Functional Analysis of Insecticide Inhibition and Metabolism of Six Glutathione S-Transferases in the Rice Stem Borer, Chilo suppressalis.

The glutathione S-transferases (GSTs) are important detoxifying enzymes in insects. Our previous studies found that the susceptibility of Chilo suppressalis to abamectin was significantly increased when the CsGST activity was inhibited by glutathione (GSH) depletory. In this study, the potential detoxification mechanisms of CsGSTs to abamectin were explored. Six CsGSTs of C. suppressalis were expressed in vitro. Enzymatic kinetic parameters including Km and Vmax of recombinant CsGSTs were determined, and results showed that all of the six CsGSTs were catalytically active and displaying glutathione transferase activity. Insecticide inhibitions revealed that a low concentration of abamectin could effectively inhibit the activities of CsGSTs including CsGSTd1, CsGSTe4, CsGSTo2, CsGSTs3, and CsGSTu1. However, the in vitro metabolism assay found that the six CsGSTs could not metabolize abamectin directly. Additionally, the glutathione transferase activity of CsGSTs in C. suppressalis was significantly increased post-treatment with abamectin. Comprehensive analysis of the results in present and our previous studies demonstrated that CsGSTs play an important role in detoxification of abamectin by catalyzing the conjugation of GSH to abamectin in C. suppressalis, and the high binding affinities of CsGSTd1, CsGSTe4, CsGSTo2, CsGSTs3, and CsGSTu1 with abamectin might also suggest the involvement of CsGSTs in detoxification of abamectin via the noncatalytic passive binding and sequestration instead of direct metabolism. These studies are helpful to better understand the detoxification mechanisms of GSTs in insects.

An Operating Stiffness Controller for the Medical Continuum Robot Based on Impedance Control.

Continuum manipulators can conform to curvilinear paths and manipulate objects in complex environments, which makes it emerging to be applied in minimally invasive surgery (MIS). However, different and controllable operating stiffness of the continuum manipulator is required during different stages of surgery to achieve safe access or stable and precise operation. This work proposes an operating stiffness controller (OSC) for the typical tendon-driven continuum manipulator based on the variable impedance control method with Lagrangian dynamic modeling. This controller can adjust the operating stiffness by modifying the driving forces along the driving tendons of the continuum manipulator without changing its material or structure. The proposed OSC converts the damping and stiffness matrices of the impedance control into variable parameters. This merit allows it to dynamically adjust the operating stiffness of the continuum manipulator according to the desired constant or time-varying stiffness. Furthermore, the OSC stability can be proven based on a Lyapunov function, and its stiffness control performances have been analyzed and evaluated in both simulations and experiments. The OSC controller generated average relevant error values of 7.82% and 3.09% for the operating stiffness control experiments with constant and time-varying desired stiffness, respectively. These experimental results indicate that the OSC has high accuracy, stability, and strong robustness in the operating stiffness control tasks.

Nature Products Chlorophyll Derivatives for NIR-II Fluorescence Bioimaging and Plant-imaging.

The second near-infrared window (NIR-II, 1000 - 1700 nm) fluorescence imaging has attracted significant attention in research fields because of its unique advantages compared with conventional optical windows (400 - 900 nm). A variety of NIR-II fluorophores have been actively studied because they serve as a key component of fluorescence imaging. Among them, organic small molecule NIR-II fluorophores display outstanding imaging performance and many advantages, but types of small molecule NIR-II fluorophores with high biocompatibility are still quite limited. Novel molecular scaffolds based NIR-II dyes are highly desired. Herein, we hypothesized that chlorophyll is a new promising molecular platform for discovery NIR-II fluorophores. Thus, seven derivatives of derivatives were selected to characterize their optical properties. Interestingly, six chlorophyll derivatives displayed NIR-II fluorescence imaging capability. This characteristic allowed the successful NIR-II imaging of green leaves of various plants. Furthermore, most of these fluorophores showed capacity to monitor viscosity change because of their sensitive for viscosity. For demonstration of its biomedical applications, these probes were successfully used for NIR-II fluorescence-guided surgical resection of lymph nodes. In summary, chlorophylls are novel valuable tool molecules for NIR-II fluorescence imaging and have potential to expand their applications in biomedical field and plant science.

Heart Sound Abnormality Detection From Multi-Institutional Collaboration: Introducing a Federated Learning Framework.

OBJECTIVE: Early diagnosis of cardiovascular diseases is a crucial task in medical practice. With the application of computer audition in the healthcare field, artificial intelligence (AI) has been applied to clinical non-invasive intelligent auscultation of heart sounds to provide rapid and effective pre-screening. However, AI models generally require large amounts of data which may cause privacy issues. Unfortunately, it is difficult to collect large amounts of healthcare data from a single centre. METHODS: In this study, we propose federated learning (FL) optimisation strategies for the practical application in multi-centre institutional heart sound databases. The horizontal FL is mainly employed to tackle the privacy problem by aligning the feature spaces of FL participating institutions without information leakage. In addition, techniques based on deep learning have poor interpretability due to their "black-box" property, which limits the feasibility of AI in real medical data. To this end, vertical FL is utilised to address the issues of model interpretability and data scarcity. CONCLUSION: Experimental results demonstrate that, the proposed FL framework can achieve good performance for heart sound abnormality detection by taking the personal privacy protection into account. Moreover, using the federated feature space is beneficial to balance the interpretability of the vertical FL and the privacy of the data. SIGNIFICANCE: This work realises the potential of FL from research to clinical practice, and is expected to have extensive application in the federated smart medical system.

Instant interaction driven adaptive gaze control interface.

Gaze estimation is long been recognised as having potential as the basis for human-computer interaction (HCI) systems, but usability and robustness of performance remain challenging . This work focuses on systems in which there is a live video stream showing enough of the subjects face to track eye movements and some means to infer gaze location from detected eye features. Currently, systems generally require some form of calibration or set-up procedure at the start of each user session. Here we explore some simple strategies for enabling gaze based HCI to operate immediately and robustly without any explicit set-up tasks. We explore different choices of coordinate origin for combining extracted features from multiple subjects and the replacement of subject specific calibration by system initiation based on prior models. Results show that referencing all extracted features to local coordinate origins determined by subject start position enables robust immediate operation. Combining this approach with an adaptive gaze estimation model using an interactive user interface enables continuous operation with the 75th percentile gaze errors of 0.7 ∘ , and maximum gaze errors of 1.7 ∘ during prospective testing. There constitute state-of-the-art results and have the potential to enable a new generation of reliable gaze based HCI systems.

Magnesium oxide nanoparticles reduce clubroot by regulating plant defense response and rhizosphere microbial community of tumorous stem mustard (Brassica juncea var. tumida).

Clubroot, caused by Plasmodiophora brassicae, is a major disease that significantly impairs the yield of cruciferous crops and causes significant economic losses across the globe. The prevention of clubroot, especially in tumorous stem mustard (without resistant varieties), are is limited and primarily relies on fungicides. Engineered nanoparticles have opened up new avenues for the management of plant diseases, but there is no report on their application in the prevention of clubroot. The results showed that the control efficacy of 500 mg/L MgO NPs against clubroot was 54.92%. However, when the concentration was increased to 1,500 and 2,500 mg/L, there was no significant change in the control effect. Compared with CK, the average fresh and dry weight of the aerial part of plants treated with MgO NPs increased by 392.83 and 240.81%, respectively. Compared with the F1000 treatment, increases were observed in the content of soil available phosphorus (+16.72%), potassium (+9.82%), exchangeable magnesium (+24.20%), and water-soluble magnesium (+20.64%) in the 1,500 mg/L MgO NPs treatment. The enzyme-linked immune sorbent assay (ELISA) results showed that the application of MgO NPs significantly increased soil peroxidase (POD, +52.69%), alkaline protease (AP, +41.21%), alkaline phosphatase (ALP, +79.26%), urease (+52.69%), and sucrase (+56.88%) activities; And also increased plant L-phenylalanine ammonla-lyase (PAL, +70.49%), polyphenol oxidase (PPO, +36.77%), POD (+38.30%), guaiacol peroxidase (POX, +55.46%) activities and salicylic acid (SA, +59.86%) content. However, soil and plant catalase (CAT, -27.22 and - 19.89%, respectively), and plant super oxidase dismutase (SOD, -36.33%) activities were significantly decreased after the application of MgO NPs. The metagenomic sequencing analysis showed that the MgO NPs treatments significantly improved the α-diversity of the rhizosphere soil microbial community. The relative abundance of beneficial bacteria genera in the rhizosphere soil, including Pseudomonas, Sphingopyxis, Acidovorax, Variovorax, and Bosea, was significantly increased. Soil metabolic functions, such as oxidative phosphorylation (ko00190), carbon fixation pathways in prokaryotes (ko00720), indole alkaloid biosynthesis (ko00901), and biosynthesis of various antibiotics (ko00998) were significantly enriched. These results suggested that MgO NPs might control clubroot by promoting the transformation and utilization of soil nutrients, stimulating plant defense responses, and enriching soil beneficial bacteria.

Pt/NiFe-LDH hybrids for quantification and qualification of polyphenols.

Polyphenols with antioxidant properties are of significant interest in medical and pharmaceutical applications. Given the diverse range of activities of polyphenols in vivo, accurate detection of these compounds plays a crucial role in nutritional surveillance and pharmaceutical development. Yet, the efficient quantitation of polyphenol contents and qualification of monomer compositions present a notable challenge when studying polyphenol bioavailability. In this study, platinum-modified nickel-iron layered double hydroxide (Pt/NiFe-LDH hybrids) were designed to mimic peroxidases for colorimetric analysis and act as enhanced matrices for laser desorption/ionization mass spectrometry (LDI MS) to quantify and qualify polyphenols. The hybrids exhibited an enzymatic activity of 33.472 U/mg for colorimetric assays, facilitating the rapid and direct quantitation of total tea polyphenols within approximately 1 min. Additionally, the heterogeneous structure and exposed hydroxyl groups on the hybrid surface contributed to photoelectric enhancement and in-situ enrichment of polyphenols in LDI MS. This study introduces an innovative approach to detect polyphenols using advanced materials, potentially inspiring the future development and applications of other photoactive nanomaterials.

Regulation of Wnt/ß-catenin signaling by Marek's disease virus in vitro and in vivo.

Marek's disease virus (MDV) infection causes immunosuppression in the host, ultimately inducing tumor formation and causing significant economic losses to the poultry industry. While the abnormal activation of the Wnt/ß-catenin signaling pathway is closely associated with the occurrence and development of tumors. However, the relationship between MDV and the Wnt/ß-catenin pathway remains unclear. In this study, we found that the MDV RB1B strain, but not the MDV vaccine strain CVI988, activated the Wnt/ß-catenin signaling pathway by increasing the phosphorylation level of GSK-3ß in chicken embryo fibroblast (CEF). In vivo infection experiments in SPF chickens also confirmed that the RB1B strain activated the Wnt/ß-catenin signaling pathway, while the CVI988 strain did not lead to its activation. Moreover, unlike the Meq protein encoded by the CVI988 strain, the Meq protein encoded by the RB1B strain specifically activated the Wnt/ß-catenin signaling pathway in CEF cells. The findings from these studies extend our understanding of the regulation of Wnt/ß-catenin signaling by MDV, which make a new contribution to understanding the virus-host interactions of MDV.

Metabolomics analysis of CEF cells infected with avian leukosis virus subgroup J based on UHPLC-QE-MS.

Avian leukosis virus subgroup J (ALV-J) is a retrovirus that can cause immunosuppression and tumors in chicken. However, relative pathogenesis is still not clear. At present, metabolomics has shown great potential in the screening of tumor metabolic markers, prognostic evaluation, and drug target design. In this study, we utilize an untargeted metabolomics approach based on ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) to analyze the metabolic changes in chicken embryo fibroblast (CEF) cells infected by ALV-J. We found that ALV-J infection significantly altered a wealth of metabolites compared with control group. Additionally, most of the differentially expressed metabolites belonged to lipid metabolism, purine nucleotide metabolism and amino acid metabolism. Among them, the proportion of lipid metabolites account for the highest proportion (around 31%). Results suggest that these changes may be conductive to the formation of virion, thereby promoting the replication of ALV-J. These data provided metabolic evidence and potential biomarkers for the cellular metabolic changes induced by ALV-J, and provided important insight for further understanding the replication needs and pathogenesis of ALV-J.

Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis.

BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.

Comparison of three frailty scales for prediction of prolonged postoperative ileus following major abdominal surgery in elderly patients: a prospective cohort study.

BACKGROUND: To determine whether frailty can predict prolonged postoperative ileus (PPOI) in older abdominal surgical patients; and to compare predictive ability of the FRAIL scale, the five-point modified frailty index (mFI-5) and Groningen Frailty Indicator (GFI) for PPOI. METHODS: Patients (aged ≥ 65 years) undergoing major abdominal surgery at our institution between April 2022 to January 2023 were prospectively enrolled. Frailty was evaluated with FRAIL, mFI-5 and GFI before operation. Data on demographics, comorbidities, perioperative management, postoperative recovery of bowel function and PPOI occurrence were collected. RESULTS: The incidence of frailty assessed with FRAIL, mFI-5 and GFI was 18.2%, 38.4% and 32.5% in a total of 203 patients, respectively. Ninety-five (46.8%) patients experienced PPOI. Time to first soft diet intake was longer in patients with frailty assessed by the three scales than that in patients without frailty. Frailty diagnosed by mFI-5 [Odds ratio (OR) 3.230, 95% confidence interval (CI) 1.572-6.638, P = 0.001] or GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) was related to a higher risk of PPOI. Both mFI-5 [Area under curve (AUC) 0.653, 95% CI 0.577-0.730] and GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) had insufficient accuracy for the prediction of PPOI in patients undergoing major abdominal surgery. CONCLUSIONS: Elderly patients diagnosed as frail on the mFI-5 or GFI are at an increased risk of PPOI after major abdominal surgery. However, neither mFI-5 nor GFI can accurately identify individuals who will develop PPOI. TRIAL REGISTRATION: This study was registered in Chinese Clinical Trial Registry (No. ChiCTR2200058178). The date of first registration, 31/03/2022, https://www.chictr.org.cn/ .

Low concentrations of cyantraniliprole negatively affects the development of Spodoptera frugiperda by disruption of ecdysteroid biosynthesis and carbohydrate and lipid metabolism.

In addition to the acute lethal toxicity, insecticides might affect population dynamics of insect pests by inducing life history trait changes under low concentrations, however, the underlying mechanisms remain not well understood. Here we examined systemic impacts on development and reproduction caused by low concentration exposures to cyantraniliprole in the fall armyworm (FAW), Spodoptera frugiperda, and the putative underlying mechanisms were investigated. The results showed that exposure of third-instar larvae to LC10 and LC30 of cyantraniliprole significantly extended larvae duration by 1.46 and 5.41 days, respectively. Treatment with LC30 of cyantraniliprole significantly decreased the pupae weight and pupation rate as well as the longevity, fecundity and egg hatchability of female adults. Consistently, we found that exposure of FAW to LC30 cyantraniliprole downregulated the mRNA expression of four ecdysteroid biosynthesis genes including SfNobo, SfShd, SfSpo and SfDib and one ecdysone response gene SfE75 in the larvae as well as the gene encoding vitellogenin (SfVg) in the female adults. We also found that treatment with LC30 of cyantraniliprole significantly decreased the whole body levels of glucose, trehalose, glycogen and triglyceride in the larvae. Our results indicate that low concentration of cyantraniliprole inhibited FAW development by disruption of ecdysteroid biosynthesis as well as carbohydrate and lipid metabolism, which have applied implications for the control of FAW.

Integrating Machine Learning in Metabolomics: A Path to Enhanced Diagnostics and Data Interpretation.

Metabolomics, leveraging techniques like NMR and MS, is crucial for understanding biochemical processes in pathophysiological states. This field, however, faces challenges in metabolite sensitivity, data complexity, and omics data integration. Recent machine learning advancements have enhanced data analysis and disease classification in metabolomics. This study explores machine learning integration with metabolomics to improve metabolite identification, data efficiency, and diagnostic methods. Using deep learning and traditional machine learning, it presents advancements in metabolic data analysis, including novel algorithms for accurate peak identification, robust disease classification from metabolic profiles, and improved metabolite annotation. It also highlights multiomics integration, demonstrating machine learning's potential in elucidating biological phenomena and advancing disease diagnostics. This work contributes significantly to metabolomics by merging it with machine learning, offering innovative solutions to analytical challenges and setting new standards for omics data analysis.

Pancreatic cyst prevalence and detection with photon counting CT compared with conventional energy integrating detector CT.

PURPOSE: To calculate the prevalence of pancreatic cysts on photon counting CT (PCCT) and compare with that of 128-slice conventional energy-integrating detector CT (EIDCT). METHOD: A retrospective single institution database search identified all contrast-enhanced abdominal CT examinations performed at an outpatient facility that has both a PCCT and EIDCT between 4/11/2022 and 7/26/2022. The presence and size of pancreatic cysts were recorded. In patients with PCCT reported pancreatic cysts, prior CT imaging (EIDCT) was reviewed for reported pancreatic cysts. Fisher's exact test was used to compare the pancreatic cyst detection rate for PCCT and EIDCT. Wilcoxon rank sum test was used to compare cyst size and patient age. A p <.05 indicated statistical significance. RESULTS: 2494 patients were included. Our pancreatic cyst detection rate was 4.9 % (49/1009) with PCCT and 3.0 % (44/1485) for EIDCT (p =.017). For CT angiograms, pancreatic cysts were detected in 6.6 % (21/319) with PCCT and 0.0 % (0/141) with EIDCT (p <.001). Pancreatic cyst detection rate was not statistically different for portal venous, enterography, renal mass, pancreas, 3-phase liver, or venogram protocols (all p >.05). Mean[SD] pancreatic cyst size was 13.7[9.7]mm for PCCT and 15.3[14.7] for EIDCT (p =.95). 55.1 % (27/49) of PCCT and 61.4 % (27/44) of EIDCT that described pancreatic cysts had prior contrast-enhanced EIDCTs. Of these, 40.7 % (11/27) of PCCT and 14.8 % (4/27) of EIDCT described pancreatic cysts were not previously reported (p =.027). CONCLUSIONS: Photon-counting CT afforded greater pancreatic cyst detection than conventional energy-integrating detector CT, particularly with CT angiograms.

Clinical Outcomes of Ileostomy Closure during versus after Adjuvant Chemotherapy in Patients with Rectal Cancer.

Background: Protective ileostomy can effectively prevent severe anastomotic leakage after rectal cancer surgery; however, the optimal timing for ileostomy closure during adjuvant chemotherapy remains unclear. This study aimed to explore the safety and long-term outcomes of early ileostomy closure during adjuvant chemotherapy. Method: Patients who underwent laparoscopic rectal cancer surgery combined with protective ileostomy and adjuvant chemotherapy between April 2017 and April 2021 were retrospectively evaluated. Patients were divided into an early closure group during chemotherapy (group A) and a late closure group after chemotherapy (group B). Results: A total of 215 patients were included in this study, with 115 in group A and 100 in group B. There were no significant differences in demographic and clinical characteristics between the two groups. In group A, durations of stoma status (p < 0.001) and low anterior resection syndrome (LARS) (p < 0.001) were shorter, and rectal stenosis (p=0.036) and stoma-related complications (p=0.007), especially stoma stenosis (p=0.041), were less common. However, compliance with chemotherapy was worse (p=0.009). There were no significant differences in operative time, postoperative hospital stay, postoperative complications, incidence and severity of LARS, disease-free survival, or overall survival between groups. Conclusion: Early ileostomy closure can effectively reduce the duration of stoma status, duration of LARS, rectal stenosis, and stoma-related complications while not affecting surgical complications and oncological outcomes. Ileostomy closure should not be delayed because of adjuvant chemotherapy. However, follow-up should be strengthened to increase compliance and integrity with chemotherapy.

Integration of scRNA-seq data by disentangled representation learning with condition domain adaptation.

BACKGROUND: The integration of single-cell RNA sequencing data from multiple experimental batches and diverse biological conditions holds significant importance in the study of cellular heterogeneity. RESULTS: To expedite the exploration of systematic disparities under various biological contexts, we propose a scRNA-seq integration method called scDisco, which involves a domain-adaptive decoupling representation learning strategy for the integration of dissimilar single-cell RNA data. It constructs a condition-specific domain-adaptive network founded on variational autoencoders. scDisco not only effectively reduces batch effects but also successfully disentangles biological effects and condition-specific effects, and further augmenting condition-specific representations through the utilization of condition-specific Domain-Specific Batch Normalization layers. This enhancement enables the identification of genes specific to particular conditions. The effectiveness and robustness of scDisco as an integration method were analyzed using both simulated and real datasets, and the results demonstrate that scDisco can yield high-quality visualizations and quantitative outcomes. Furthermore, scDisco has been validated using real datasets, affirming its proficiency in cell clustering quality, retaining batch-specific cell types and identifying condition-specific genes. CONCLUSION: scDisco is an effective integration method based on variational autoencoders, which improves analytical tasks of reducing batch effects, cell clustering, retaining batch-specific cell types and identifying condition-specific genes.

(Z, Z, Z)-3,6,9-Nonadecadiene, a potential inhibitor of sex pheromone of Grey Tea Geometrid (Lepidoptera: Geometridae): electroantennogram test, wind tunnel, and in silico study.

Sex pheromone analogs have high structural similarity to sex pheromone components. They also play a role in studying many agricultural pests. In our study, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy) was successfully synthesized, which is an analogue to 1 of 2 sex pheromone components of Ectropis grisescens Warren (Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), and it showed potential inhibition in experiments. In the electroantennogram test, Z3Z6Z9-19:Hy showed a dose-dependent response, and only measured half the response of Z3Z9-6,7-epo-18:Hy. However, the compound significantly reduced positive response of E. grisescens males by up to 70% in the Y-tube olfactometer. Furthermore, in the wind tunnel, it significantly inhibited all types of behavioral responses. The percentage of moths contacting the pheromone odor source was reduced even at the lowest dose tested. In silico study afterward, molecular docking results showed affinity between Z3Z6Z9-19:Hy and sensory neuron membrane protein 1. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new tools for monitoring and mating disruption of E. grisescens.

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho-1/Gpx4 pathway to prevent α-synuclein-induced ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

Integrating Paper-Based Microfluidics and Lateral Flow Strip into Nucleic Acid Amplification Device toward Rapid, Low-Cost, and Visual Diagnosis of Multiple Mycobacteria.

Efficient diagnosis of mycobacterial infections can effectively manage and prevent the transmission of infectious diseases. Unfortunately, existing diagnostic strategies are challenged by long assay times, high costs, and highly specialized expertise to distinguish between pulmonary tuberculosis (PTB) and nontuberculous mycobacterial pulmonary diseases (NTM-PDs). Herein, in this study, an optimized 3D paper-based analytical device (µPAD) is incorporated with a closed lateral flow (LF) strip into a loop-mediated isothermal amplification (LAMP) device (3D-µPAD-LF-LAMP) for rapid, low-cost, and visual detection of pathogenic mycobacteria. The platform's microfluidic feature enhanced the nucleic acid amplification, thereby reducing the costs and time as compared to boiling, easyMAG, and QIAGEN techniques. Moreover, the LF unit is specifically designed to minimize aerosol contamination for a user-friendly and visual readout. 3D-µPAD-LF-LAMP is optimized and assessed using standard strains, demonstrating a limit of detection (LOD) down to 10 fg reaction-1 . In a cohort of 815 patients, 3D-µPAD-LF-LAMP displays significantly better sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy than conventional bacterial culture and Xpert techniques. Collectively, 3D-µPAD-LF-LAMP demonstrates enhanced accessibility, efficiency, and practicality for the diagnosis of multiple pathogenic mycobacteria, which can be applied across diverse clinical settings, thereby ultimately improving public health outcomes.

Plasmonic Alloys Enhanced Metabolic Fingerprints for the Diagnosis of COPD and Exacerbations.

Accurate diagnosis of chronic obstructive pulmonary disease (COPD) and exacerbations by metabolic biomarkers enables individualized treatment. Advanced metabolic detection platforms rely on designed materials. Here, we design mesoporous PdPt alloys to characterize metabolic fingerprints for diagnosing COPD and exacerbations. As a result, the optimized PdPt alloys enable the acquisition of metabolic fingerprints within seconds, requiring only 0.5 µL of native plasma by laser desorption/ionization mass spectrometry owing to the enhanced electric field, photothermal conversion, and photocurrent response. Machine learning decodes metabolic profiles acquired from 431 individuals, achieving a precise diagnosis of COPD with an area under the curve (AUC) of 0.904 and an accurate distinction between stable COPD and acute exacerbations of COPD (AECOPD) with an AUC of 0.951. Notably, eight metabolic biomarkers identified accurately discriminate AECOPD from stable COPD while providing valuable information on disease progress. Our platform will offer an advanced nanoplatform for the management of COPD, complementing standard clinical techniques.