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Ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed.In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p-, m-, and o-ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two-electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m-ABFIP exhibited the most significant difference of insecticidal activity by about 90- and 5-fold to mosquito larvae between non-irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m-ABFIP and DTFIP1 enable optical control over the homomeric LsRDL-type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)-type GABAR by photoisomerization.Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA-dependent behavior. © 2022 Society of Chemical Industry.

Falls in older adulthood can have serious consequences. It is therefore important to identify ways to prevent falls, particularly from the voice of older adults. Bottom-up qualitative exploration of the perspectives of older adults can provide rich insights that can help inform the development of effective fall prevention programmes. However, currently there is a dearth of such empirical data, especially among urban-dwelling older adults in high-density cities where fall rates are high. The current study aimed to examine qualitatively perceptions of neighbourhood physical environment in relation to falls, perceived risks and fear of falling, and strategies and behaviours for fall prevention in a sample of urban-dwelling older adults in the high-density city of Hong Kong. Face-to-face semi-structured in-depth interviews were conducted with 50 community-dwelling older adults. Interviews were transcribed verbatim and analysed using thematic analysis techniques. Five general themes were revealed: risks and circumstances of falls, consequences of falls, fear of falling and its consequences, neighbourhood environment, and strategies and behaviours of fall prevention. While older adults discussed the risks of falling and held a fear of falling, these beliefs were mixed. In addition to fall prevention strategies (e.g. keep balance), current findings highlighted the importance of establishing protective factors (e.g. flat and even walking paths) and reducing risk factors (e.g. neighbourhood clutter) in neighbourhood environments. For urban-dwelling older adults in high-density cities, current findings highlight the importance of focusing efforts at the built environment level in addition to strategies and behaviours of fall prevention at the individual level.

The dynamic three-dimensional structures of chromatin and extrachromosomal DNA molecules regulate fundamental cellular processes and beyond. However, the visualization of specific DNA sequences in live cells, especially nonrepetitive sequences accounting for most of the genome, is still vastly challenging. Here, we introduce a robust CRISPR-mediated fluorescence in situ hybridization amplifier (CRISPR FISHer) system, which exploits engineered sgRNA and protein trimerization domain-mediated, phase separation-based exponential assembly of fluorescent proteins in the CRISPR-targeting locus, conferring enhancements in both local brightness and signal-to-background ratio and thus achieving single sgRNA-directed visualization of native nonrepetitive DNA loci in live cells. In one application, by labeling and tracking the broken ends of chromosomal fragments, CRISPR FISHer enables real-time visualization of the entire process of chromosome breakage, separation, and subsequent intra- or inter-chromosomal ends rejoining in a single live cell. Furthermore, CRISPR FISHer allows the movement of small extrachromosomal circular DNAs (eccDNAs) and invading DNAs to be recorded, revealing substantial differences in dynamic behaviors between chromosomal and extrachromosomal loci. With the potential to track any specified self or non-self DNA sequences, CRISPR FISHer dramatically broadens the scope of live-cell imaging in biological events and for biomedical diagnoses.

This longitudinal study applied the integrated model of self-determination theory (SDT) and the theory of planned behaviour (TPB) to explain COVID-19 preventive behaviours among parents of young children in the United States.The study adopted a two-wave longitudinal study design. Parents (The parameter estimates of the model (CFI.96, TLI.86, RMSEA = .05, SRMR = .03) fit acceptably well to the data. Psychological need support was positively and significantly linked to autonomous and controlled motivation and amotivation. Autonomous motivation was positively and significantly correlated with TPB factors, and intention. Intention was a significant and positive predictor of behavioural adherence.The integrated model of SDT and the TPB appeared to be applicable to the explanation of COVID-19 prevention among the U.S. parents. Longitudinal data showed that a psychological need supportive social environment was related to favourable motivation, social cognition beliefs, intention and behavioural adherence to the preventive behaviours of parents protecting their young children from COVID-19.

In Antarctica, excellent astronomical observing conditions have been measured at Dome A during night-time (or polar winter). This study investigates the performance of the Polar-optimized version of the Weather Research and Forecasting (Polar WRF, PWRF hereafter) for simulating the night-time astronomical seeing at Dome A. The seeing values were estimated by a seeing model, which used the PWRF-simulated wind speed and temperature as inputs. Furthermore, three methods to obtain the boundary layer height in the seeing model have been examined. The estimated seeing agrees well with 50-d measurements from the KunLun Differential Image Motion Monitor at Dome A during the night-time of 2019; the correlation coefficients range from 0.62 to 0.71. The PWRF-simulated meteorological parameters indicate that low wind speed and strong temperature inversion (when a large gradient Richardson number always occurs) near the ground can lead to good seeing condition. The results suggest that the PWRF model could be a reliable tool for scheduling observational astronomy at Dome A during night-time.

Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.

Astronomical seeing is important for monitoring the atmospheric environment, observation scheduling and management, and selecting astronomical sites. This study first attempts to establish a near-global astronomical seeing map by employing the fifth European Centre for Medium-Range Weather Forecasts Reanalysis (ERA5) data combined with the estimated model. Then, some example sites’ results from ERA5 were compared against the astronomical seeing results from the balloon-borne microthermal measurements and the differential image motion monitor (DIMM) instrument. The global astronomical seeing variations exhibit large spatial dependence. The best seeing areas are generally discerned over the mid-latitude regions, consistent with the regions of the European Southern Observatory and Tibetan Plateau. In addition, the astronomical seeing values of the Tibetan Plateau in spring are better than in the other seasons. The site results from ERA5 show that the astronomical seeing values of some example sites are generally consistent with the measurements. Overall, the global astronomical seeing map presented in this study can provide a reference and basis to further understand the astronomy site selection and optoelectronics equipment observation path selection.

BackgroundFrailty predicts an increased risk of postoperative morbidity and mortality. Comparison of the predictive performance between two deficit accumulation models of frailty, the modified frailty index (mFI) and the revised-Risk Analysis Index (RAI-rev), is poorly understood. This study compared the predictive abilities of the above two frailty indices in predicting life-threatening morbidity and mortality among older patients following elective high-risk abdominal surgery.MethodsThis retrospective cohort study extracted perioperative data of older patients (age ≥65 years) undergoing elective high-risk abdominal surgery at a single institution between January 2018 and December 2020. Preoperative frailty was screened by mFI and RAI-rev scoring systems. The primary outcome was the composite of postoperative life-threatening morbidity and mortality during hospitalization. Multivariable logistic regression analyses were performed to investigate the association of the two frailty indices with the primary outcome. Receiver-operating characteristic (ROC) curve was employed to test the predictive performances of the two frailty instruments in predicting the composite primary outcome. The difference between the area under the curves (AUCs) was assessed by DeLong’s test.Results1,132 older patients (mean age, 73.4 ± 6.2 years; 63.9% male) were included. Of these, 107 (9.5%) developed postoperative life-threatening morbidity and mortality. In multivariable logistic regression analyses, rising continuous frailty scores (mFI: adjusted OR 1.319 per 0.09-point increase in score, 95% CI 1.151–1.511, p p = 0.002) as well as dichotomized frailty measures (mFI ≥0.27: adjusted OR 2.059, 95% CI 1.328–3.193, p = 0.001; RAI-rev ≥45: adjusted OR 1.862, 95% CI 1.188–2.919, p = 0.007) were associated with increased odds of the primary outcome separately. ROC curve analysis showed that the discrimination of mFI and RAI-rev scores for the life-threatening morbidity and mortality was poor and comparable (AUC: 0.598 [95% CI 0.569–0.627] vs. 0.613 [95% CI 0.583–0.641]; DeLong’s test: Z = 0.375, p = 0.7075).ConclusionHigh mFI and RAI-rev scores were associated with an increased risk of life-threatening morbidity and mortality in older patients undergoing elective high-risk abdominal surgery. However, both frailty indices displayed poor discrimination for postoperative life-threatening morbidity and mortality.

ST1: Composition of the modified AIN-93G diet used in the animal experiment; ST2: Sequences of primers in qRT-PCR; ST3: Concentrations of lipid mediators in the plasma of control mice (not treated with AOM/DSS) and colon cancer mice (treated with AOM/DSS); ST4: Concentrations of lipid mediators in the colon of control mice (not treated with AOM/DSS) and colon cancer mice (treated with AOM/DSS); ST5: Concentrations of lipid mediators in the colon of AOM/DSS-treated Cyp2c+/+ and Cyp2c+/- mice.

Colon cancer is the third most common cancer and the second leading cause of cancer-related death in the United States, emphasizing the need for the discovery of new cellular targets. Using a metabolomics approach, we report here that epoxygenated fatty acids (EpFA), which are eicosanoid metabolites produced by cytochrome P450 (CYP) monooxygenases, were increased in both the plasma and colon of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. CYP monooxygenases were overexpressed in colon tumor tissues and colon cancer cells. Pharmacologic inhibition or genetic ablation of CYP monooxygenases suppressed AOM/DSS-induced colon tumorigenesis in vivo. In addition, treatment with 12,13-epoxyoctadecenoic acid (EpOME), which is a metabolite of CYP monooxygenase produced from linoleic acid, increased cytokine production and JNK phosphorylation in vitro and exacerbated AOM/DSS-induced colon tumorigenesis in vivo. Together, these results demonstrate that the previously unappreciated CYP monooxygenase pathway is upregulated in colon cancer, contributes to its pathogenesis, and could be therapeutically explored for preventing or treating colon cancer.Significance:This study finds that the previously unappreciated CYP monooxygenase eicosanoid pathway is deregulated in colon cancer and contributes to colon tumorigenesis.

Supplementary Materials and Methods

SF1: CYP monooxygenase expression in human colon cancer cells; SF2: gene expression of Cyp2e1 in the liver of Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF3: liver inflammation in Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF4: survival curve of the AOM/DSS-stimulated Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF5: pharmacological inhibition of CYP monooxygenases suppresses AOM/DSS-induced colon tumorigenesis in mice; SF6: effects of 12,13-EpOME on MC38 tumor growth in C57BL/6 mice; SF7: mRNA expression levels of CYP monooxygenases in control subjects and colon cancer patients

The relationship between the severity of impairment in basic activities of daily living (ADLs) function and postoperative outcomes in older surgical patients remains unclear. This study aimed to clarify the association between the severity of preoperative functional impairment and the composite postoperative outcome of major morbidity and mortality in older patients undergoing digestive tract surgery.This was a retrospective cohort study. We collected perioperative data of older patients (age ≥ 65 years) who underwent digestive tract surgery in our institution. The severity of functional impairment was assessed using the Barthel Index scale before surgery. The major morbidity and mortality were defined as Clavien-Dindo grade III or greater postoperative complications during hospital stay. The association between the severity of functional impairment and the major morbidity and mortality was assessed using a multivariable logistic regression model.131 of 1076 patients (12.2%) developed major morbidity and mortality. After controlling for confounding factors, high Barthel Index scores were correlated with decreased risk of major morbidity and mortality (OR 0.986, 95% CI 0.976-0.997, P = 0.011); preoperative severe (OR 2.862, 95% CI 1.172-6.989, P = 0.021), but not mild or moderate (OR 1.019, 95% CI 0.602-1.726, P = 0.943) functional impairment was independently associated with an increased risk of major morbidity and mortality, when compared with independent functional status.Preoperative severe functional impairment in basic ADLs was independently associated with a higher risk of major postoperative morbidity and mortality in older patients undergoing digestive tract surgery.

Strong seedlings are essential for high yield. To explore the foundation of strong seedlings, we investigated various factors influencing the conversion and distribution of seed storage reserves during seedling establishment in maize inbred lines. Three maize inbred lines were used to explore the effects of seed size, seed vigor, illumination duration, temperature, water content, and salt concentration of the seedling medium on the utilization of seed storage reserves during seedling establishment. The results showed that the conversion rate of small seeds was 3.69 to 17.71% higher than that of large seeds. Moreover, prolonged illumination time was conducive to the formation of strong seedlings. However, low temperature, drought stress and salt stress reduced the conversion rate of seed storage reserves and increased the root/shoot ratio. These results could be used to guide field management during seedling emergence and develop improved germplasm with a high conversion rate of seed storage reserves.

To evaluate the effect of intensive oropharyngeal functional training on swallowing in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.Fourteen patients with nasopharyngeal carcinomas and dysphagia after radiotherapy received intensive oropharyngeal training for two weeks. The Functional Oral Intake Scale (FOIS) and videofluoroscopic swallowing studies (VFSS) were used to evaluate swallowing function before and after intensive oropharyngeal training. Spatiotemporal parameters of the VFSS were analyzed using a digital image analysis system.After training, the FOIS, Rosenbek penetration-aspiration score, DIGEST, normalized residue ratio scale, and spatiotemporal parameters of VFSS were significantly improved (P 0.05).This study indicated that intensive oropharyngeal training improves swallowing function after radiotherapy in patients with nasopharyngeal carcinoma.

Purpose The purpose of this paper is to demonstrate the applicability of the Credit Default Swaps (CDS), as a financial instrument, for transferring of risk in project finance loans. Also, an equation has been derived for pricing of CDS spreads. Design/methodology/approach The debt service cover ratio (DSCR) is modeled as a Brownian Motion (BM) with a power-law model fitted to the mean and half-variance of the existing data set of DSCRs. The survival probability of DSCR is calculated during the operational phase of the project finance deal, using a closed-form analytical method, and the results are verified by Monte Carlo simulation (MCS). Findings It is found that using the power-law model yields higher CDS premiums. This in turn confirms the necessity of conducting rigorous statistical analysis in fitting the best performing model as uninformed reliance on constant time-invariant drift and diffusion model can erroneously result in smaller CDS spreads. A sensitivity analysis also shows that the results are very sensitive to the recovery rate and cost of debt values. Originality/value Insufficiency of free cash flow is a major risk in the toll road project finance and hence there is a need to develop innovative financial instruments for risk management. In this paper, a novel valuation method of CDS is proposed assuming that DSCR follows the BM stochastic process.

On-site observations show that several damages have occurred in CRTS II slab-type ballastless track system, such as crack and interface debonding between different structural layers, which will trigger the occurrence of some failure modes of CRTS II track slab. As the damages are the prior for specific failure modes, time-dependent reliability of CRTS II track slab should be conducted considering the uncertainties associated with both the failure mode and the damage, which is defined as the conditional time-dependent reliability in this study. To appropriately express the causal relationship among the failure modes and prior damages, a conditional limit state function (LSF) model is proposed with explicit expressions provided. With the aid of the proposed model, conditional time-dependent reliability of CRTS II track slab for two individual failure modes are investigated, which are the steel yielding failure mode under longitudinal cracking, and the vertical instability failure mode under interface debonding. Furthermore, conditional time-dependent system reliability of the track slab has also been analyzed considering four safety failure modes. The advantage of the proposed method is that prior damages have been accounted in establishing the failure criteria and incorporated in the formulation of time-dependent reliability, which provides a general formwork for structural reliability involving the causal relationship among the failure modes and damages.

As an evolutional concept of aero engine, the variable cycle engine (VCE) can adjust the thermodynamic cycle via working on different modes to meet different flight missions. These working modes lead to the performance and stability of variable geometries for mode switching under different mission profiles. This paper aims at the performance prediction under different working conditions on the key variable geometry, namely, the forward variable area bypass injector (FVABI). The rotary and translating mathematical calculation models are established and validated via the three-dimensional numerical simulation. It considers the choked flow state caused by area change at FVABI and mode selector valve (MSV). The variable geometry schedules at the typical subsonic cruise working condition are analyzed based on the zero-dimensional engine performance model. It verifies the efficiency of the improved zero-dimensional bypass mixing calculation model to predict the mixing characteristics of the FVABI on different operating modes. The maximum error of the total pressure recovery coefficient and the ejection ratio is 2.3% and 6.2%, respectively. This performance prediction method can lay foundations for the variable geometry design and performance optimization of the VCE under typical mission profiles.

The aging Chinese population is growing fast, and the proportion of the population aged 60 years old is projected to reach 28% by 2040, estimated 402 million. With increased life expectancy, the aging population tends to suffer from health risks and diseases, which create a burden on public health policy. Hence, it is essential to promote healthy and active aging, which includes improving older adults' physical and mental capacities and advocating for the achievement of a healthy life expectancy. Despite the rapidly growing aging population in China, there have been no reviews investigating the effect of physical activity on physical and mental health among older Chinese adults. Therefore, the current study aimed to review studies from the past 15 years that illustrate the effect of physical activity on physical and mental health among Chinese older adults. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR), this review addresses the associations between physical activity, physical health and mental health among older Chinese adults. A total of 371 studies were included in the scoping review, which covered the relationships between physical activity, physical health and mental health variables. The scoping review also revealed the impact of various kinds of physical activity affecting older adults' physical health, such as functional fitness, body composition, fall risk and balance, and mental health issues, such as depression, anxiety, cognitive function and quality of life. Moreover, studies have identified innovative forms of physical activity as emerging trends in physical activity interventions for older adults. To conclude, this scoping review captured the common effects between physical activity and overall wellbeing, including physical, mental, and cognitive health. Additionally, diverse forms of physical activity intervention, such as group-based and supervised individual interventions, should be supported, and cross-cultural exercise comparisons should be made in future explorations.

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD-1), are increasingly prescribed in metastatic carcinoma therapy. ICI-related kidney injury is gradually recognized by clinicians. However, immune-related ureteritis and cystitis easily go undiagnosed. We report three cases of PD-1 monoclonal antibody (mAb)-related ureteritis and cystitis. We further carried out a review of the literature about ICI-related ureteritis and cystitis. The cases in our reports manifest urinary irritation, sterile pyuria, gross hematuria, hydronephrosis, dilation of the ureters, and acute kidney injury. Urinary irritation improved effectively; urinalysis and renal function returned to normal after glucocorticoid therapy. During ICI therapy, urinalysis and renal function and urinary imaging examination are recommended to be monitored regularly. It contributes to identify immune-related ureteritis/cystitis earlier to efficiently alleviate urinary symptoms and immunologic urinary tract injury through glucocorticoid therapy while avoiding the abuse of antibiotics.

Background Broflanilide has been registered in China for control of Lepidoptera and Coleoptera pests, and it is widely used to control the target pests on lethal and sublethal levels. Therefore, lethal and sublethal effects of broflanilide to the common cutworm (CCW) Spodoptera litura Fabricius, a representative lepidopteran pest in agricultural crops, were examined to explore its ecological influence to pests in this study. Results To F0 , broflanilide had little influence on hatchability of eggs, but significantly reduced the survival rate of neonate. The lethal activity of broflanilide to 3rd instar larvae and adults was 0.13 mg/kg (LD50 ) and 3.59 mg/L (LC50 ) respectively at 48 h. After treated by sublethal dose (LD10 and LD30 ) of broflanilide, the duration from 3rd to 6th instar larvae and the mean fecundity of reproductive females were significantly increased, but the pupation rate, weight of pupae, and life cycle rate were significantly decreased. In F1 , the duration of F1 larvae and the doubling time was prolonged, whereas the rates of pupation and the life cycle were decreased by 14.92% and 18.00%, respectively. The intrinsic rate of increase, finite rate of increase and net reproductive rate of sublethal group were lower than the control group. The relative fitness of F1 treated by LD10 and LD30 was 0.81 and 0.66, respectively. Conslusion Broflanilide not only has highly lethal activity, but also suppresses the population growth and the progeny of CCW, which is a critical factor for guideline of its usage in the field. This article is protected by copyright. All rights reserved.