Chinese herbal medicine (CHM) exhibits a broad spectrum of clinical applications and demonstrates favorable therapeutic efficacy. Nonetheless, elucidating the underlying mechanism of action (MOA) of CHM in disease treatment remains a formidable task due to its inherent characteristics of multi-level, multi-linked, and multi-dimensional non-linear synergistic actions. In recent years, the concept of a Quality marker (Q-marker) proposed by Liu et al. has significantly contributed to the monitoring and evaluation of CHM products, thereby fostering the advancement of CHM research. Within this study, a Q-marker screening strategy for CHM formulas has been introduced, particularly emphasising efficacy and biological activities, integrating absorption, distribution, metabolism, and excretion (ADME) studies, systems biology, and experimental verification. As an illustrative case, the Q-marker screening of Qianghuo Shengshi decoction (QHSSD) for treating rheumatoid arthritis (RA) has been conducted. Consequently, from a pool of 159 compounds within QHSSD, five Q-markers exhibiting significant in vitro anti-inflammatory effects have been identified. These Q-markers encompass notopterol, isoliquiritin, imperatorin, cimifugin, and glycyrrhizic acid. Furthermore, by employing an integrated analysis of network pharmacology and metabolomics, several instructive insights into pharmacological mechanisms have been gleaned. This includes the identification of key targets and pathways through which QHSSD exerts its crucial roles in the treatment of RA. Notably, the inhibitory effect of QHSSD on AKT1 and MAPK3 activation has been validated through western blot analysis, underscoring its potential to mitigate RA-related inflammatory responses. In summary, this research demonstrates the proposed strategy's feasibility and provides a practical reference model for the systematic investigation of CHM formulas.
The effect of melatonin treatment on the carotenoid metabolism in broccoli florets during storage was explored. The results indicated that 100 µmol/L of melatonin maintained the sensory quality of broccoli florets, which retarded the increase of the L* value and the decrease of the H value. Melatonin treatment increased the activities of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acetyltransferase (SNAT) and N-acetylserotonin methyltransferase (ASMT), leading to the enrichment of endogenous melatonin content in broccoli florets. Meanwhile, the treatment inhibited the concentrations of β-carotene, β-cryptoxanthin, zeaxanthin and lutein, which was beneficial in delaying the yellowing of broccoli. In addition, a series of carotenoid biosynthetic genes such as BoPSY, BoPDS, BoZDS, BoLCYβ and BoZEP was also suppressed by melatonin. Further analysis revealed that the lower carotenoid content and the down-regulated BoNCED expression in treated broccoli resulted in less accumulation of abscisic acid precursors, inhibiting abscisic acid production during the yellowing process.
The effect of fructose on γ-aminobutyric acid (GABA) content and its metabolic pathway in broccoli sprouts was investigated. The results demonstrated that the fructose treatment not only significantly increased the fresh weight, GABA, and glutamate contents in sprouts, but also promoted the activity of glutamic acid decarboxylase (GAD) and the expressions of BoGAD1 and BoGAD2. Meanwhile, fructose treatment inhibited the stem length of broccoli sprouts and enhanced the abscisic acid (ABA) production in comparison with the control. Ca2+, CaM contents, and BoCaM2 expression in broccoli sprouts were also stimulated after fructose treatment. Exogenous fructose increased inositol trisphosphate (IP3) content and activated the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) and the expression of BoPLC2, contributing to Ca2+ influx into the cells. These results suggested that Ca2+ played an essential role in GABA enrichment under fructose treatment, which may be associated with GAD and PI-PLC.
It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.
17β-Estradiol-E2 (17β-E2) is a steroid hormone that plays a major role in the reproductive endocrine system and is involved in various processes, such as pregnancy, fertility, and menopause. In this study, the performance of an enzyme-linked immunosorbent assay (ELISA) for 17β-E2 quantification was enhanced by using a gold nanoparticle (GNP)-conjugated aptamer. An anti-17β-E2-aptamer-GNP antibody was immobilized on an amine-modified ELISA surface. Then, 17β-E2 was allowed to interact with and be sandwiched by antibodies. Aptamer-GNP conjugation was confirmed by colorimetric assays via the naked eye and UV-visible light spectroscopy. The detection limit based on a signal-to-noise ratio (S/N) of 3 was estimated to be 1.5 nM (400 pg/mL), and the linear range was 1.5-50 nM. Control experiments (without 17β-E2/with a complementary aptamer sequence/with a nonimmune antibody) confirmed the specific detection of 17β-E2. Moreover, 17β-E2 spiking of human serum did not interrupt the interaction between 17β-E2 and its antibody and aptamer. Thus, the developed ELISA can be used as an alternate assay for quantification of 17β-E2 and assessment of endocrine-related gynecological problems.
The aim of this study was to assess the inhibitory effects of Sonchus olearleu extract on the generation of heterocyclic amines in roasted pork patties cooked by pan-frying. All samples were cooked for two different durations (45 min and 105 min) under 200 °C and 230 °C. 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-ami- no-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinox-aline (4,8-DiMeIQx), harman, and norharman were detected and quantified. In patties cooked at 230 °C for 105 min, S. olearleu extract (0.5%) significantly inhibited the formation of IQ, harman, and norharman by 39%, 67%, and 63%, respectively. In contrast to IQ, the levels of harman and norharman were significantly reduced by the extracts tested. However, no such effects were observed for MeIQx and 4, 8-DiMeIQx. Notably, the inhibitory effect on heterocyclic amines is significantly correlated with the antioxidant potential and total phenolic content of S. olearleu extract.
Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.
Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed.
A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 5.0[Formula: see text] collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25[Formula: see text] respectively, in the pseudorapidity range [Formula: see text], [Formula: see text] and with an angular separation [Formula: see text], is [Formula: see text][Formula: see text]. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.
A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
The effective solution to avoid machinery damage caused by resonance has been perplexing the field of engineering as a core research direction since the resonance phenomenon was discovered by Euler in 1750. Numerous attempts have been performed to reduce the influence of resonance since the earlier of last century, by introducing a nonlinear structure or a closed-loop control system. However, the existed methodologies cannot eliminate resonance completely even extra problems were introduced inevitably, which means the technical choke-point of resonance-free remains unsolved. Here we propose a designable archetype model, which establishes a mapping between the mechanical properties and its structure. A general inverse method for structure construction is proposed based upon the required property for the system with quasi-zero stiffness of any designed finite order and the zero-stiffness properties. It is shown that an ellipse trajectory tracking of the designed model is the sufficient and necessary condition to satisfy the zero-stiffness property. Theoretical analysis shows that no resonant response happens in a zero-stiffness system to the full-band frequency excitation, or equivalently, the system can completely isolate the energy transfer between the load and environment, when the damping ratio approaches zero. Finally, an experimental rig for the prototype structure is built up according to the sufficient and necessary condition of the zero-stiffness system, for which the special dynamic behaviours are verified through experiments of frequency-sweep and random-vibration as well. Experimental results show that the prototype of the initial vibration isolation frequency of zero-stiffness system is much lower than 0.37 Hz, and the vibration attenuation of the proposed model is about 16.86 dB, 45.63 dB, and 112.37 dB at frequencies of 0.37 Hz, 1 Hz, and 10 Hz, respectively. The distinguished geometric structure of the zero-stiffness system leads to a new inspiration for the design of resonance-free in metamaterial unit and the inverse method can even adapt the design for a more targeted applications based on an arbitrary complex dynamic requirement.
The basic mechanism of reinforcement in tendons addresses the transfer of stress, generated by the deforming proteoglycan (PG)-rich matrix, to the collagen fibrils. Regulating this mechanism involves the interactions of PGs on the fibril with those in the surrounding matrix and between PGs on adjacent fibrils. This understanding is key to establishing new insights on the biomechanics of tendon in various research domains. However, the experimental designs in many studies often involved long sample preparation time. To minimise biological degradation the tendons are usually stored by freezing. Here, we have investigated the effects of commonly used frozen storage temperatures on the mechanical properties of tendons from the tail of a murine model (C57BL6 mouse). Fresh (unfrozen) and thawed samples, frozen at temperatures of -20°C and -80°C, respectively, were stretched to rupture. Freezing at -20°C revealed no effect on the maximum stress (σ), stiffness (E), the corresponding strain (ε) at σ and strain energy densities up to ε (u) and from ε until complete rupture (up). On the other hand, freezing at -80°C led to higher σ, E and u; ε and up were unaffected. The results implicate changes in the long-range order of radially packed collagen molecules in fibrils, resulting in fibril rupture at higher stresses, and changes to the composition of extrafibrillar matrix, resulting in an increase in the interaction energy between fibrils via collagen-bound PGs.
Cervical, ovarian, and endometrial cancers are common in the female reproductive system. Cervical cancer starts from the cervix, while ovarian cancer develops when abnormal cells grow in the ovary. Endometrial or uterine cancer starts from the lining of the womb in the endometrium. Approximately 12,000 women are affected every year by cervical cancer in the United States. Squamous cell carcinoma antigen (SCC-Ag) is a well-established biomarker in serum for diagnosing gynecological cancers, and its levels were observed to be elevated in cervical, ovarian, and endometrial cancer patients. Moreover, SCC-Ag was used to identify the tumor size and progression stages. Various biosensing systems have been proposed to identify SCC-Ag; herein, enhanced interdigitated electrode sensing is presented with the use of gold nanoparticles (GNPs) to conjugate an antigen/antibody. It was proved that the limit of detection is 62.5 fM in the case of antibody-GNP, which is 2-fold higher than that by SCC-Ag-GNP. Furthermore, the antibody-GNP-modified surface displays greater current increases with concomitant dose-dependent SCC-Ag levels. High analytical performance was shown by the discrimination against α-fetoprotein and CYFRA 21-1 at 1 pM. An enhanced sensing system is established for gynecological tumors, representing an advance from the earlier detection methods.
Stutzerimonas stutzeri is an opportunistic pathogenic bacterium belonging to the Gammaproteobacteria, exhibiting wide distribution in the environment and playing significant ecological roles such as nitrogen fixation or pollutant degradation. Despite its ecological importance, only two S. stutzeri phages have been isolated to date. Here, a novel S. stutzeri phage, vB_PstS_ZQG1, was isolated from the surface seawater of Qingdao, China. Transmission electron microscopy analysis indicates that vB_PstS_ZQG1 has a morphology characterized by a long non-contractile tail. The genomic sequence of vB_PstS_ZQG1 contains a linear, double-strand 61,790-bp with the G+C content of 53.24% and encodes 90 putative open reading frames. Two auxiliary metabolic genes encoding TolA protein and nucleotide pyrophosphohydrolase were identified, which are likely involved in host adaptation and phage reproduction. Phylogenetic and comparative genomic analyses demonstrated that vB_PstS_ZQG1 exhibits low similarity with previously isolated phages or uncultured viruses (average nucleotide identity values range from 21.7 to 29.4), suggesting that it represents a novel viral genus by itself, here named as Fuevirus. Biogeographic analysis showed that vB_PstS_ZQG1 was only detected in epipelagic and mesopelagic zone with low abundance. In summary, our findings of the phage vB_PstS_ZQG1 will provide helpful insights for further research on the interactions between S. stutzeri phages and their hosts, and contribute to discovering unknown viral sequences in the metagenomic database.
Stutzerimonas stutzeri is an opportunistic pathogen widely distributed in the environment and displays diverse metabolic capabilities. In this study, a novel lytic S. stutzeri phage, named vB_PstM_ZRG1, was isolated from the seawater in the East China Sea (29°09'N, 123°39'E). vB_PstM_ZRG1 was stable at temperatures ranging from -20°C to 65°C and across a wide range of pH values from 3 to 10. The genome of vB_PstM_ZRG1 was determined to be a double-stranded DNA with a genome size of 52,767 bp, containing 78 putative open reading frames (ORFs). Three auxiliary metabolic genes encoded by phage vB_PstM_ZRG1 were predicted, including Toll/interleukin-1 receptor (TIR) domain, proline-alanine-alanine-arginine (PAAR) protein and SGNH (Ser-Gly-Asn-His) family hydrolase, especially TIR domain is not common in isolated phages. Phylogenic and network analysis showed that vB_PstM_ZRG1 has low similarity to other phage genomes in the GenBank and IMG/VR database, and might represent a novel viral genus, named Elithevirus. Additionally, the distribution map results indicated that vB_PstM_ZRG1 could infect both extreme colds- and warm-type hosts in the marine environment. In summary, our finding provided basic information for further research on the relationship between S. stutzeri and their phages, and expanded our understanding of genomic characteristics, phylogenetic diversity and distribution of Elithevirus.
For a long time, how anti-inflammatory factors evolved was largely unknown. In this study, we chose a marine invertebrate, Litopenaeus vannamei, as a model and identified that shrimp mesencephalic astrocyte-derived neurotrophic factor (MANF) was an LPS-induced plasma protein, which exerted its anti-inflammatory roles on shrimp hemocytes by suppressing ERK phosphorylation and Dorsal expression. In addition, we demonstrated that shrimp MANF could be associated with a receptor protein tyrosine phosphatase (RPTP) to mediate negative regulation of ERK activation and Dorsal expression. More interestingly, shrimp RPTP-S overexpression in 293T cells could switch shrimp and human MANF-mediated ERK pathway activation to inhibition. In general, our results indicate that this conserved RPTP is the key component for extracellular MANF-mediated ERK pathway inhibition, which gives a possible explanation about why this neurotropic factor could both protect neuron cells from apoptosis and inhibit immune cell M1 activation in various species.
Despite the importance of innate immunity in invertebrates, the diversity and function of innate immune cells in invertebrates are largely unknown. Using single-cell RNA-seq, we identified prohemocytes, monocytic hemocytes, and granulocytes as the three major cell-types in the white shrimp hemolymph. Our results identified a novel macrophage-like subset called monocytic hemocytes 2 (MH2) defined by the expression of certain marker genes, including Nlrp3 and Casp1. This subtype of shrimp hemocytes is phagocytic and expresses markers that indicate some conservation with mammalian macrophages. Combined, our work resolves the heterogenicity of hemocytes in a very economically important aquatic species and identifies a novel innate immune cell subset that is likely a critical player in the immune responses of shrimp to threatening infectious diseases affecting this industry.
Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.