long-term human vital sign monitoring with conventional monitoring methods under the uncomfortable feelings generated since the skin and devices come into direct contact. This study introduces a non-invasive surveillance system that employs an optical fiber sensor and advanced deep-learning methodologies for precise vital sign readings. This system integrates a monitor based on the MZI (Mach-Zehnder interferometer) with LSTM networks, surpassing conventional approaches and providing potential uses in medical diagnostics. This could be potentially utilized in non-invasive health surveillance, evaluation, and intelligent health care.

Tuning cellular metabolism for cancer virotherapy.

Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity. However, hurdles like transient persistence and moderate efficacy necessitate innovative approaches. Metabolic remodeling has recently gained prominence as a strategic intervention, wherein OVs or combination regimens could reprogram tumor and immune cell metabolism to enhance viral replication and oncolysis. In this review, we summarize recent advances in strategic reprogramming of tumor and immune cell metabolism to enhance OV-based immunotherapies. Specific tactics include engineering viruses to target glycolytic, glutaminolytic, and nucleotide synthesis pathways in cancer cells, boosting viral replication and tumor cell death. Additionally, rewiring T cell and NK cell metabolism of lipids, amino acids, and carbohydrates shows promise to enhance antitumor effects. Further insights are discussed to pave the way for the clinical implementation of metabolically enhanced oncolytic platforms, including balancing metabolic modulation to limit antiviral responses while promoting viral persistence and tumor clearance.

Black soldier fly larvae bioconversion and subsequent composting promote larval frass quality during pig and chicken manure transformation process.

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.

Potential threats of microplastics and pathogenic bacteria to the immune system of the mussels Mytilus galloprovincialis.

As one of the main components of marine pollution, microplastics (MPs) inevitably enter the mussel aquaculture environment. At the same time, pathogenic bacteria, especially pathogens such as Vibrio, can cause illness outbreaks, leading to large-scale death of mussels. The potential harm of MPs and pathogenic bacteria to bivalve remains unclear. This study designed two experiments (1) mussels (Mytilus galloprovincialis) were exposed to 100 particles/L or 1,000 particles/L polymethyl methacrylate (PMMA, 17.01 ± 6.74 µm) MPs and 1 × 107 CFU/mL Vibrio parahaemolyticus at the same time (14 days), and (2) mussels were exposed to 100 particles/L or 1,000 particles/L MPs for a long time (30 days) and then exposed to 1 × 107 CFU/mL V. parahaemolyticus to explore the effects of these two stresses on the mussel immune system. The results showed that after the combined exposure of V. parahaemolyticus and MPs, the lysosomal membrane stability of hemocytes decreased, lysozyme activity was inhibited, and hemocytes were induced to produce more lectins and defensins to fight pathogenic invasion. Long-term exposure to MPs caused a large amount of energy consumption in mussels, inhibited most of the functions of humoral immunity, increased the risk of mussel infection with pathogenic bacteria, and negatively affected mussel condition factor, the number of hemocytes, and the number of byssuses. Mussels may allocate more energy to deal with MPs and pathogenic bacterial infections rather than for growth. Above all, MPs exposure can affect mussel immune function or reduce its stress resistance, which in turn has an impact on mollusk farming.

Me3SiBr-promoted cascade electrophilic thiocyanation/cyclization of ortho-alkynylanilines to synthesize indole derivatives.

A Lewis acid-promoted electrophilic thiocyanation/cyclization of ortho-alkynylanilines for the synthesis of indole derivatives has been developed. The reaction utilizes Me3SiBr as the Lewis acid and N-thiocyanatosuccinimide as the thiocyanation reagent. A series of 2-aryl-3-thiocyanato indoles were prepared in moderate to high yields under mild conditions without metals and oxidants. It provides an efficient protocol for the construction of the indole skeleton and C-SCN and C-N bonds in one step as well.

Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Discovery of indole-2-one derivatives as BRD4 (BD1) selective inhibitors.

Bromodomain protein 4 (BRD4) is a member of the BET family, and its overexpression is closely associated with the development of many tumors. Inhibition of BRD4 shows great therapeutic potential in anti-tumor, and pan-BRD4 inhibitors show adverse effects of dose limiting toxicity and thrombocytopenia in clinical trials. To improve clinical effects and reduce side effects, more efforts have focused on seeking selective inhibitors of BD1 or BD2. Herein, a series of indole-2-one derivatives were designed and synthesized through docking-guided optimization to find BRD4-BD1 selective inhibitors, and their BRD4 inhibitory and antiproliferation activities were evaluated. Among them, compound 21r had potent BRD4 inhibitory activity (the IC50 values of 41 nM and 313 nM in BD1 and BD2 domain), excellent anti-proliferation (the IC50 values of 4.64 ± 0.30 µM, 0.78 ± 0.03 µM, 5.57 ± 1.03 µM against HL-60, MV-4-11 and HT-29 cells), and displayed low toxicity against normal cell GES-1 cells. Further studies revealed that 21r inhibited proliferation by decreasing the expression of proto-oncogene c-Myc, blocking cell cycle in G0/G1 phase, and inducing apoptosis in MV-4-11 cells in a dose-dependent manner. All the results showed that compound 21r was a potent BRD4 inhibitor with BD1 selectivity, which had potential in treatment of leukemia.

Lysis-Free Isolation and Direct Amplification of Pathogenic Bacterial DNA Using Diatom Frustules.

DNA has been implicated as an important biomarker for the diagnosis of bacterial infections. Herein, we developed a streamlined methodology that uses diatom frustules (DFs) to liberate and capture bacterial DNA and allows direct downstream amplification tests without any lysis, washing, or elution steps. Unlike most conventional DNA isolation methods that rely on cell lysis to release bacterial DNA, DFs can trigger the oxidative stress response of bacterial cells to promote bacterial membrane vesicle formation and DNA release by generating reactive oxygen species in aqueous solutions. Due to the hierarchical porous structure, DFs provided high DNA capture efficiency exceeding 80% over a wide range of DNA amounts from 10 pg to 10 ng, making only 10 µg DFs sufficient for each test. Since laborious liquid handling steps are not required, the entire DNA sample preparation process using DFs can be completed within 3 min. The diagnostic use of this DF-based methodology was illustrated, which showed that the DNA of the pathogenic bacteria in serum samples was isolated by DFs and directly detected using polymerase chain reaction (PCR) at concentrations as low as 102 CFU/mL, outperforming the most used approaches based on solid-phase DNA extraction. Furthermore, most of the bacterial cells were still alive after DNA isolation using DFs, providing the possibility of recycling samples for storage and further diagnosis. The proposed DF-based methodology is anticipated to simplify bacterial infection diagnosis and be broadly applied to various medical diagnoses and biological research.

M1-type polarized macrophage contributes to brain damage through CXCR3.2/CXCL11 pathways after RGNNV infection in grouper.

The vertebrate central nervous system (CNS) is the most complex system of the body. The CNS, especially the brain, is generally regarded as immune-privileged. However, the specialized immune strategies in the brain and how immune cells, specifically macrophages in the brain, respond to virus invasion remain poorly understood. Therefore, this study aimed to examine the potential immune response of macrophages in the brain of orange-spotted groupers (Epinephelus coioides) following red-spotted grouper nervous necrosis virus (RGNNV) infection. We observed that RGNNV induced macrophages to produce an inflammatory response in the brain of orange-spotted grouper, and the macrophages exhibited M1-type polarization after RGNNV infection. In addition, we found RGNNV-induced macrophage M1 polarization via the CXCR3.2- CXCL11 pathway. Furthermore, we observed that RGNNV triggered M1 polarization in macrophages, resulting in substantial proinflammatory cytokine production and subsequent damage to brain tissue. These findings reveal a unique mechanism for brain macrophage polarization, emphasizing their role in contributing to nervous tissue damage following viral infection in the CNS.

A non-invasive method to determine core temperature for cats and dogs using surface temperatures based on machine learning.

BACKGROUND: Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. OBJECTIVES: Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. ANIMALS: 200 cats and 200 dogs treated between March 2022 and May 2022. METHODS: A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. RESULTS: The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. CONCLUSION: The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.

Feasibility and efficacy of endoscopy with blue laser imaging for the detection and diagnosis of cardia polyps: A single-center randomized controlled study.

OBJECTIVE: To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI). METHODS: Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed. RESULTS: The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns. CONCLUSION: BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.

Synthesis and proton-conductive behaviour of two MOFs with covalently bonded imidazoles in the channels.

Immobilization of imidazole molecules as proton carriers into MOFs to facilitate proton conduction is a general strategy for developing high proton conductive materials. Herein, we designed two imidazole substituted phthalic acid ligands and constructed two novel MOFs, {[Zr6(OH)16(H3L1)4]Cl8·20H2O}n [Zr-MOF; H3L1 = 2-(1H-imidazol-4-yl) methylaminoterephthalic acid] and {Gd(HCOO)(H2L2)2}n [Gd-MOF; H3L2 = 5-(1H-imidazol-4-yl)methylaminoisophthalic acid] and fully studied their porous nature, stability and water-assisted proton conduction. The resulting Zr-MOF exhibits a high proton conductivity of 1.82 × 10-2 S cm-1 at 98% RH and 80 °C, while Gd-MOF has a proton conductivity of 3.01 × 10-3 S cm-1 at 98% RH and 60 °C.

Development of real-time recombinase polymerase amplification (RPA) and RPA combined with lateral flow dipstick (LFD) assays for the rapid and sensitive detection of cyprinid herpesvirus 3.

In this issue, we established rapid, cost-effective, and simple detection methods including recombines polymerase amplification with lateral flow dipstick (RPA-LFD) and real-time RPA for cyprinid herpesvirus 3(CyHV-3), and evaluated their sensitivity, specificity, and applicability, the real-time RPA method could achieve sensitive diagnosis of CyHV-3 within 1.3 copies per reaction, respectively. The real-time RPA method is 10-fold more sensitive than RPA-LFD method. The exact number of CyHV-3 can be calculated in each sample by real-time RPA. The sera from koi also can be tested in these methods. In addition, no cross-reaction was observed with other related pathogens, including carp oedema virus (CEV), spring viraemia of carp virus (SVCV), cyprinid herpesvirus 1(CyHV-1), cyprinid herpesvirus 2(CyHV-2), type I grass carp reovirus (GCRV-I), type II GCRV (GCRV-II), type III GCRV (GCRV-III), and Aeromonas hydrophila.