Fine Mapping and Functional Analysis of Major Regulatory Genes of Soluble Solids Content in Wax Gourd (Benincasa hispida)

Soluble solids content (SSC) is an important quality trait of wax gourd, but reports about its regulatory genes are scarce. In this study, the SSC regulatory gene BhSSC2.1 in wax gourd was mined via quantitative trait locus (QTL) mapping based on high-density genetic mapping containing 12 linkage groups (LG) and bulked segregant analysis (BSA)-seq. QTL mapping and BSA-seq revealed for the first time that the SSC QTL (107.658–108.176 cM) of wax gourd was on Chr2 (LG2). The interpretable phenotypic variation rate and maximum LOD were 16.033% and 6.454, respectively. The QTL interval contained 13 genes. Real-time fluorescence quantitative expression analysis, functional annotation, and sequence analysis suggested that Bch02G016960, named BhSSC2.1, was a candidate regulatory gene of the SSC in wax gourd. Functional annotation of this gene showed that it codes for a NADP-dependent malic enzyme. According to BhSSC2.1 sequence variation, an InDel marker was developed for molecular marker-assisted breeding of wax gourd. This study will lay the foundation for future studies regarding breeding and understanding genetic mechanisms of wax gourd.     

Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort

Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST^® ELISA and Lumipulse G^® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815⁻²⁷). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.     

Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1β, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin–antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.     

Insight into crystal growth and upconversion luminescence property of tetragonal Ba3Sc2F12 nanocrystals

Sc-based nanomaterials have attracted consid-erable attention due to their unique optical properties dif-ferent from those of Ln/Y-based nanomaterials.However,s...     

Advances in the Therapeutic Effects of Apoptotic Bodies on Systemic Diseases

Apoptosis plays an important role in development and in the maintenance of homeostasis. Apoptotic bodies (ApoBDs) are specifically generated from apoptotic cells and can contain a large variety of biological molecules, which are of great significance in intercellular communications and the regulation of phagocytes. Emerging evidence in recent years has shown that ApoBDs are essential for maintaining homeostasis, including systemic bone density and immune regulation as well as tissue regeneration. Moreover, studies have revealed the therapeutic effects of ApoBDs on systemic diseases, including cancer, atherosclerosis, diabetes, hepatic fibrosis, and wound healing, which can be used to treat potential targets. This review summarizes current research on the generation, application, and reconstruction of ApoBDs regarding their functions in cellular regulation and on systemic diseases, providing strong evidence and therapeutic strategies for further insights into related diseases.     

复杂产品的层次语义模型研究

针对复杂产品的设计建模提出了一个层次语义模型。在现有三维CAD系统的基础上，从用户需求、产品设计、零件建模、部件装配各个阶段入手，将其中蕴含的行业知识加以分类、提取、抽象，形成设计语义、建模语义和装配语义，使虚拟样机在建立过程中能够利用并且包含更多的行业知识。对该语义模型的三个层次进行了详细讨论，并结合曲柄压力机的产品实例给出了具体实现。     

交变磁处理对金刚石锯片切割性能的影响

选用不同的工艺参数在交变磁场中对金刚石锯片通磁处理,通过对磁处理试件和未磁处理试件的对比切割试验,研究了交变磁处理对金刚石锯片切割性能的影响.研究结果表明:交变磁处理提高了胎体对金刚石的机械把持力,数据统计显示,磁处理锯片金刚石颗粒的脱落率低,参与切割的金刚石数目多,金刚石的有效利用率得到提高;从切割效果来看,交变磁场能够有效提高金刚石锯片的切割性能,但磁处理温度条件对锯片的切割性能有一定的影响;试验优选的磁处理工艺条件为:300 ℃、50 Hz、1 T、60 min,在该工艺条件下,锯片的使用寿命提高46.3%,切割速度提高13.1%;断口组织形貌分析显示,交变磁处理后试件胎体的组织晶粒细小,晶粒细化是金刚石锯片切割性能提高的根本原因.     

Elastic behaviour of polyvinyl chloride melts

A study has been made of the elastic behaviour of Polyvinylchloride commercial samples at high shear stresses, under similar conditions to those used in the processing industry, by means of an extrusion capillary rheometer.The influence in the die swell of variables as molecular weight, temperature and shear rate has been studied. Results are in agreement with general literature data.Smooth extrudates are obtained only in the zone of intermediate shear rates. In this zone it is observed that the die swell increases with shear rate.     

Truly Concomitant and Independently Expressed Short‐ and Long‐Term Plasticity in a Bi2O2Se‐Based Three‐Terminal Memristor

Concomitance of diverse synaptic plasticity across different timescales produces complex cognitive processes. To achieve comparable cognitive complexity in memristive neuromorphic systems, devices that are capable of emulating short‐term (STP) and long‐term plasticity (LTP) concomitantly are essential. In existing memristors, however, STP and LTP can only be induced selectively because of the inability to be decoupled using different loci and mechanisms. In this work, the first demonstration of truly concomitant STP and LTP is reported in a three‐terminal memristor that uses independent physical phenomena to represent each form of plasticity. The emerging layered material Bi₂O₂Se is used for memristors for the first time, opening up the prospects for ultrathin, high‐speed, and low‐power neuromorphic devices. The concerted action of STP and LTP allows full‐range modulation of the transient synaptic efficacy, from depression to facilitation, by stimulus frequency or intensity, providing a versatile device platform for neuromorphic function implementation. A heuristic recurrent neural circuitry model is developed to simulate the intricate “sleep–wake cycle autoregulation” process, in which the concomitance of STP and LTP is posited as a key factor in enabling this neural homeostasis. This work sheds new light on the development of generic memristor platforms for highly dynamic neuromorphic computing.     

Theophylline: Old Drug in a New Light,Application in COVID-19 through Computational Studies

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.