ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

CGMega: explainable graph neural network framework with attention mechanisms for cancer gene module dissection.

Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

Gstp1 negatively regulates blood pressure in hypertensive rat via promoting APLNR ubiquitination degradation mediated by Nedd4.

Hypertension is a leading risk factor for disease burden worldwide. Vascular contraction and remodeling contribute to the development of hypertension. Glutathione S-transferase P1 (Gstp1) plays several critical roles in both normal and neoplastic cells. In this study, we investigated the effect of Gstp1 on hypertension as well as on vascular smooth muscle cell (VSMC) contraction and phenotypic switching. We identified the higher level of Gstp1 in arteries and VSMCs from hypertensive rats compared with normotensive rats for the first time. We then developed Adeno-associated virus 9 (AAV9) mediated Gstp1 down-regulation and overexpression in rats and measured rat blood pressure by using the tail-cuff and the carotid catheter method. We found that the blood pressure of spontaneously hypertensive rats (SHR) rose significantly with Gstp1 down-regulation and reduced apparently after Gstp1 overexpression. Similar results were obtained from the observations of 2-kidney-1-clip renovascular (2K1C) hypertensive rats. Gstp1 did not influence blood pressure of normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Further in vitro study indicated that Gstp1 knockdown in SHR-VSMCs promoted cell proliferation, migration, dedifferentiation and contraction, while Gstp1 overexpression showed opposite effects. Results from bioinformatic analysis showed that the Apelin/APLNR system was involved in the effect of Gstp1 on SHR-VSMCs. The rise in blood pressure of SHR induced by Gstp1 knockdown could be reversed by APLNR antagonist F13A. We further found that Gstp1 enhanced the association between APLNR and Nedd4 E3 ubiquitin ligases to induce APLNR ubiquitination degradation. Thus, in the present study, we discovered a novel anti-hypertensive role of Gstp1 in hypertensive rats and provided the experimental basis for designing an effective anti-hypertensive therapeutic strategy.

Heat stroke: Pathogenesis, diagnosis, and current treatment.

Recently, the incidence of heat-related illnesses has exhibited a steadily upward trend, which is closely associated with several environmental factors such as climate change and air pollution. The progression of heat-related illnesses is a continuous process and can progress to the terminal period when it transforms into heat stroke, the most severe form. Heat stroke is markedly by a core body temperature above 40°C and central nervous system dysfunction. Current knowledge suggests that the pathogenesis of heat stroke is complex and varied, including inflammatory response, oxidative stress, cell death, and coagulation dysfunction. This review consolidated recent research progress on the pathophysiology and pathogenesis of heat stroke, with a focus on the related molecular mechanisms. In addition, we reviewed common strategies and sorted out the drugs in various preclinical stages for heat stroke, aiming to offer a comprehensive research roadmap for more in-depth researches into the mechanisms of heat stroke and the reduction in the mortality of heat stroke in the future.

Acute kidney injury following chimeric antigen receptor T-cell therapy: Epidemiology, mechanism and prognosis.

Chimeric antigen receptor T cell (CAR-T) therapy is a promising treatment for hematologic tumors, and adverse events of acute kidney injury (AKI) have been reported. However, its incidence, clinical characteristics, and prognosis remained unclear. We searched PubMed, EMBASE, and Web of Science for study about AKI after CAR-T therapy, a total of 15 studies, comprising 694 patients, were included. Among the 694 patients, 154 (22%) developed AKI, of which 89 (57.8%) were in stage 1, 59 (38.3%) were in stage 2 or 3, and 6 (3.9%) were not reported. Cytokine release syndrome is considered to be the most common cause of AKI. Of the 154 AKI patients, only 16 (10.4%) received renal replacement therapy, most AKI recovered renal function after symptomatic treatment. Although the occurrence of AKI after CAR-T therapy is rare and mostly mild, active knowledge of its pathogenesis, timely diagnosis and treatment are necessary for clinicians.

Activation and Autoinhibition Mechanisms of NLR Immune Receptor Pi36 in Rice.

Nucleotide-binding and leucine-rich repeat receptors (NLRs) are the most important and largest class of immune receptors in plants. The Pi36 gene encodes a canonical CC-NBS-LRR protein that confers resistance to rice blast fungal infections. Here, we show that the CC domain of Pi36 plays a role in cell death induction. Furthermore, self-association is required for the CC domain-mediated cell death, and the self-association ability is correlated with the cell death level. In addition, the NB-ARC domain may suppress the activity of the CC domain through intramolecular interaction. The mutations D440G next to the RNBS-D motif and D503V in the MHD motif autoactivated Pi36, but the mutation K212 in the P-loop motif inhibited this autoactivation, indicating that nucleotide binding of the NB-ARC domain is essential for Pi36 activation. We also found that the LRR domain is required for D503V- and D440G-mediated Pi36 autoactivation. Interestingly, several mutations in the CC domain compromised the CC domain-mediated cell death without affecting the D440G- or D503V-mediated Pi36 autoactivation. The autoactivate Pi36 variants exhibited stronger self-associations than the inactive variants. Taken together, we speculated that the CC domain of Pi36 executes cell death activities, whereas the NB-ARC domain suppressed CC-mediated cell death via intermolecular interaction. The NB-ARC domain releases its suppression of the CC domain and strengthens the self-association of Pi36 to support the CC domain, possibly through nucleotide exchange.

Ozaki technique versus ross operation for complex aortic valve diseases in children: A retrospective cohort study.

BACKGROUND: The Ozaki technique demonstrated promising results in adults, but few studies reported on pediatric patients with limited follow-up time. This study aimed to evaluate the mid-term results of Ozaki technique compared with Ross operation for complex aortic valve (AV) diseases in children. MATERIALS AND METHODS: One hundred and seventeen children underwent either Ozaki (n = 64) or Ross (n = 53) operation from January 2017 to December 2023. The primary endpoint was incidence of moderate or severe regurgitation/stenosis (AR/AS) post procedure. RESULTS: No significant difference was observed in age (6.5±3.4 vs. 7.9±4.3 years) and weight (25.9±15.5 vs. 31.0±25.9 kgs) at surgery. The Ozaki group had significantly more patients in heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and more patients needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. The Ozaki group were in worse status with more patients occurred heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. During follow up (20.4±17.3 vs. 22.7±22.8 months, P = 0.526), five patients (7.8%) in Ozaki group but no patients in Ross group required reoperations. The incidence of moderate or severe AR (28.1% vs. 3.1%) and AS (31.3% vs. 5.7%) were significantly higher than Ross group. Multivariate analysis identified lower age [HR:1.282 (95%CI:1.075-1.529), P = 0.006] and ECMO installation [HR:0.126 (0.018-0.887), P = 0.037] to be risk factors for moderate or severe AR, and higher aortic transvalvular gradient before discharge was confirmed as the only risk factor for moderate or severe AS (≥36 mmHg) at follow up in Ozaki group. CONCLUSION: Ozaki technique may be used as a palliative procedure for complex AV diseases in children, but its' mid-term results were not durable as Ross surgery, especially younger patients.

Kinetic Monte Carlo simulations on electroforming in nanomanipulated conductive bridge random access memory devices.

Conductive bridge random access memory (CBRAM) devices exhibit great potential as the next-generation nonvolatile memory devices. However, they suffer from two major disadvantages, namely relatively high power consumption and large cycle-to-cycle and device-to-device variations, which hinder their more extensive commercialization. To learn how to enhance their device performance, kinetic Monte Carlo (KMC) simulations were employed to illustrate the variation of electroforming processes in nanomanipulated CBRAM devices by introducing an ion-blocking layer with scalable nanopores and tuning the microstructures of dielectric layers. Both the size of nanopores and the inhomogeneity of dielectric layers have significant impacts on the forming processes of conductive filaments. The dielectric layer with a high-content loose texture plus the scalable nanopore-containing ion-blocking layer leads to the formation of size-controlled and uniform filaments, which remarkably contributes to miniaturizable and stable CBRAM devices. Our study provides insights into nanomanipulation strategies to realize high-performance CBRAM devices, still awaiting future experimental confirmation.

Construction of PARI public health education programs for Chinese undergraduates: a Delphi study.

Objectives: The objective of this study is to develop a consensus among experts on a comprehensive and scientifically sound physical activity-related injuries (PARI) public health education program specifically tailored for undergraduates. Methods: This study designed three rounds of expert consultation by using a Delphi method. A panel of 30 experts from the fields of public health education, sports medicine, anesthesia pain, emergency medicine, and emergency nursing participated in the study. Results: This study successfully established a consensus among experts on the goals, content, teaching methods, and time allocation for the PARI Public Health Education Program for undergraduates. The program encompasses 10 objectives divided into 2 main categories: professional knowledge and skill goals. In terms of content, it includes 5 primary indicators, 22 secondary indicators, and 56 detailed tertiary indicators. Six teaching methods were identified as suitable. Additionally, a typical 60-min educational session was segmented into eight parts, with a proposed time arrangement for each, ensuring comprehensive coverage of all topics. Conclusion: The consensus achieved in this study on the PARI Public Health Education Program for undergraduates lays a crucial foundation for the advancement of health literacy and proactive health management within this demographic. We presented a comprehensive framework for PARI public health education, integrating diverse learning methods and content areas. This systematic approach not only enriched the resources available for undergraduate health education, especially of PARI but also had the potential to significantly impact the implementation and effectiveness of health promotion strategies.

Multiple factors trigger the formation and resuscitation of the VBNC state in alcohol-producing Klebsiella pneumoniae.

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.

Non-invasive detection of Aspergillosis in ventilated patients: Galactomannan analysis in exhaled breath.

This study evaluates the non-invasive diagnosis of Invasive Aspergillosis Pneumonia (IPA) in mechanically ventilated patients by measuring galactomannan (GM) in exhaled breath condensate (EBC). Utilizing a rat model and a novel EBC collection device, we compared GM levels in bronchoalveolar lavage fluid (BALF) and EBC, supplemented by cytokine profiling. Analysis of 75 patients confirmed the device's efficacy, with EBC-GM and BALF-GM showing high diagnostic accuracy (AUC = 0.88). The threshold of 0.235 ng/ml for EBC-GM achieved 92.8 % sensitivity and 66.7 % specificity, with a strong correlation (r = 0.707, P < 0.001) with BALF-GM. This approach offers a safe, effective alternative to invasive diagnostics, enhancing precision with IL-6 and TNF-α measurements. The number registered on clinicaltrails.gov is NCT06333379.

Pyrenetetrasulfonate-grafted 2D ultrathin metal-organic layer as new electrochemiluminescence emitters for ultrasensitive microRNA-21 assay.

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates. The main reason was that the distance between pyrene rings was greatly expanded after the PyTS grafting on the Zr6 clusters of Zr-BTB-MOL, which overcame the aggregation-caused quenching (ACQ) effect of PyTS and thus enhanced the ECL emission. Meanwhile, the porous nanosheet structure of PyTS-Zr-BTB-MOL could distinctly increase the exposure of PyTS luminophores and shorten the diffusion paths of coreactants and electrons/ions, which effectively promoted the electrochemical excitation of more PyTS luminophores and thus achieved a further ECL enhancement. In light of the remarkable ECL property of PyTS-Zr-BTB-MOL, it was employed as an ECL indicator to build a novel high-sensitivity ECL biosensor for microRNA-21 determination, possessing a satisfactory response range (100 aM to 100 pM) and an ultralow detection limit (10.4 aM). Overall, this work demonstrated that using MOLs to coordinatively graft the PAH derivative luminophores to eliminate the ACQ effect and increase the utilization rate of the luminophores is a promising and efficient strategy to develop high-performance Ru-complex-free ECL materials for assembling ultrasensitive ECL biosensing platforms.

Threonine Aldolase-Catalyzed Enantioselective α-Alkylation of Amino Acids through Unconventional Photoinduced Radical Initiation.

Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.

Glycogen synthase kinase-3ß: A multifaceted player in ischemia-reperfusion injury and its therapeutic prospects.

Ischemia-reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase-3ß (GSK-3ß) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK-3ß provides protection against IRI, making it a viable target for drug development. Though numerous GSK-3ß inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK-3ß roles in IRI. First, we provide an overview of GSK-3ß's basic background. Subsequently, we briefly review the pathological mechanisms of GSK-3ß in accelerating IRI, and highlight the latest progress of GSK-3ß in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK-3ß inhibitors in various organ IRI, offering a thorough and insightful reference for GSK-3ß as a potential target for future IRI therapy.

Eggplant NAC domain transcription factor SmNST1 as an activator promotes secondary cell wall thickening.

NAC-domain transcription factors (TFs) are plant-specific transcriptional regulators playing crucial roles in plant secondary cell wall (SCW) biosynthesis. SCW is important for plant growth and development, maintaining plant morphology, providing rigid support, ensuring material transportation and participating in plant stress responses as a protective barrier. However, the molecular mechanisms underlying SCW in eggplant have not been thoroughly explored. In this study, the NAC domain TFs SmNST1 and SmNST2 were cloned from the eggplant line 'Sanyue qie'. SmNST1 and SmNST2 expression levels were the highest in the roots and stems. Subcellular localization analysis showed that they were localized in the cell membrane and nucleus. Their overexpression in transgenic tobacco showed that SmNST1 promotes SCW thickening. The expression of a set of SCW biosynthetic genes for cellulose, xylan and lignin, which regulate SCW formation, was increased in transgenic tobacco. Bimolecular fluorescence and luciferase complementation assays showed that SmNST1 interacted with SmNST2 in vivo. Yeast one-hybrid, electrophoretic mobility shift assay (EMSA) and Dual-luciferase reporter assays showed that SmMYB26 directly bound to the SmNST1 promoter and acted as an activator. SmNST1 and SmNST2 interact with the SmMYB108 promoter and repress SmMYB108 expression. Altogether, we showed that SmNST1 positively regulates SCW formation, improving our understanding of SCW biosynthesis transcriptional regulation.

AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Facile fabrication of linezolid/strontium coated hydroxyapatite/graphene oxide nanocomposite for osteoporotic bone defect.

Hydroxyapatite (HAp) coatings currently have limited therapeutic applications because they lack anti-infection, osteoinductivity, and poor mechanical characteristics. On the titanium substrate, electrochemical deposition (ECD) was used to construct the strontium (Sr)-featuring hydroxyapatite (HAp)/graphene oxides (GO)/linezolid (LZ) nanomaterial coated with antibacterial and drug delivery properties. The newly fabricated nanomaterials were confirmed by X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analysis and morphological features were examined by scanning electron microscope (SEM) analysis. The results reveal multiple nucleation sites for SrHAp/GO/LZ composite coatings due to oxygen-comprising moieties on the 2D surface of GO. It was shown to be favorable for osteoblast proliferation and differentiation. The elastic modulus and hardness of LZ nanocomposite with SrHAp/GO/LZ coatings were increased by 67 % and 121 %, respectively. An initial 5 h burst of LZ release from the SrHAp/GO/LZ coating was followed by 14 h of gradual release, owing to LZ's physical and chemical adsorption. The SrHAp/GO/LZ coating effectively inhibited both S. epidermidis and S. aureus, and the inhibition lasted for three days, as demonstrated by the inhibition zone and colony count assays. When MG-63 cells are coated with SrHAp/GO/LZ composite coating, their adhesion, proliferation, and differentiation greatly improve when coated with pure titanium. A novel surface engineering nanomaterial for treating and preventing osteoporotic bone defects, SrHAp/GO/LZ, was shown to have high mechanical characteristics, superior antibacterial abilities, and osteoinductivity.

LCGNet: Local Sequential Feature Coupling Global Representation Learning for Functional Connectivity Network Analysis with fMRI.

Analysis of functional connectivity networks (FCNs) derived from resting-state functional magnetic resonance imaging (rs-fMRI) has greatly advanced our understanding of brain diseases, including Alzheimer's disease (AD) and attention deficit hyperactivity disorder (ADHD). Advanced machine learning techniques, such as convolutional neural networks (CNNs), have been used to learn high-level feature representations of FCNs for automated brain disease classification. Even though convolution operations in CNNs are good at extracting local properties of FCNs, they generally cannot well capture global temporal representations of FCNs. Recently, the transformer technique has demonstrated remarkable performance in various tasks, which is attributed to its effective self-attention mechanism in capturing the global temporal feature representations. However, it cannot effectively model the local network characteristics of FCNs. To this end, in this paper, we propose a novel network structure for Local sequential feature Coupling Global representation learning (LCGNet) to take advantage of convolutional operations and self-attention mechanisms for enhanced FCN representation learning. Specifically, we first build a dynamic FCN for each subject using an overlapped sliding window approach. We then construct three sequential components (i.e., edge-to-vertex layer, vertex-to-network layer, and network-to-temporality layer) with a dual backbone branch of CNN and transformer to extract and couple from local to global topological information of brain networks. Experimental results on two real datasets (i.e., ADNI and ADHD-200) with rs-fMRI data show the superiority of our LCGNet.

Acoustofluidics-enhanced biosensing with simultaneously high sensitivity and speed.

Simultaneously achieving high sensitivity and detection speed with traditional solid-state biosensors is usually limited since the target molecules must passively diffuse to the sensor surface before they can be detected. Microfluidic techniques have been applied to shorten the diffusion time by continuously moving molecules through the biosensing regions. However, the binding efficiencies of the biomolecules are still limited by the inherent laminar flow inside microscale channels. In this study, focused traveling surface acoustic waves were directed into an acoustic microfluidic chip, which could continuously enrich the target molecules into a constriction zone for immediate detection of the immune reactions, thus significantly improving the detection sensitivity and speed. To demonstrate the enhancement of biosensing, we first developed an acoustic microfluidic chip integrated with a focused interdigital transducer; this transducer had the ability to capture more than 91% of passed microbeads. Subsequently, polystyrene microbeads were pre-captured with human IgG molecules at different concentrations and loaded for detection on the chip. As representative results, ~0.63, 2.62, 11.78, and 19.75 seconds were needed to accumulate significant numbers of microbeads pre-captured with human IgG molecules at concentrations of 100, 10, 1, and 0.1 ng/mL (~0.7 pM), respectively; this process was faster than the other methods at the hour level and more sensitive than the other methods at the nanomolar level. Our results indicated that the proposed method could significantly improve both the sensitivity and speed, revealing the importance of selective enrichment strategies for rapid biosensing of rare molecules.