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Single-cell approaches have become an increasingly popular way of understanding the genetic factors behind disease. Isolation of DNA and RNA from human tissues is necessary to analyze multi-omic data sets, providing information on the single-cell genome, transcriptome, and epigenome. Here, we isolated high-quality single-nuclei from postmortem human heart tissues for DNA and RNA analysis. Postmortem human tissues were obtained from 106 individuals, 33 with a history of myocardial disease, diabetes, or smoking, and 73 controls without heart disease. We demonstrated that the Qiagen EZ1 instrument and kit consistently isolated genomic DNA of high yield, which can be used for checking DNA quality before conducting single-cell experiments. Here, we provide a method for single-nuclei isolation from cardiac tissue, otherwise known as the SoNIC method, which allows for the isolation of single cardiomyocyte nuclei from postmortem tissue by nuclear ploidy status. We also provide a detailed quality control measure for single-nuclei whole genome amplification and a pre-amplification method for confirming genomic integrity.

The epoxidation reaction over titanium silicalite-1 (TS-1) zeolites is a green way to produce epoxides that are important intermediates for chemicals. Nevertheless, the conventional microporous TS-1 zeolite shows limited diffusion ability for bulky molecules, leading to poor activity and low selectivity. Constructing hierarchical porosity in microporous materials is an effective strategy to enhance the diffusion properties of catalysts. However, there are few reports on the design and synthesis of TS-1 zeolites with hierarchical structure featuring multilevels, interconnectivity, and regularity for efficient diffusion and epoxidations. Herein, hierarchical TS-1 zeolites with ordered macro-meso-microporosity (OMMM-TS-1) are obtained by a method combining a templated effect of ordered macro-mesoporous matrices and a confined in situ crystallization process. The OMMM-TS-1 possesses ordered macropores with tunable size (∼200-600 nm), ordered mesopores (∼8 nm), and intact micropores (∼0.5 nm). The OMMM-TS-1 achieves a cyclooctene conversion as 3.6 times and 1.8 times and a selectivity to epoxy product as 1.6 times and 1.3 times higher than the conventional TS-1 (C-TS-1) and nanosized TS-1 (Nano-TS-1) zeolites, respectively. The OMMM-TS-1 also outperforms the C-TS-1 and Nano-TS-1 zeolites in epoxidations of a series of alkenes. Such a novel hierarchical structure can be applied in the design and synthesis of many other catalysts.

This study explores the strategic issues related to the mobile learning quality in Taiwanese higher education during the COVID-19 pandemics. While much previous study determined the factors affecting mobile learning quality, seldom research works discussed the influence weights of the elements and their interrelations in the higher education through a comprehensive view. Hence, the purpose of this research is to explore the interrelationships and feedback between the factors affecting mobile learning quality via a combined multiple attribute decision-making (MADM) method, which will include decision-making trial and evaluation laboratory (DEMATEL), and DEMATEL-based ANP (DANP) approaches. This recommended approach can offer guidance to prioritize the influence elements in the enhancement plans for mobile learning quality. This research uses the recommended approach in the higher education in Taiwan as an empirical study during COVID-19. These findings results state which service quality needs to be enhanced primarily, and learning ability is the most important factor influencing mobile learning quality during COVID-19. Furthermore, the results show that system quality perspective has the strongest impact on the relations and it also has an important effect on other perspectives. The results can provide guidance on assigning resources of limit to improve this mobile learning quality in Taiwanese higher education in the COVID-19 pandemics.

This study examines how maximum emotional intelligence (EI) members can contribute to the emergence of team-level organizational citizenship behaviors (OCB). Based on integrating a strategic core role and multilevel theory, we developed and tested a model in which the maximum EI score in teams results in intrateam trust and consequently impacts team OCB and examined whether the indirect effect of maximum EI on team OCB through intrateam trust would be moderated by EI diversity and trust divergence in teams. The results from 129 project teams showed that the relationship of maximum EI with team OCB is mediated by intrateam trust and this relationship is stronger for lower levels of EI diversity and trust divergence than for higher levels of diversity and divergence. The findings advance our understanding of the role of EI in team settings. Our research has important implications for organizations attempting to develop the applied value of EI.

Spent coffee grounds (SCGs) are waste residues arising from the process of coffee brewing and are usually sent to landfills, causing environmental concerns. SCGs contain a considerable amount of fatty acids and is therefore a promising green alternative bio-based phase change material (PCMs) compared to conventional organic and inorganic PCMs. In this study, the extraction of coffee oil from SCGs was conducted using three different organic solvents-ethanol, acetone, and hexane. The chemical composition, chemical, and thermophysical properties of these coffee oil extracts were studied to evaluate their feasibility as a bio-based PCM. Gas chromatography-mass spectroscopy (GC-MS) analysis indicated that coffee oil contains about 60-80 % of fatty acids while the phase transition temperature of the coffee oil extracts is approximately 4.5 ± 0.72 °C, with latent heat values of 51.15 ± 1.46 J/g as determined by differential scanning calorimetry (DSC). Fourier Transform Infrared Spectroscopy (FTIR) and DSC results of coffee oil extracts after thermal cycling revealed good thermal and chemical stability. An application study to evaluate coffee oil extract as a potential cold therapy modality showed that it can maintain temperatures below normal body temperature for up to 46 min. In conclusion, this work exemplifies the potential of SCGs as a promising green and sustainable resource for bio-based PCMs for low-temperature thermal energy storage applications such as cold-chain transportation and cold therapy.

For the first time, we demonstrate a Ti-MOF (Ti-metal organic framework) single-crystal featuring an intracrystal macro-microporous hierarchy (Hier-NTU-9) by a vapor-assisted polymer-templated method. This Hier-NTU-9 possesses macropores (100-1000 nm) derived from polymer templates and enhanced transport ability of bulky molecules, exhibiting almost double the desulfurization activity compared to the conventional NTU-9.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENTItch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

Specificity and efficiency of plant virus transmission depend largely on protein-protein interactions of vectors and viruses. Cucurbit chlorotic yellows virus (CCYV), transmitted specifically by tobacco whitefly, Bemisia tabaci, in a semi-persistent manner, has caused serious damage on cucurbit and vegetable crops around the world. However, the molecular mechanism of interaction during CCYV retention and transmission are still lacking. CCYV was proven to bind particularly to the whitefly foregut, and here, we confirmed that the minor coat protein (CPm) of CCYV is participated in the interaction with the vector. In order to identify proteins of B. tabaci that interact directly with CPm of CCYV, the immunoprecipitation (IP) assay and DUALmembrane cDNA library screening technology were applied. The cytochrome c oxidase subunit 5A (COX), tubulin beta chain (TUB) and keratin, type I cytoskeletal 9-like (KRT) of B. tabaci shown strong interactions with CPm and are closely associated with the retention within the vector and transmission of CCYV. These findings on whitefly protein-CCYV CPm interactions are crucial for a much better understanding the mechanism of semi-persistent plant virus transmission by insect vectors, as well as for implement new strategies for effective management of plant viruses and their vector insects.

This study aimed to examine the associations between perceived social support, perceived competence, and physical activity in children with physical and intellectual disabilities during the COVID-19 pandemic. During the third wave of the pandemic in Hong Kong (i.e., July through December 2020), 291 participants age 6–17 years from 27 special schools were included. After controlling for demographic variables, the total variance explained by perceived social support and perceived competence was 24%, F(2, 240) = 12.42, p p p = .22). This study highlights two key facilitators for shaping physical activity involvement among children with disabilities during the COVID-19 pandemic.

This study aimed to investigate the effect of dexamethasone (DEX) on chemotaxis and phagocytic activity of neutrophils for spermatozoa and semen quality of preserved boar semen. The different concentrations of dexamethasone were added to boar semen dilutions to detect its effects on the chemotaxis of neutrophils and phagocytosis of neutrophils and sperm motility sperm malformation rate, plasma membrane integrity, mitochondrial activity, and spermatozoa motility parameters. The study results showed that the experimental groups of DEX significantly inhibited the phagocytosis and chemotaxis of PMNs for spermatozoa. With the increased concentration of DEX, there was an inhibition effect on PMNs activity. In addition, under 17 °C storage conditions, the addition of DEX 1 × 10

Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disorder characterized by autoantibodies against the glomerular and alveolar basement membranes, leading to rapidly progressive glomerulonephritis and severe alveolar hemorrhage. The noncollagenous domain of the α3 chain of type IV collagen, α3(IV)NC1, contains the main target autoantigen in this disease. Epitope mapping studies of α3(IV)NC1 have identified several nephritogenic epitopes and critical residues that bind to autoantibodies and trigger anti-GBM disease. The discovery of novel target antigens has revealed the heterogeneous nature of this disease. In addition, both epitope spreading and mimicry have been implicated in the pathogenesis of anti-GBM disease. Epitope spreading refers to the development of autoimmunity to new autoepitopes, thus worsening disease progression, whereas epitope mimicry, which occurs via sharing of critical residues with microbial peptides, can initiate autoimmunity. An understanding of these autoimmune responses may open opportunities to explore potential new therapeutic approaches for this disease. We review how current advances in epitope mapping, identification of novel autoantigens, and the phenomena of epitope spreading and mimicry have heightened the understanding of autoimmunity in the pathogenesis of anti-GBM disease, and we discuss prospects for immunotherapy.

Three new 3D TMeQ[6]-based coordination polymers of alkali-earth metal ions (Ca2+, Sr2+ and Ba2+) were characterized, and one can highly selectively detect NFX (norfloxacin) molecules via a fluorescence quenching effect.

Pre-diagnostic higher vitamin C and β-carotene intake was associated with improved ovarian cancer survival.

This review gives an explicit overview of developments in the vapor-phase dehydration of lactic acid to acrylic acid with the rational design of heterogeneous catalyst systems. Constructive critiques are presented.

Presented here are the structure, optical properties, photocurrent response and theoretical study of a non-perovskite copper iodobismuthate hybrid, namely, [(Me)2-(DABCO)]2Cu2Bi2I12 (1).

In educational and psychological research, the logit and probit links are often used to fit the binary item response data. The appropriateness and importance of the choice of links within the item response theory (IRT) framework has not been investigated yet. In this paper, we present a family of IRT models with generalized logit links, which include the traditional logistic and normal ogive models as special cases. This family of models are flexible enough not only to adjust the item characteristic curve tail probability by two shape parameters but also to allow us to fit the same link or different links to different items within the IRT model framework. In addition, the proposed models are implemented in the Stan software to sample from the posterior distributions. Using readily available Stan outputs, the four Bayesian model selection criteria are computed for guiding the choice of the links within the IRT model framework. Extensive simulation studies are conducted to examine the empirical performance of the proposed models and the model fittings in terms of “in-sample” and “out-of-sample” predictions based on the deviance. Finally, a detailed analysis of the real reading assessment data is carried out to illustrate the proposed methodology.

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4–12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (−0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

ObjectivesThe primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022.Eligibility criteriaQuantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included.ResultsTwenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, pConclusionMale sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

Previous research has shown the relationship between loneliness and affect, as well as the relationship between trait loneliness and state loneliness. However, none has investigated how social context affects the association between loneliness and affect. The current study aims to examine the association between trait loneliness, state loneliness and momentary affects in different social contexts.Participants aged 15-24 were randomly recruited from a Hong Kong epidemiological study to participate in an Experience Sampling Method (ESM) study. The group was divided in two based on the mean trait loneliness score (UCLA Loneliness Scale) at baseline. State loneliness, momentary positive (PA) and negative affect (NA) and social context were assessed using ESM. Multilevel logistic regression was used to analyze the association between momentary affect, state loneliness and trait loneliness in various social contexts.HL (high lonely) and LL (low lonely) groups consisted of 79 participants (44.6%) and 98 participants (55.4%) respectively. HL group had lower PA and higher NA, as well as a higher state loneliness than LL group. HL group had a lower state loneliness when being with intimate company compared to alone. LL group only had a higher PA when being with intimate company compared to non-intimate company and alone respectively.Adolescents with high level of trait loneliness experienced higher PA, momentary loneliness and lower NA compared to those with low level of trait loneliness. The quality of social company is crucial in allowing one to experience different degrees of PA and momentary loneliness.

Autism spectrum disorders caused by both genetic and environmental factors are strongly male-biased neuropsychiatric conditions. However, the mechanism underlying the sex bias of autism spectrum disorders remains elusive. Here, we use a mouse model in which the autism-linked gene Cttnbp2 is mutated to explore the potential mechanism underlying the autism sex bias. Autism-like features of Cttnbp2 mutant mice were assessed via behavioural assays. C-FOS staining identified sex-biased brain regions critical to social interaction, with their roles and connectivity then validated by chemogenetic manipulation. Proteomic and bioinformatic analyses established sex-biased molecular deficits at synapses, prompting our hypothesis that male-biased nutrient demand magnifies Cttnbp2 deficiency. Accordingly, intakes of branched-chain amino acids (BCAA) and zinc were experimentally altered to assess their effect on autism-like behaviours. Both deletion and autism-linked mutation of Cttnbp2 result in male-biased social deficits. Seven brain regions, including the infralimbic area of the medial prefrontal cortex (ILA), exhibit reduced neural activity in male mutant mice but not in females upon social stimulation. ILA activation by chemogenetic manipulation is sufficient to activate four of those brain regions susceptible to Cttnbp2 deficiency and consequently to ameliorate social deficits in male mice, implying an ILA-regulated neural circuit is critical to male-biased social deficits. Proteomics analysis reveals male-specific downregulated proteins (including SHANK2 and PSD-95, two synaptic zinc-binding proteins) and female-specific upregulated proteins (including RRAGC) linked to neuropsychiatric disorders, which are likely relevant to male-biased deficits and a female protective effect observed in Cttnbp2 mutant mice. Notably, RRAGC is an upstream regulator of mTOR that senses BCAA, suggesting that mTOR exerts a beneficial effect on females. Indeed, increased BCAA intake activates the mTOR pathway and rescues neuronal responses and social behaviours of male Cttnbp2 mutant mice. Moreover, mutant males exhibit greatly increased zinc demand to display normal social behaviours. Mice carrying an autism-linked Cttnbp2 mutation exhibit male-biased social deficits linked to specific brain regions, differential synaptic proteomes and higher demand for BCAA and zinc. We postulate that lower demand for zinc and BCAA are relevant to the female protective effect. Our study reveals a mechanism underlying sex-biased social defects and also suggests a potential therapeutic approach for autism spectrum disorders.

Summary Background Individuals who suffered a neurological adverse event after the Coronavirus disease (COVID-19) vaccine could hesitate and defer reimmunization. Aim We examine the risk of recurrence following reimmunization among patients who developed a neurological event after the first dose of the COVID-19 mRNA vaccine. Design Observational study. Methods Individuals who developed an adjudicated neurological adverse event (based on Brighton Collaboration criteria) within 6 weeks of the first dose of the COVID-19 vaccine requiring hospitalization were enrolled into a multicenter national registry in Singapore. Neurological recurrence, defined by the development of another neurological event within 6 weeks of the second vaccine dose, was reviewed. Clinical characteristics were compared between patients who chose to proceed or withhold further vaccination, and between those who received timely (3–6 weeks) or delayed (>6 weeks) reimmunization. Results From 235 patients (median age, 67 years; 63% men) who developed an adjudicated neurological event after their first dose of mRNA vaccine between 30 December 2020 and 20 April 2021, 181 (77%) chose to undergo reimmunization. Those who decided against reimmunization were older (median age, 74 vs. 66 years) and had greater physical disability following their primary neurological event (46% vs. 20%, P Conclusions A prior neurological event should not necessarily preclude reimmunization and the decision to proceed with reimmunization should consider the overwhelming benefits conferred by vaccination toward ending this pandemic.

AimsThe detection of white-coat hypertension/white-coat uncontrolled hypertension (WCH/WUCH) with out-of-office blood pressure (BP) monitoring is time- and resource-consuming. We aim to develop a machine learning (ML)-derived prediction model based on the characteristics of patients from a single outpatient visit.Methods and resultsData from two cohorts in Taiwan were used. Cohort one (970 patients) was used for development and internal validation, and cohort two (464 patients) was used for external validation. WCH/WUCH was defined as an office BP of ≥140/90 mmHg and daytime ambulatory BP of ConclusionOur prediction models achieved good performance, underlining the feasibility of applying ML models to outpatient populations for the diagnosis of WCH and WUCH. Further validation with other prospective data sets should be considered in the future.

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokinesuppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-ɣ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.