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Frailty is an age-related condition characterized by a decline in physical capacity with an increased vulnerability to stressors. During the COVID-19 pandemic, there was considerable progression in frailty in older adults. Therefore, an online frailty check (FC) is required for continuous screening, especially acceptable to older adults. We aimed to co-design/co-develop an online FC application with FC supporters who were facilitators in a pre-existing onsite FC program in the community. It consisted of a self-assessment of sarcopenia and an 11-item questionnaire assessing dietary, physical, and social behaviors. Opinions obtained from FC supporters (median 74.0 years) were categorized and implemented. The usability was assessed using the system usability scale (SUS). For both FC supporters and participants (n = 43), the mean score was 70.2 ± 10.3 points, which implied a “marginally high” acceptability and a “good” adjective range. Multiple regression analysis showed that the SUS score was significantly correlated with onsite–online reliability, even after adjusting for age, sex, education level, and ICT proficiency (b = 0.400, 95% CI: 0.243–1.951, p = 0.013). We also validated the online FC score, which showed a significant association between onsite and online FC scores (R = 0.670, p = 0.001). In conclusion, the online FC application is an acceptable and reliable tool to check frailty for community-dwelling older adults.

Background Metrnl is a new kind of adipokine, which is also known as meteorin-like because it is homologous to the neurotrophic factor meteorin (Metrn). Although the expression and function of Metrnl, including neurotrophic, immunomodulatory, and insulin resistance functions in different tissues, have been extensively studied, research on its role in sepsis has remained largely limited.Methods The present work analyzed the levels of Metrnl and cytokines in the circulation, such as tumor necrosis factor (TNF-α), interleukin (IL-1)β, IL-6, IL-8, together with IL-10 among septic adult patients. Clinical information was obtained from such patients, including sofa score, procalcitonin(PCT)count, and C-reactive count (CRP) at the time of entering the intensive care unit (ICU). We constructed a sepsis model in Metrnl-deficient or normal wild-type mice using cecal ligation and perforation to study its functions in bacterial burden, survival, cytokine/chemokine generation, peritoneal lavage fluid neutrophils, macrophage and lymphocyte recruitment, and Treg/Th17 immune cell balance after CLP-induced sepsis.Results The expression of Metrnl was remarkably elevated in the early phase of sepsis clinically. Its serum content in patients dying of sepsis slightly decreased relative to that in survivors. Furthermore, the concentration of Metrnl in septic cases when entering the ICU independently predicted the 28-day mortality. For septic patients who had low serum Metrnl content (≤ 359.40 pg/mL), the death risk increased by 2.3 folds relative to those who had a high serum content. It is reported that Metrnl is probably insufficient among patients dying of sepsis. Additionally, the content of Metrnl in the serum of septic patients when entering the ICU is markedly and negatively related to the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17, PCT, and Sofa score. Collectively, Metrnl could be a potential therapeutic target for sepsis. A low-lethality non-severe sepsis (NSS) model was constructed, which suggested that Metrnl insufficiency elevated the death rate and reduced bacterial clearance during sepsis. For Metrnl-deficient mice, impaired sepsis immunity defense might be related to decreased macrophage recruitment and Treg/Th17 lymphocyte imbalance. Recombinant Metrnl administered to Metrnl-deficient mice abolished the immunity defense impairment following NSS while protecting the high-lethality severe sepsis (SS) model in wild-type (WT) mice. In addition, Metrnl-induced sepsis prevention was intricately associated with the increased recruitment of peritoneal macrophages and modulation of the Treg/TH17 immune cell balance. Furthermore, CCL3 exposure in Metrnl-deficient mice reduced peritoneal bacterial loads while improving survival during sepsis partially by promoting the recruitment of peritoneal macrophages. Furthermore, Metrnl regulated the polarization of M1 macrophages through the ROS signaling pathway and promoted macrophage phagocytosis, thereby killing Escherichia coli.Conclusions The present proof-of-concept work suggests that Metrnl-mediated recruitment of macrophages significantly affects sepsis defense in the host and modulates the Treg/Th17 immune cell balance. Findings in this work shed more light on the development of host-directed treatments that can be used to manipulate host immunity to treat sepsis.

Telomere to telomere (T2T) assembly relies on the correctness of sequence alignments. However, the existing aligners tend to generate a high proportion of false-positive alignments in repetitive genomic regions which impedes the generation of T2T-level reference genomes for more important species. In this paper, we present an automatic algorithm called RAfilter for removing the false-positives in the outputs of existing aligners. RAfilter takes advantage of rare k-mers representing the copy-specific features to differentiate false-positive alignments from the correct ones. Considering the huge numbers of rare k-mers in large eukaryotic genomes, a series of high-performance computing techniques such as multi-threading and bit operation are used to improve the time and space efficiencies. The experimental results on tandem repeats and interspersed repeats show that RAfilter was able to filter 60%–90% false-positive HiFi alignments with almost no correct ones removed, while the sensitivities and precisions on ONT datasets were about 80% and 50% respectively.

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) has been demonstrated to be a promising target for treating inflammatory diseases. Herein, we describe the discovery and optimization of a series of RIPK2 inhibitors derived from an FLT3 inhibitor, CHMFL-FLT3-165. Compound

This paper presents the effects of matrix and interface on the fracture toughness and progressive damage mechanisms of 2.5D woven SiCf/SiC composites. Third-generation SiC fibers were selected. 2.5D woven SiCf/SiC composites with four interfacial layers PyC, PyC/SiC, BN, BN/SiC and two matrix polycarbosilane (PCS) and liquid hyperbranched polycarbosilane with vinyl groups (VHPCS) were prepared by a combination of chemical vapour deposition (CVD), chemical vapor infiltration (CVI), and precursor infiltration pyrolysis (PIP) processes, respectively. Single edge notch bending (SENB) tests were carried out to investigate the fracture toughness. Moreover, acoustic emission (AE) and X-ray micro-computed tomography (Micro-CT) techniques were employed to analyze the progressive mechanical properties and failure mechanism. Results showed that the matrix and interface have significant effects on the fracture toughness. Moreover, 2.5D woven composites with PyC/SiC interfacial layers and VHPCS matrix have the highest fracture toughness (16.93 ± 1.20 Mpa • m1/2). Furthermore, during progressive damage, the pores can influence the crack expansion path, and effectively regulate the stress concentration and increase the toughness of the composites.

Pan-genomes from large natural populations can capture genetic diversity and reveal genomic complexity. Using de novo long-read assembly, we generated a graph-based super pan-genome of rice consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. Our pan-genome reveals extensive structural variations (SVs) and gene presence/absence variations. Additionally, our pan-genome enables the accurate identification of nucleotide-binding leucine-rich repeat genes and characterization of their inter- and intraspecific diversity. Moreover, we uncovered grain weight-associated SVs which specify traits by affecting the expression of their nearby genes. We characterized genetic variants associated with submergence tolerance, seed shattering and plant architecture and found independent selection for a common set of genes that drove adaptation and domestication in Asian and African rice. This super pan-genome facilitates pinpointing of lineage-specific haplotypes for trait-associated genes and provides insights into the evolutionary events that have shaped the genomic architecture of various rice species.

To identify abnormal functional connectivity of the default mode network in cingulate gyrus epilepsy, which may yield new information about the default mode network and suggest a new cingulate gyrus epilepsy biomarker. Fifteen patients with cingulate gyrus epilepsy (mean age = 21 years) and 15 healthy controls (mean age = 24 years) were studied in the resting state using magnetoencephalography. Twelve brain areas of interest in the default mode network were extracted and investigated with multifrequency signals that included alpha (α, 8–13 Hz), beta (β, 14–30 Hz), and gamma (γ, 31–80 Hz) band oscillations. Patients with cingulate gyrus epilepsy had significantly greater connectivity in all three frequency bands (α, β, γ). A frequency‐specific elevation of functional connectivity was found in patients compared to controls. The greater functional connectivity in the γ band was significantly more prominent than that of the α and β bands. Patients with cingulate gyrus epilepsy and controls differed significantly in functional connectivity between the left angular gyrus and left posterior cingulate cortex in the α, β, and γ bands. The results of the node degree analysis were similar to those of the functional connectivity analysis. Our findings reveal for the first time that brain activity in the γ band may play a key role in the default mode network in cingulate gyrus epilepsy. Altered functional connectivity of the left angular gyrus and left posterior cingulate cortex may be a new biomarker for cingulate gyrus epilepsy.

With the increasing incidence of antibiotic resistance, there is an urgent need to develop new antibiotics with excellent activity against drug-resistant bacteria. Three novel series of tylosin semisynthetic derivatives were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. Among these derivatives, compound C-2 demonstrated potent antibacterial activity against both gram-positive and gram negative bacteria, and non mutagenic. More importantly, compound C-2 displayed high antimicrobial potency against Gram-positive bacteria in a murine model, and was found to be more efficient than tildipirosin. Thus, compound C-2 had great potential as a promising lead compound for the treatment of bacterial infection.

In this study, a novel batch of indazole containing 1,2,3-triazole agents were designed and synthesized. The antiproliferative activity of target compounds in four human cancer cells, PC-3 (human prostate cancer cell), MCF-7 (human breast cancer cell), HepG-2 (human hepatoma cell) and MGC-803 (human gastric cancer cell), was evaluated by thiazole blue (MTT). In the antiproliferative activity screening, we were surprised to find that most compounds have specific cytotoxicity to PC-3 cancer cells. In particular, 9a has an IC

Sequence alignment is the basis of gene functional annotation for unknow sequences. Selecting closely related species as the reference species should be an effective way to improve the accuracy of gene annotation for plants, compared with only based on one or some model plants. Therefore, limited species number in previous software or website is disadvantageous for plant gene annotation.Here, we collected the protein sequences of 236 plant species with known genomic information from 63 families. After that, these sequences were annotated by pfam, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to construct our databases. Furthermore, we developed the software, Gene Annotation Software for Plants (GFAP), to perform gene annotation using our databases. GFAP, an open-source software running on Windows and MacOS systems, is an efficient and network independent tool. GFAP can search the protein domain, GO and KEGG information for 43000 genes within 4 minutes. In addition, GFAP can also perform the sequence alignment, statistical analysis and drawing. The website of https://gitee.com/simon198912167815/gfap-database provides the software, databases, testing data and video tutorials for users.GFAP contained large amount of plant-species information. We believe that it will become a powerful tool in gene annotation using closely related species for phytologists.

Objective. Repetitive transcranial magnetic stimulation (rTMS) emerges as a useful therapy for autism spectrum disorder (ASD) clinically. Whereas the mechanisms of action of rTMS on ASD are not fully understood, and no biomarkers until now are available to reliably predict the follow-up rTMS efficacy in clinical practice. Approach. In the current work, the temporal variability was investigated in resting-state electroencephalogram of ASD patients, and the nonlinear complexity of related time-varying networks was accordingly evaluated by fuzzy entropy. Main results. The results showed the hyper-variability in the resting-state networks of ASD patients, while three week rTMS treatment alleviates the hyper fluctuations occurring in the frontal-parietal and frontal-occipital connectivity and further contributes to the ameliorative ASD symptoms. In addition, the changes in variability network properties are closely correlated with clinical scores, which further serve as potential predictors to reliably track the long-term rTMS efficacy for ASD. Significance. The findings consistently demonstrated that the temporal variability of time-varying networks of ASD patients could be modulated by rTMS, and related variability properties also help predict follow-up rTMS efficacy, which provides the potential for formulating individualized treatment strategies for ASD (ChiCTR2000033586).

A novel fusion algorithm based on guided filter (GF) for computed tomography (CT) and magnetic resonance imaging (MRI) medical images is proposed. In this algorithm: approximation coefficient and three wavelet coefficients of CT and MRI are obtained by the wavelet transform, respectively. Two weight maps are obtained by comparison of the pixel values of the two approximation coefficients. A GF is designed with the weight maps serving as the input image and the corresponding approximation coefficient serving as the guided image; the GF is used to smooth the weight images and refined weight maps are obtained. The approximation and wavelet coefficients of CT and MRI images are fused by the weighted fusion algorithm with refined weight maps. A fused image of CT and MRI is obtained by the inverse wavelet transform. Comparisons of this algorithm with two fusion algorithms available show that the fused image based on this algorithm contains a greater amount of information, more details and clearer edges than the other two algorithms. Therefore, this algorithm is better at locating the position and shape of the target volume. In the course of treatment, this algorithm can better avoid the surrounding health organs by radiation, protect the health of patients.

Plant γ-glutamylcysteine ligase (GCL), catalyzing the first and tightly regulated step of glutathione (GSH) biosynthesis, is redox-activated via formation of an intramolecular disulfide bond. In vitro, redox-activation of recombinant GCL protein causes formation of homo-dimers. Here, we have investigated whether dimerization occurs in vivo and if so whether it contributes to redox-activation. FPLC analysis indicated that recombinant redox-activated WT (wild type) AtGCL dissociates into monomers at concentrations below 10−6 M, i.e. below the endogenous AtGCL concentration in plastids, which was estimated to be in the micromolar range. Thus, dimerization of redox-activated GCL is expected to occur in vivo. To determine the possible impact of dimerization on redox-activation, AtGCL mutants were generated in which salt bridges or hydrophobic interactions at the dimer interface were interrupted. WT AtGCL and mutant proteins were analyzed by non-reducing SDS–PAGE to address their redox state and probed by FPLC for dimerization status. Furthermore, their substrate kinetics (KM, Vmax) were compared. The results indicate that dimer formation is not required for redox-mediated enzyme activation. Also, crystal structure analysis confirmed that dimer formation does not affect binding of GSH as competitive inhibitor. Whether dimerization affects other enzyme properties, e.g. GCL stability in vivo, remains to be investigated.

The rate of social participation of senior citizens in a senior club’s activities is not equal to the rate of desire for the said participation. Earlier studies mainly examined personal and social factors which influence the participation rate, overlooking the practical methods by which senior citizens can overcome barriers to participating in club activities. Our study aims to clarify the features of a club activity as a resource by analyzing the activity’s interactions. Our study is based on data extracted from videotaped recordings of a senior calligraphy club in Kanto, Japan. In September 2018, one lecturer and 11 participants were videotaped for 3 hours, and the video underwent conversation analysis, which elucidates how people organize activities under specific circumstances. We analyzed how a female newcomer to the activity initiated face-to-face interaction, which is considered the first step of social participation. She talked to other participants who were familiar with the exercise several times by inquiring how to read kanjis on teaching materials. These findings suggest that visualization of skill relative to the other creates an environment for initiating face-to-face interaction. In this case, the newcomer utilized the difference in skill denoted by teaching materials and was given the rational reason to talk to the others already engaging in the activity. Therefore, designing teaching materials that assign the learning level of each participant may be effective in promoting social participation in senior study clubs.

The increase of vegetable planting area lead to the large amounts of VPW (vegetable processing wastes). Effects of V% (VPW proportion) and I% (inoculum proportion) on water free anaerobic co-digestion of VPW with CS (cattle slurry) for methane production was investigated. The results showed that the total methane production was increased from 141.2 L/kg VS (volatile solids) to 186.8 L/kg VS with V% increasing from 17% to 35%. When V%, I% and TS% (total solids content) were 35%, 40% and 7.9%, respectively, the maximal methane production of 186.8 L/kg VS was obtained. However, the optimal conditions were 35% of V% and 30% of I%, the methane production was 170.8 L/kg VS, the maximal methane production was only 9.4% higher than that of the optimal conditions, the TS% of the optimal condition was 8.6% and higher than that of the maximal methane production, the reductions of TS% and VS% for this condition were 29.5% and 49.2%, respectively, and the T 80 for this condition was 42.9% shorter than that of the maximal methane production. The results indicate VPW can be co-digested with CS without water addition.

Yingxue Yang,1,2 Xiating Zhang,1,2 Yu Zhu,1,2 Yakang Dai,3 Ting Liu,3 Yuping Wang1,2 1Department of Neurology, Xuanwu Hospital, Capital Medical University, 2Beijing Key Laboratory of Neuromodulation, Beijing, People’s Republic of China; 3Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, People’s Republic of China Background: Cognitive function in anxiety disorders has been the subject of limited investigation, especially in generalized anxiety disorder (GAD). The purpose of this study was to investigate the cognitive function in subjects with GAD using mismatch-triggered negativity N270.Methods: Fifteen medication-free patients with a DSM-IV diagnosis of GAD, and 15 well-matched healthy controls performed a dual-feature delayed matching task while event-related potentials were recorded from their scalp.Results: The GAD group was characterized by the decreased N270 amplitude in the left hemisphere. The smaller N270 amplitude was associated with greater symptoms of anxiety and depression.Conclusion: Since N270 is thought to index cognitive function in different domains, including attention and memory, our results suggest that individuals with GAD have an impaired cognitive function, particularly in selective attention and working memory. These cognitive deficits may have clinical significance in subjects with GAD and should be considered in treatment planning. Keywords: generalized anxiety disorder, N270, cognitive function, selective attention, working memory

Until recently, paroxysmal hypnogenic dyskinesia was thought to be a rare movement disorder characterized by intermittent dystonia and/or choreoathetoid movements that occur during non-rapid eye movement sleep, with consciousness preserved once the patient is awakened during the episodes. Recent investigations have revealed that most, but not all, paroxysmal hypnogenic dyskinesia cases are actually frontal lobe epilepsy. Here, we present two cases with paroxysmal choreoathetoid movements on waking during non-rapid eye movement sleep. Although they did not respond to antiepileptic drugs, they did respond to antidopaminergic drugs. This supports the opinion that non-epileptic paroxysmal hypnogenic dyskinesia does exist.

Background & Aims Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear. Methods We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured. Results The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p

Background Solid-state anaerobic digestion (SS-AD) was initially adopted for the treatment of municipal solid waste. Recently, SS-AD has been increasingly applied to treat lignocellulosic biomass, such as agricultural and forestry residues. However, studies on the SS-AD process are few. In this study, the process performance and methane yield from SS-AD of alkaline-pretreated poplar processing residues (PPRs) were investigated using the properties of soil, such as buffering capacity and nutritional requirements. Results The results showed that the lignocellulosic structures of the poplar sample were effectively changed by NaOH pretreatment, as indicated by scanning electron microscopy and Fourier transform infrared spectra analysis. The start-up was markedly hastened, and the process stability was enhanced. After NaOH pretreatment, the maximum methane yield (96.1 L/kg volatile solids (VS)) was obtained under a poplar processing residues-to-soil sample (P-to-S) ratio of 2.5:1, which was 29.9% and 36.1% higher than that of PPRs (74.0 L/kg VS) and that of experiments without NaOH pretreatment (70.6 L/kg VS), respectively. During steady state, the increase in the methane content of the experiment with a P-to-S ratio of 2.5:1 was 4.4 to 50.9% higher than that of the PPRs. Degradation of total solids and volatile solids ranged from 19.3 to 33.0% and from 34.9 to 45.9%, respectively. The maximum reductions of cellulose and hemicellulose were 52.6% and 42.9%, respectively, which were in accordance with the maximal methane yield. T80 for the maximum methane yield for the experiments with NaOH pretreatment was 11.1% shorter than that for the PPRs. Conclusions Pretreatment with NaOH and addition of soil led to a significant improvement in the process performance and the methane yield of SS-AD of PPRs. The changes in lignocellulosic structures induced by NaOH pretreatment led to an increase in methane yield. For the purpose of practical applications, SS-AD with soil addition is a convenient, economical, and practical technique.