The mechanism of intrinsic peroxidase (POD)-like activity of attapulgite.

Natural attapulgite (ATP) is a promising substitute for existing artificial nanozymes due to its intrinsic enzymatic activity. However, the active center of ATP's inherent enzymatic activity has not yet been revealed, which limits its further design and activity optimization. Studying the active center of mineral materials can be extremely challenging due to their complexity. Here, we demonstrated that Fe is the primary element in ATP responsible for peroxidase (POD)-like activity through theoretical speculation and experimental verification. More importantly, we found that the ratio of Fe2+/Fe3+ is responsible for the district POD-like activity of ATP from different regions with the same Fe content. Additionally, three facile strategies, including grinding, heat treatment, and acid treatment, were demonstrated to increase the relative Fe content and thus optimize the POD-like activity of ATP. Finally, ATP was used to detect the concentration of H2O2, enabling the detection of low concentrations (0.11-1.76 mM) of H2O2. This study serves as a novel reference for the future design and performance optimization of nanozymes that are based on ATP and clay minerals.

VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response.

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens.

A receptor required for chitin perception facilitates arbuscular mycorrhizal associations and distinguishes root symbiosis from immunity.

Plants establish symbiotic associations with arbuscular mycorrhizal fungi (AMF) to facilitate nutrient uptake, particularly in nutrient-limited conditions. This partnership is rooted in the plant's ability to recognize fungal signaling molecules, such as chitooligosaccharides (chitin) and lipo-chitooligosaccharides. In the legume Medicago truncatula, chitooligosaccharides trigger both symbiotic and immune responses via the same lysin-motif-receptor-like kinases (LysM-RLKs), notably CERK1 and LYR4. The nature of plant-fungal engagement is opposite according to the outcomes of immunity or symbiosis signaling, and as such, discrimination is necessary, which is challenged by the dual roles of CERK1/LYR4 in both processes. Here, we describe a LysM-RLK, LYK8, that is functionally redundant with CERK1 for mycorrhizal colonization but is not involved in chitooligosaccharides-induced immunity. Genetic mutation of both LYK8 and CERK1 blocks chitooligosaccharides-triggered symbiosis signaling, as well as mycorrhizal colonization, but shows no further impact on immunity signaling triggered by chitooligosaccharides, compared with the mutation of CERK1 alone. LYK8 interacts with CERK1 and forms a receptor complex that appears essential for chitooligosaccharides activation of symbiosis signaling, with the lyk8/cerk1 double mutant recapitulating the impact of mutations in the symbiosis signaling pathway. We conclude that this novel receptor complex allows chitooligosaccharides activation specifically of symbiosis signaling and helps the plant to differentiate between activation of these opposing signaling processes.

Microstructural abnormality of white matter tracts in rheumatoid arthritis.

BACKGROUND: Structural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. OBJECTIVES: To automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. METHODS: This single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. RESULTS: Compared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. CONCLUSIONS: We report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Comparing massa medicata fermentata before and after charred in terms of digestive promoting effect via metabolomics and microbiome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Massa Medicata Fermentata, a fermented Chinese medicine, is produced by the fermentation of six traditional Chinese medicines. Liu Shenqu (LSQ) and charred Liu Shenqu (CLSQ) have been used for strengthening the spleen and enhancing digestion for over a thousand years, and CLSQ is commonly used in clinical practice. However, it is unclear whether there is a difference in the spleen strengthening and digestion effects between LSQ and CLSQ, as well as their mechanisms of action. AIM OF STUDY: This study aims to compare the effects of LSQ and CLSQ on the digestive function of functional dyspepsia (FD) rats and reveal their mechanisms of action. MATERIALS AND METHODS: SPF grade SD rats were randomly divided into 6 groups: control group, model group, Liu Shenqu decoction low-dosage (LSQ LD) group, Liu Shenqu decoction high-dosage (LSQ HD) group, charred Liu Shenqu decoction low-dosage (CLSQ LD) group, and charred Liu Shenqu decoction high-dosage (CLSQ HD) group. Rats were injected intraperitoneally with reserpine to create an FD model and then treated by intragastric administration. During this period, record the weight and food intake of the animals. After 18 days of treatment, specimens of the gastric antrum, spleen, and duodenum of rats were taken for pathological staining and immunohistochemical detection of Ghrelin protein expression. Enzyme linked immunosorbent assay (ELISA) was used to determine the concentration of relevant gastrointestinal hormones in serum. The 16 S rDNA sequencing method was used to evaluate the effect of cecal contents on the structure of the gut microbiota in experimental rats. Plasma metabolomics analysis was performed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) to further reveal their mechanism of action. RESULTS: LSQ and CLSQ improved the pathological tissue histological structure of FD rats and increased the levels of MTL and GAS hormones in serum and the levels of ghrelin in the gastric antrum, spleen, and duodenum, while reducing VIP, CCK, and SP hormone levels. The above results showed that the therapeutic efficacy of CLSQ is better than that of LSQ. Futhermore, the mechanism of action of LSQ and CLSQ were revealed. The 16 S rDNA sequencing results showed that both LSQ and CLSQ can improve the composition and diversity of the gut microbiota. And metabolomic analysis demonstrated that 20 metabolites changed after LSQ treatment, and 16 metabolites underwent continuous changes after CLSQ treatment. Further analysis revealed that LSQ mainly intervened in the metabolic pathways of glycerol phospholipid metabolism and arginine and proline metabolism, but CLSQ mainly intervened in the metabolic pathways of ether lipid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. CONCLUSIONS: Both LSQ and CLSQ can improve functional dyspepsia in FD rats, but CLSQ has a stronger improvement effect on FD. Although their mechanisms of action are all related to regulating gastrointestinal hormone secretion, significantly improving intestinal microbiota disorders, and improving multiple metabolic pathways, but the specific gut microbiota and metabolic pathways they regulate are different.

Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane.

Most recently, worldwide interest in butyrylcholinesterase (BChE) as a potential target for treating Alzheimer's disease (AD) has increased. In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 µM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC0-inf = 1729.95 ng/mL*h, upgraded by 2.6 times) and oral bioavailability (Fpo = 48.18%, upgraded by 2 times). S16-1029 also displayed weak or no inhibition against Cytochrome P450 (CYP450) and human ether a-go-go related gene (hERG) potassium channel. In vivo experiments on tissue distribution revealed that S16-1029 could cross the blood-brain barrier (BBB) and reach the central nervous system (CNS). In vivo cognitive improvement efficacy and good in vitro target inhibitory activity (eqBChE IC50 = 11.35 ± 4.84 nM, hBChE IC50 = 48.1 ± 11.4 nM) were also assured. The neuroprotective effects against several AD pathology characteristics allowed S16-1029 to successfully protect the CNS of progressed AD patients. According to the findings of this study, altering molecular planarity might be a viable strategy for improving the drug-like property of CNS-treating drugs.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.

Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for In Vivo Theranostics of Alzheimer's Disease.

Butyrylcholinesterase (BChE) is a promising biomarker and effective therapeutic target for Alzheimer's disease (AD). Herein, we designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE inhibitor as the therapeutic unit. DTNP specifically binds BChE with high sensitivity and exhibits strong "turn-on" NIR fluorescence as well as nerve cell protection. In vivo imaging shows DTNP has favorable blood-brain barrier permeability and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the release of ACh, and rescue learning deficits and cognitive impairment. Therefore, DTNP, the first reported and partially validated theranostic probe for the detection of BChE in AD, may provide a foundation and inspiration for imaging and therapy in AD.

The Effect P Additive on the CeZrAl Support Properties and the Activity of the Pd Catalysts in Propane Oxidation.

The properties of a catalyst support are closely related to the catalyst activity, yet the focus is often placed on the active species, with little attention given to the support properties. In this work, we specifically investigated the changes in support properties after the addition of P, as well as their impact on catalyst activity when used for catalyst preparation. We prepared the CeO2-ZrO2-P2O5-Al2O3 (CeZrPAl) composite oxides using the sol-gel, impregnation, and mechanical mixing methods, and characterized the support properties using techniques such as XRD, XPS, SEM-EDS, N2 adsorption-desorption, and Raman spectra. The results showed that the support prepared using the sol-gel method can exhibit a more stable phase structure, larger surface area, higher adsorption capacity for oxygen species, and greater oxygen storage capacity. The addition of an appropriate amount of P is necessary. On the one hand, the crystallization and growth of CePO4 can lead to a decrease in the Ce content in the cubic phase ceria-zirconia solid solution, resulting in a phase separation of the ceria-zirconia solid solution. On the other hand, CePO4 can lock some of the Ce3+/Ce4+ redox pairs, leading to a reduction in the adsorption of oxygen species and a decrease in the oxygen storage capacity of the CeZrPAl composite oxides. The research results indicated that the optimal P addition is 6 wt.% in the support. Therefore, we prepared a Pd/CeZrPAl catalyst using CeZrAl with 6 wt.% P2O5 as the support and conducted the catalytic oxidation of C3H8. Compared with the support without P added, the catalyst activity of the support loaded with P was significantly improved. The fresh and aged (1000 °C/5 h) catalysts decreased by 20 °C and 5 °C in T50 (C3H8 conversion temperature of 50%), and by 81 °C and 15 °C in T90 (C3H8 conversion temperature of 90%), respectively.

Sound-evoked adenosine release in cooperation with neuromodulatory circuits permits auditory cortical plasticity and perceptual learning.

Meaningful auditory memories are formed in adults when acoustic information is delivered to the auditory cortex during heightened states of attention, vigilance, or alertness, as mediated by neuromodulatory circuits. Here, we identify that, in awake mice, acoustic stimulation triggers auditory thalamocortical projections to release adenosine, which prevents cortical plasticity (i.e., selective expansion of neural representation of behaviorally relevant acoustic stimuli) and perceptual learning (i.e., experience-dependent improvement in frequency discrimination ability). This sound-evoked adenosine release (SEAR) becomes reduced within seconds when acoustic stimuli are tightly paired with the activation of neuromodulatory (cholinergic or dopaminergic) circuits or periods of attentive wakefulness. If thalamic adenosine production is enhanced, then SEAR elevates further, the neuromodulatory circuits are unable to sufficiently reduce SEAR, and associative cortical plasticity and perceptual learning are blocked. This suggests that transient low-adenosine periods triggered by neuromodulatory circuits permit associative cortical plasticity and auditory perceptual learning in adults to occur.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

Growing attention on the toxicity of Chinese herbal medicine: a bibliometric analysis from 2013 to 2022.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM's toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade. Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations. Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019-2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology. Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

A multicenter study: predicting KRAS mutation and prognosis in colorectal cancer through a CT-based radiomics nomogram.

PURPOSE: To establish a CT-based radiomics nomogram for preoperative prediction of KRAS mutation and prognostic stratification in colorectal cancer (CRC) patients. METHODS: In a retrospective analysis, 408 patients with confirmed CRC were included, comprising 168 cases in the training set, 111 cases in the internal validation set, and 129 cases in the external validation set. Radiomics features extracted from the primary tumors were meticulously screened to identify those closely associated with KRAS mutation. Subsequently, a radiomics nomogram was constructed by integrating these radiomics features with clinically significant parameters. The diagnostic performance was assessed through the area under the receiver operating characteristic curve (AUC). Lastly, the prognostic significance of the nomogram was explored, and Kaplan-Meier analysis was employed to depict survival curves for the high-risk and low-risk groups. RESULTS: A radiomics model was constructed using 19 radiomics features significantly associated with KRAS mutation. Furthermore, a nomogram was developed by integrating these radiomics features with two clinically significant parameters (age, tumor location). The nomogram achieved AUCs of 0.834, 0.813, and 0.811 in the training set, internal validation set, and external validation set, respectively. Additionally, the nomogram effectively stratified patients into high-risk (KRAS mutation) and low-risk (KRAS wild-type) groups, demonstrating a significant difference in overall survival (P < 0.001). Patients categorized in the high-risk group exhibited inferior overall survival in contrast to those classified in the low-risk group. CONCLUSIONS: The CT-based radiomics nomogram demonstrates the capability to effectively predict KRAS mutation in CRC patients and stratify their prognosis preoperatively.

Advanced researches of traditional uses, phytochemistry, pharmacology, and toxicology of medical Uncariae Ramulus Cum Uncis.

ETHNOPHARMACOLOGICAL RELEVANCE: Medical Uncariae Ramulus Cum Uncis consists of Uncaria rhynchophylla (Miq.) Miq. ex Havil, Uncaria macrophylla Wall, Uncaria sinensis (Oliv.) Havil, Uncaria hirsuta Havil, and Uncaria sessilifructus Roxb, which belongs to the species widely used in the genus Uncaria. These species resource widely distributed in China and abroad, and the hook-bearing stem is the primary constituent enrichment site. There are many different forms and architectures of chemicals, depending on the extraction site. Traditional remedies employing URCU had been used widely in antiquity and were first compiled in renowned ancient masterpiece 'Mingyi Bielu ()' written by Hongjing Tao. In modern pharmacological studies, both the total extracts and the phytoconstituents isolated from URCU have been shown to have neuroprotective, antioxidant, anti-inflammatory, anticancer, antibacterial, and autophagy-enhancer properties. AIM OF THE STUDY: This review concentrates on the traditional uses, phytochemistry, pharmacology, toxicology, and nanomaterials studies of URCU, with a perspective to assist with further research and advance. MATERIAL AND METHODS: The Chinese and English literature studies of this review are based on these database searches including Science Direct, CNKI, Wiley online library, Spring Link, Web of Science, PubMed, Medalink, Google scholar, Elsevier, ACS Publications, iPlant, Missouri Botanical Garden, Plant of the World Online. The pertinent data on URCU was gathered. RESULTS: Based on the examination of the genus Uncaria, 107 newly marked chemical compositions have been identified from URCU from 2015 to present, including alkaloids, terpenoids, flavonoids, steroids, and others. Pharmacological studies have demonstrated that URCU has a variety of benefits in diseases such as neurodegenerative diseases, cancer, cardiovascular diseases, diabetes, and migraine, due to its neuroprotective, anti-inflammatory, antioxidant, anti-tumor, anti-bacterial and anti-viral properties. According to metabolic and toxicological studies, the dosage, frequency, and interactions of the drugs that occur in vivo are of great significance for determining whether the organic bodies can perform efficacy or produce toxicity. The research on URCU-mediated nanomaterials is expanding and increasing in order to address the inadequacies of conventional Chinese medicine. The alkaloids in URCU have the capability to self-assemble with other classes of components in addition to being biologically active. CONCLUSION: URCU plants are widely distributed, abundant in chemical constituents, and widely used in both traditional and modern medicine for a variety of pharmacological effects. The utilization of herbal medicines can be raised by assessing the pharmacological distinctions among several species within the same genus and may accelerate the modernization of traditional Chinese medicine. Controlling the concentration of drug administration, monitoring metabolic markers, and inventing novel nanotechnologies are effective strategies for synergistic influence and detoxification to alleviate the main obstacles that toxicity, low bioavailability, and poor permeability. This review can assist further research and advances.

Force-Encoding DNA Nanomachines for Simultaneous and Direct Detection of Multiple Pathogenic Bacteria in Blood.

Pathogen detection is growing in importance in the early stages of bacterial infection and treatment due to the significant morbidity and mortality associated with bloodstream infections. Although various diagnostic approaches for pathogen detection have been proposed, most of them are time-consuming, with insufficient sensitivity and limited specificity and multiplexing capability for clinical use. Here, we report a force-encoding DNA nanomachine for simultaneous and high-throughput detection of multiple pathogens in blood through force-induced remnant magnetization spectroscopy (FIRMS). The force-encoding DNA nanomachines coupled with DNA walkers enable analytical sensitivity down to a single bacterium via a cascade signal amplification strategy. More importantly, it allows for rapid and specific profiling of various pathogens directly in blood samples, without being affected by factors such as light color and solution properties. We expect that this magnetic sensing platform holds great promise for various applications in biomedical research and clinical diagnostics.

Systematic pole-zero sorting method for neuro-TF modeling of electromagnetic response.

Neuro-transfer functions (neuro-TF) modeling method has been developed as one of the popular methods for parametric modeling of electromagnetic (EM) filter responses. The discontinuity issue of zero and pole data caused by extraction using vector fitting w.r.t. geometrical parameters change affects the neuro-TF training process and limits its modeling accuracy. This issue is addressed by this paper which proposes a novel systematic pole-zero sorting method for neuro-TF parametric modeling. The proposed method can obtain continuous pole-zero data which change much more smooth w.r.t. geometrical parameters change than the existing neuro-TF method, especially solves the difficulty of disorder of positive and negative values due to small values. The proposed systematic sorting method can substantially improve the modeling accuracy during the establishment and training of neuro-TF model over the existing neuro-TF method without systematic sorting.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

BACKGROUND: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. AIMS: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). METHODS: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. RESULTS: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. DATA ACCESS STATEMENT: Data from this study are available and can be accessed upon request.

Development and validation of a preoperative CT-based risk scoring system for predicting recurrence-free survival in patients undergoing curative surgery for gastric cancer.

PURPOSE: The objective of this study was to establish and validate a preoperative risk scoring system that incorporated both clinical and computed tomography(CT) variables to predict recurrence-free survival (RFS) in gastric cancer(GC) patients who underwent curative resection. METHOD: We retrospectively included consecutive patients with surgically confirmed GC who underwent preoperative CT scans between October 2017 and January 2022. Multivariate Cox regression analysis was employed in the derivation set to identify clinical and CT variables associated with RFS and to construct a risk score. This risk score was subsequently validated in an independent test set. RESULTS: A total of 346 patients were included in the study, with 213 in the derivation set and 133 in the test set. Five variables, namely ctEMVI, ctBorrmann, visceral obesity, sarcopenia, and NLR, were independently associated with RFS. In the test set, the preoperative risk score exhibited a c-index of 0.741, which outperformed the predictive accuracy of pathological tumor staging (c-index of 0.673, p = 0.021) at various time points. The preoperative risk score effectively stratified patients into low and high-risk groups. CONCLUSION: The developed preoperative risk scoring system demonstrated the ability to predict RFS following curative resection in GC patients.