Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants.

BACKGROUND: Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential. METHODS: This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors. RESULTS: During a median follow-up of 14.01 years, 5274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched-chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD. CONCLUSIONS: We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.

Rastonia solanacearum type â ¢ effectors target host 14-3-3 proteins to suppress plant immunity.

14-3-3 proteins play important roles in plant metabolism and stress response. Tomato 14-3-3 proteins, SlTFT4 and SlTFT7, serve as hubs of plant immunity and are targeted by some pathogen effectors. Ralstonia solanacearum with more than 70 type Ⅲ effectors (T3Es) is one of the most destructive plant pathogens. However, little is known on whether R. solanacearum T3Es target SlTFT4 and SlTFT7 and hence interfere with plant immunity. We first detected the associations of SlTFT4/SlTFT7 with R. solanacearum T3Es by luciferase complementation assay, and then confirmed the interactions by yeast two-hybrid approach. We demonstrated that 22 Ralstonia T3Es were associated with both SlTFT4 and SlTFT7, and five among them suppressed the hypersensitive response induced by MAPKKKα, a protein kinase which associated with SlTFT4/SlTFT7. We further demonstrated that suppression of MAPKKKα-induced HR and plant basal defense by the T3E RipAC depend on its association with 14-3-3 proteins. Our findings firstly demonstrate that R. solanacearum T3Es can manipulate plant immunity by targeting 14-3-3 proteins, SlTFT4 and SlTFT7, providing new insights into plant-R. solanacearum interactions.

Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review.

Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC's clinical applications and the profound effects of BCL-2 on cellular apoptosis.

A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid.

Leonurine refers to the desiccated aerial portion of a plant in the Labiatae family. The primary bioactive constituent of Leonurine is an alkaloid, Leonurine alkaloid (Leo), renowned for its substantial therapeutic efficacy in the treatment of gynecological disorders, in addition to its broad-spectrum antineoplastic capabilities. Over recent years, the pharmacodynamic mechanisms of Leo have garnered escalating scholarly interest. Leo exhibits its anticancer potential by means of an array of mechanisms, encompassing the inhibition of neoplastic cell proliferation, induction of both apoptosis and autophagy, and the containment of oncogenic cell invasion and migration. The key signal transduction pathways implicated in these processes include the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), the Phosphoinositide3-Kinase/Serine/Threonine Protein Kinase (PI3K/AKT), the Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase (MAP/ERK). This paper commences with an exploration of the principal oncogenic cellular behaviors influenced by Leo and the associated signal transduction pathways, thereby scrutinizing the mechanisms of Leo in the antineoplastic sequence of events. The intention is to offer theoretical reinforcement for the elucidation of more profound mechanisms underpinning Leo's anticancer potential and correlating pharmaceutical development.

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review.

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body's anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy.

A Soft, High-Density Neuroelectronic Array.

Techniques to study brain activities have evolved dramatically, yet tremendous challenges remain in acquiring high-throughput electrophysiological recordings minimally invasively. Here, we develop an integrated neuroelectronic array that is filamentary, high-density and flexible. Specifically, with a design of single-transistor multiplexing and current sensing, the total 256 neuroelectrodes achieve only a 2.3 × 0.3 mm2 area, unprecedentedly on a flexible substrate. A novel single-transistor multiplexing acquisition circuit further reduces noise from the electrodes, decreased the footprint of each pixel, and potentially increased the device lifetime. The filamentary neuroelectronic array also integrates with a rollable contact pad design, allowing the device to be injected through a syringe, enabling potential minimally invasive array delivery. Successful acute auditory experiments in rats validate the ability of the array to record neural signals with high tone decoding accuracy. Together, these results establish soft, high-density neuroelectronic arrays as promising devices for neuroscience research and clinical applications.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

Objective: To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). Patients and methods: 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). Results: The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). Conclusion: NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.

The relationship between non-suicidal self-injury and childhood abuse in transgender people: a cross-sectional cohort study.

Objective: To explore the relationship between non-suicidal self-injury (NSSI) and childhood abuse in transgender people and the mediating effect of emotional dysregulation traits in the association between childhood abuse and non-suicidal self-injury. Patients and methods: From May to October 2021, 296 female-to-male (FTM) and 675 male-to-females (MTF), with age of 24.5 ± 6.4 years, were recruited using peer-driven sampling and anonymous questionnaires in Guangdong Province. The Childhood Abuse Questionnaire (CTQ-SF), the Personality Diagnostic Questionnaire (PDQ-4+) emotion regulation ability scale and the DSM-5 Clinical Examination of Stereotypic Disorders were used to measure childhood abuse experiences, emotional dysregulation traits and self-injurious behaviour, respectively. Results: Childhood abuse scores were positively correlated with both emotional dysregulation traits scores and non-suicidal self-injury (NSSI) behaviours (p < 0.01), and emotional dysregulation traits scores were positively correlated with NSSI behaviours (p < 0.01); emotional dysregulation traits partially mediated the association between childhood abuse and NSSI behaviours, with the mediating effect accounting for 23.23% of the total effect. In addition, among the factors of childhood abuse, emotional dysregulation traits mediated the association between emotional abuse, emotional neglect, sexual abuse, physical abuse, physical neglect and NSSI behaviour significantly, with the mediating effect accounting for 22.48%-32.58% of the total effect. Conclusion: Transgender NSSI behaviours are associated with childhood abuse and emotional dysregulation traits, and emotional dysregulation traits partially mediates the association between childhood abuse and NSSI behaviours, and screening for emotional dysregulation traits in transgender people and timely interventions are needed to improve the current situation of discrimination against transgender people.

Comprehensive evaluations of a prototype full field-of-view photon counting CT system through phantom studies.

Objective. Photon counting CT (PCCT) has been a research focus in the last two decades. Recent studies and advancements have demonstrated that systems using semiconductor-based photon counting detectors (PCDs) have the potential to provide better contrast, noise and spatial resolution performance compared to conventional scintillator-based systems. With multi-energy threshold detection, PCD can simultaneously provide the photon energy measurement and enable material decomposition for spectral imaging. In this work, we report a performance evaluation of our first CdZnTe-based prototype full-size PCCT system through various phantom imaging studies.Approach.This prototype system supports a 500 mm scan field-of-view and 10 mmz-coverage at isocenter. Phantom scans were acquired using 120 kVp from 50 to 400 mAs to assess the imaging performance on: CT number accuracy, uniformity, noise, spatial resolution, material differentiation and quantification.Main results.Both qualitative and quantitative evaluations show that PCCT, under the tested conditions, has superior imaging performance with lower noise and improved spatial resolution compared to conventional energy integrating detector (EID)-CT. Using projection domain material decomposition approach with multiple energy bin measurements, PCCT virtual monoenergetic images have lower noise, and good accuracy in quantifying iodine and calcium concentrations. These results lead to increased contrast-to-noise ratio (CNR) for both high and low contrast study objects compared to EID-CT at matched dose and spatial resolution. PCCT can also generate super-high resolution images using much smaller detector pixel size than EID-CT and greatly improve image spatial resolution.Significance.Improved spatial resolution and quantification accuracy with reduced image noise of the PCCT images can potentially lead to better diagnosis at reduced radiation dose compared to conventional EID-CT. Increased CNR achieved by PCCT suggests potential reduction in iodine contrast media load, resulting in better patient safety and reduced cost.

Associations of blood cell indices and anemia with risk of incident dementia: A prospective cohort study of 313,448 participants.

INTRODUCTION: Low hemoglobin and anemia are associated with cognitive impairment and Alzheimer's disease (AD). However, the associations of other blood cell indices with incident dementia risk and the underlined mechanisms are unknown. METHODS: Three hundred thirteen thousand four hundred forty-eight participants from the UK Biobank were included. Cox and restricted cubic spline models were used to investigate linear and non-linear longitudinal associations. Mendelian randomization analysis was used to identify causal associations. Linear regression models were used to explore potential mechanisms driven by brain structures. RESULTS: During a mean follow-up of 9.03 years, 6833 participants developed dementia. Eighteen indices were associated with dementia risk regarding erythrocytes, immature erythrocytes, and leukocytes. Anemia was associated with a 56% higher risk of developing dementia. Hemoglobin and red blood cell distribution width were causally associated with AD. Extensive associations exist between most blood cell indices and brain structures. DISCUSSION: These findings consolidated associations between blood cells and dementia. HIGHLIGHT: Anemia was associated with 56% higher risk for all-cause dementia. Hematocrit percentage, mean corpuscular volume, platelet crit, and mean platelet volume had U-shaped associations with incident dementia risk. Hemoglobin (HGB) and red blood cell distribution width had causal effects on Alzheimer's risk. HGB and anemia were associated with brain structure alterations.

Therapeutic efficacy of rare earth carbonate with chemoradiotherapy in late-stage non-small cell lung cancer: a cohort prospective study.

Objective: To compare the therapeutic effects and adverse reactions of sterilizing rare earth carbonate combined with concurrent chemoradiotherapy and simple concurrent chemoradiotherapy in the treatment of late-stage non-small cell lung cancer (NSCLC), and to analyze the reasons for the differences. Method: A total of 817 patients with pathologically diagnosed late-stage NSCLC from June 1, 2021 to December 30, 2022, in the affiliated hospital of Kunming University of Science and Technology, were selected. They were randomly divided into a control group of 394 people and an experimental group of 423 people. The control group was given concurrent chemoradiotherapy (cisplatin + etoposide), while the experimental group simultaneously took a low dose of sterilized rare earth carbonate (0.05mg/Kg). The χ² test and Fisher's test were used to compare the clinical pathological features, objective response rate (ORR), ECOG score, and adverse reactions of the two groups of patients, while survival analysis was used to compare the progression-free survival (PFS) of the two groups. Cox regression analysis was used to test factors related to prognosis. Results: The differences in clinical pathological features between the two groups of patients were not statistically significant, with all P>0.05. The ORR of the control group was 45.18% (178/394), and the experimental group was 89.83% (380/423), with a statistically significant difference (P=0.001). After treatment, the ECOG score of the experimental group was lower than that of the control group, P<0.001. The adverse reaction grading of patients in both groups was below level 3 after treatment, and no treatment-related fatalities occurred. The risk of pulmonary infection and bone marrow suppression in the experimental group was lower than that in the control group. Conclusion: In late-stage NSCLC patients, compared with simple concurrent chemoradiotherapy, the combination of concurrent chemoradiotherapy and sterilizing rare earth carbonate can significantly improve the short-term therapeutic effect and prognosis of patients, with good safety.

Whole genome and transcriptome reveal flavone accumulation in Scutellaria baicalensis roots.

Scutellaria baicalensis Georgi is a medicinal plant in the Lamiaceae family that contains high levels of 4'-deoxyflavone and other flavonoids in its roots. Therefore, it has strong potential as a plant resource for researching the biosynthesis of specific flavonoids. In this study, we report on a chromosome-level S. baicalensis genome assembled to nine chromosomes (376.81M) using PacBio, HiSeq XTen, and Hi-C assisted assembly. The assembly ratio was 99.22%, the contig N50 was 1.80 million bases, and the scaffold N50 was 40.57 million bases, with 31896 genes being annotated. Comparative genome analysis revealed that S. baicalensis and Salvia miltiorrhiza belonged to the same branch, and diverged 36.3 million years ago. Other typically correlated species were Boea hygrometrica and Sesamum indicum. We investigated the structural genes involved in flavonoid synthesis in combination with transcriptome sequencing analysis for different tissues (roots, stems, flowers, leaves) of purple, pink, and white flowers. The results revealed that S.baiF6H is involved in the accumulation of baicalein and was significantly increased in both purple roots vs. pink roots and white roots vs. pink roots. S.baiMYB gene family expression pattern analysis and co-expression network analysis revealed that S.baiMYB transcription factors primarily regulated the production of flavonoids in S. baicalensis. S.baiMYB serves as a major factor regulating flavonoid synthesis in the roots, where yeast one-hybrid assays revealed that these transcription factors could bind to the promoter regions of structural genes to control the accumulation of flavonoids. Genome and transcriptome sequencing, co-expression analysis, and yeast one-hybrid experiments provided valuable genetic resources for understanding flavonoid biosynthesis in S. baicalensis. These findings contribute to a better understanding of the accumulation of metabolites in Lamiaceae.

Big Data Analysis of Manufacturing and Preclinical Studies of Nanodrug-Targeted Delivery Systems: A Literature Review.

Objective: Nanodelivery is a modern technology involving improved delivery methods and drug formulations. The current development and initial applications of nanocarriers are pointing to new directions in the current development of nanomedicine. Researchers are increasingly applying nanodelivery to the delivery of therapeutic or diagnostic agents. This article discusses the preparation and application of nanocomplexes and nanoparticles, as well as their potential future value in clinical research. Through a review and analysis, it is hoped that this will serve as a guide for the future development of various nanodelivery technologies and help researchers learn more about these technologies. Materials and Methods: A literature search was conducted using the keywords "Nano drug delivery" or "Nanomedical materials" or "Nano". A literature search was conducted in three major databases, PubMed, Web of Science, and Google Scholar, using the keywords such as "Nano drug delivery", "Nanomedical materials", or "Nanobubble drug delivery". The initial search was screened by title and abstract. In the full-text review, the titles or abstracts were reviewed according to the selection criteria based on the inclusion criteria. The risk of bias and study quality was assessed according to the Cochrane guidelines, and possible biases such as selection bias and good selection bias were included in the review. Results: A total of 297 studies were included in this study, of which 219 were excluded based on the screening criteria, resulting in the inclusion of 78 studies, the majority of which were original studies and clinical trials, and a small number of which provided design and route of administration analysis of nanomaterial particles and effect fluorograms and were studied in more depth. This paper summarises and reviews the views and directions of the included articles. The main directions include cyclodextrin-based or grafted cyclodextrin nanomaterials, nanobubbles, and stimuli-sensitive and temperature-sensitive nanodelivery systems. Conclusion: The use of innovative, targeted drug delivery systems is effective in cancer drug delivery by summarising the previous studies. However, nanodelivery systems' risks and therapeutic effects need to be evaluated before clinical application. Future research in the field of targeted drug delivery nanosystems should focus on the development of nanocarriers with high in vivo delivery capacity, good synergy with therapeutic agents, and milder short-term and long-term toxicological effects and conduct comprehensive preclinical trials on nanodrug delivery systems with high potential for clinical application as soon as possible, to find nanodrug delivery systems suitable for clinical use and put them into the clinical application as soon as possible.

Serum Cystatin C Level Monitoring for Intervention Opportunity of CBP in Children with Severe Sepsis.

Objective: The aim of this study is to investigate the instruction value of the serum cystatin C (Cys C) level monitoring for intervention opportunity of continuous blood purification technology (CBP) in children with severe sepsis. Methods: 67 children with severe sepsis in the pediatric intensive care unit (PICU) with CBP treatment were retrospectively selected from May 2016 to April 2020. According to the time intervals between the time point of serum Cys C level began to increase (>15 mg/L) and the time point of CBP began, all children were divided into group A (<24 h, 29 cases), group B (24-48 h, 22 cases), and group C (>48 h, 16 cases). The children's general characteristics, vital signs, biochemical parameters, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were evaluated. The influence factors of prognosis of children with severe sepsis were analyzed by multivariate regression analysis. Results: The intervals between the time point of PICU hospitalization and the time point of CBP began and the times of CBP in group A were significantly more than those in group B and C (P < 0.05). There was no statistically significant duration of CBP among three groups (P > 0.05). After follow-up of 28 d, there was no significant difference on the occurrence of coagulation disorders and hypovolemic shock induced by CBP among three groups (P > 0.05). However, the mortality of children in group A was lower than that in group C (P < 0.05). Children in group A had lower APACHE II scores, SOFA scores, serum K+, blood urea nitrogen (BUN), serum creatine (SCr), partial pressure of carbon dioxide (PCO2), and higher partial pressure of oxygen (PO2) than those of children in group C after CBP. (P < 0.05). SOFA scores ≥5 after CBP treatment and the time intervals between the time point of serum Cys C level began to increase (>15 mg/L) and the time point of CBP began ≥24 h were the independent influence factors on the prognosis by multivariate regression analysis. Conclusion: There are significant evidences that continuous blood purification technology within 24 h of serum Cys C level may better control the condition of children with severe sepsis.

Structural characterization and antioxidant activity of Polygonatum sibiricum polysaccharides.

Polysaccharide is one of the main active components of Polygonatum sibiricum. For this study, P. sibiricum polysaccharides (PSP) were obtained through purification using DEAE-Cellulose52 and Sephacryl G-150 column chromatography. The obtained samples were named PSP1, PSP2 and PSP3. The PSP1 sample was found to have the highest content and the best solubility, and a subsequent. So, its structure and characterization were analyzed. The main sugar residue linkages were found to be â†’ 1)-ß-D-Fruf-(2 â†’ 1)-ß-D-Fruf-(2 â†’ 1), 1 â†’ -ß-D-Fruf-(2 â†’ 6)α-D-Glcp (1→, →4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1→ and →6)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1→ link existed. Branch chain analysis indicated →1,6)-ß-D-Fruf-(2→, ß-D-Fruf-(2→, →1,6)-ß-D-Fruf-(2→, →6)-ß-D- Fruf-(2→ link existed, and the link site was at position C-6. In vitro antioxidant activity tests showed that PSP1 had a certain scavenging effect on DPPH, hydroxyl radical, superoxide anion radical and a particular effect on the chelating ability of ferrous. This suggested that P. sibiricum polysaccharides may be a potential antioxidant.

Bilayer-Nanomesh Transparent Neuroelectrodes on 10µm-Thick PDMS.

Transparent electrode arrays have emerged as promising platforms for neural interfacing by enabling simultaneous electrophysiological recording and optical measurements. Soft and thin devices also have compelling advantages due to their less mechanical mismatch with the brain tissue. Here we demonstrate a bilayer-nanomesh-based transparent microelectrode array (MEA) on ultrathin Polydimethylsiloxane (PDMS) substrate. We have successfully fabricated 32-channel, bilayer-nanomesh microelectrodes on PDMS with total device thickness down to only 10µm. In addition to excellent electrode performance, device reliability, and optical transparency, we have also demonstrated successful hydrophilic surface modification and great sterilization compatibility.

Population Dynamics, Effective Soil Factors, and LAMP Detection Systems for Phytophthora Species Associated with Kiwifruit Diseases in China.

China has the largest area of kiwifruit production in the world. Pathogens associated with root diseases of kiwi trees have not been investigated extensively. In this research, three Phytophthora species, Phytophthora cactorum, Phytophthora cinnamomi, and Phytophthora lateralis, which are pathogenic to kiwi trees in the main planting areas of China, were studied. The population densities of these species in 128 soil samples from 32 kiwi orchards in 2017 and 2018 were measured using multiplex real-time quantitative PCR based on the ras-related protein gene Ypt1. P. cactorum was the most widely distributed of the three species in orchards of the Zhouzhi and Meixian prefectures. We used redundancy analysis to examine soil factors in the kiwi orchards to understand their effects on the population densities of the Phytophthora species. The redundancy analysis indicated that soil temperature and pH were significantly correlated with the abundance of P. cactorum and P. cinnamomi. In addition, two loop-mediated isothermal amplification detection systems for P. cactorum were developed based on the tigA gene. The color-change detection system proved to be accurate, sensitive, and faster than quantitative PCR. The results of this study, along with the loop-mediated isothermal amplification detection systems, will be of great use in the control of Phytophthora diseases for the production of kiwifruits in China.

Pentahydroxy flavonoid isolated from Madhuca indica ameliorated adjuvant-induced arthritis via modulation of inflammatory pathways.

Rheumatoid arthritis (RA) is an autoimmune disease associated with advanced joint dysfunction. Madhuca indica J. F. Gmel, from the family Sapotaceae, is an Indian medicinal plant reported to have an array of pharmacological properties. The aim of present investigation was to determine the anti-arthritic potential of an isolated phytoconstituent from methanolic leaf extract of Madhuca indica (MI-ALC) against FCA-induced experimental arthritis. Polyarthritis was induced in female rats (strain: Wistar) via an intradermal injection of FCA (0.1 mL) into the tail. Polyarthritis developed after 32 days of FCA administration. Then rats were treated orally with an isolated phytoconstituent from MI-ALC at doses of 5, 10, and 20 mg/kg. Findings suggested that High-Performance Thin-Layer Chromatography, Fourier-Transform Infrared Spectroscopy, and Liquid Chromatography-Mass Spectrometry spectral analyses of the phytoconstituent isolated from MI-ALC confirmed the structure as 3,5,7,3',4'-Pentahydroxy flavone (i.e., QTN). Treatment with QTN (10 and 20 mg/kg) showed significant (p < 0.05) inhibition of increased joint diameter, paw volume, paw withdrawal threshold, and latency. The elevated synovial oxidative stress (Superoxide dismutase, reduced glutathione, and malondialdehyde) and protein levels of Tumor necrosis factor-α (TNF-α) and Interleukin (ILs) were markedly (p < 0.05) reduced by QTN. It also effectively (p < 0.05) ameliorated cyclooxygenase-2 (COX-2), Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kß) and its inhibitor-α (Ikßα), and ATP-activated P2 purinergic receptors (P2X7) protein expressions as determined by western blot analysis. In conclusion, QTN ameliorates FCA-induced hyperalgesia through modulation of elevated inflammatory release (NF-kß, Ikßα, P2X7, and COX-2), oxido-nitrosative stress, and pro-inflammatory cytokines (ILs and TNF-α) in experimental rats.

Crosstalk in Polymer Microelectrode Arrays.

Thin-film polymer microelectrode arrays (MEAs) facilitate the high-resolution neural recording with its superior mechanical compliance. However, the densely packed electrodes and interconnects along with the ultra-thin polymeric encapsulation/substrate layers give rise to non-negligible crosstalk, which could result in severe interference in the neural signal recording. Due to the lack of standardized characterization or modeling of crosstalk in neural electrode arrays, to date, crosstalk in polymer MEAs remains poorly understood. In this work, the crosstalk between two adjacent polymer microelectrodes is measured experimentally and modeled using equivalent circuits. Importantly, this study demonstrated a two-well measuring platform and systematically characterized the crosstalk in polymer microelectrodes with true isolation of the victim channel and precise control of its grounding condition. A simple, unified equation from detailed circuit modeling was proposed to calculate the crosstalk in different environments. Finite element analysis (FEA) analysis was conducted further to explore the crosstalk in more aggressively scaled polymer electrode threads. In addition to standardizing neural electrode array crosstalk characterization, this study not only reveals the dependence of the crosstalk in polymer MEAs on a variety of key device parameters but also provides general guidelines for the design of thin polymer MEAs for high-quality neural signal recording.