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Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated. Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period. Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells. Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Migratory divides are contact zones between breeding populations with divergent migratory strategies during the nonbreeding season. These locations provide an opportunity to evaluate the role of seasonal migration in the maintenance of reproductive isolation, particularly the relationship between population structure and features associated with distinct migratory strategies. We combine light-level geolocators, genomic sequencing, and stable isotopes to investigate the timing of migration and migratory routes of individuals breeding on either side of a migratory divide coinciding with genomic differentiation across a hybrid zone between barn swallow (Hirundo rustica) subspecies in China. Individuals west of the hybrid zone, with H. r. rustica ancestry, had comparatively enriched stable-carbon and hydrogen isotope values and overwintered in eastern Africa, whereas birds east of the hybrid zone, with H. r. gutturalis ancestry, had depleted isotope values and migrated to southern India. The two subspecies took divergent migratory routes around the high-altitude Karakoram Range and arrived on the breeding grounds over 3 weeks apart. These results indicate that assortative mating by timing of arrival and/or selection against hybrids with intermediate migratory traits may maintain reproductive isolation between the subspecies, and that inhospitable geographic features may have contributed to the diversification of Asian avifauna by influencing migratory patterns.

Workers of Apis cerana cerana undergo an in-hive nursing to outdoor foraging transition, but the genes underlying this age-related transition remain largely unknown. Here, we sequenced the head transcriptomes of its 7-day-old normal nurses, 18- and 22-day-old normal foragers, 7-day-old precocious foragers and 22-day-old over-aged nurses to unravel the genes associated with this transition. Mapping of the sequence reads to Apis mellifera genome showed that the three types of foragers had a greater percentage of reads from annotated exons and intergenic regions, whereas the two types of nurses had a greater percentage of reads from introns. Pair- and group-wise comparisons of the five transcriptomes revealed 59 uniquely expressed genes (18 in nurses and 41 in foragers) and 14 nurse- and 15 forager-upregulated genes. The uniquely expressed genes are usually low-abundance long noncoding RNAs, transcription factors, transcription coactivators, RNA-binding proteins, kinases or phosphatases that are involved in signaling and/or regulation, whereas the nurse- or forager-upregulated genes are often high-abundance downstream genes that directly perform the tasks of nurses or foragers. Taken together, these results suggest that the nurse-forager transition is coordinated by a social signal-triggered epigenetic shift from introns to exons/intergenic regions and the resulting transcriptional shift between the nurse- and forager-associated genes.

There has been a growing interest in understanding whether and how people adapt to extreme weather events in a changing climate. This article presents one of the first empirical analyses of adaptation to flooding on a global scale. Using a sample of 97 countries between 1985 and 2010, we investigate the extent and pattern of flood adaptation by estimating the effects of a country's climatological risk, recent flood experiences, and socioeconomic characteristics on its flood-related fatalities. Our results provide mixed evidence on adaptation: countries facing greater long-term climatological flooding risks do not necessarily adapt better and suffer fewer fatalities; however, after controlling for the cross-country heterogeneity, we find that more recent flooding shocks have a significant and negative effect on fatalities from subsequent floods. These findings may suggest the short-term learning dynamics of adaptation and potential inefficacy of earlier flood control measures, particularly those that promote increased exposure in floodplains. Our findings provide important implications for climate adaptation policy making and climate modeling.

The application of double electron‐electron resonance (DEER) with site‐directed spin labeling (SDSL) to measure distances in proteins and protein complexes in living cells puts rigorous restraints on the spin‐label. The linkage and paramagnetic centers need to resist the reducing conditions of the cell. Rigid attachment of the probe to the protein improves precision of the measured distances. Here, three two‐armed GdIII complexes, GdIII‐CLaNP13a/b/c were synthesized. Rather than the disulfide linkage of most other CLaNP molecules, a thioether linkage was used to avoid reductive dissociation of the linker. The doubly GdIII labeled N55C/V57C/K147C/T151C variants of T4Lysozyme were measured by 95 GHz DEER. The constructs were measured in vitro, in cell lysate and in Dictyostelium discoideum cells. Measured distances were 4.5 nm, consistent with results from paramagnetic NMR. A narrow distance distribution and typical modulation depth, also in cell, indicate complete and durable labeling and probe rigidity due to the dual attachment sites., Two armed and ready! A two armed, thus rigid, GdIII‐CLaNP13 probe for double electron–electron resonance (DEER) measurements on proteins can be used to measure nanometer distances in cells with high precision.

Atomically thin bismuth oxyselenide (Bi2 O2 Se) exhibits attractive properties for electronic and optoelectronic applications, such as high charge-carrier mobility and good air stability. Recently, the development of Bi2 O2 Se-based heterostructures have attracted enormous interests with promising prospects for diverse device applications. Although the electrical properties of Bi2 O2 Se-based heterostructures have been widely studied, the interlayer charge transfer in these heterostructures remains elusive, despite its importance in harnessing their emergent functionalities. Here, a comprehensive experimental investigation on the interlayer charge transfer properties of two heterostructures formed by Bi2 O2 Se and representative transition metal dichalcogenides (namely, WS2 /Bi2 O2 Se and MoS2 /Bi2 O2 Se) is reported. Kelvin probe force microscopy is used to measure the work functions of the samples, which are further employed to establish type-II band alignment of both heterostructures. Photoluminescence quenching is observed in each heterostructure, suggesting high charge transfer efficiency. Time-resolved and layer-selective pump-probe measurements further prove the ultrafast interlayer charge transfer processes and formation of long-lived interlayer excitons. These results establish the feasibility of integrating 2D Bi2 O2 Se with other 2D semiconductors to fabricate heterostructures with novel charge transfer properties and provide insight for understanding the performance of optoelectronic devices based on such 2D heterostructures.

Parent birds show a continuous spectrum of breeding strategies, ranging from a low-fecundity and high-survival pattern to a high-fecundity, low-survival pattern. Investigations of parental breeding strategies under variable environmental conditions can illustrate how parents trade-off the benefits and costs of these two extreme strategies. White-collared Blackbirds Turdus albocinctus can breed twice a year on the Tibetan Plateau. We show that both life-history traits and parental feeding behaviour differ between these two breeding attempts. In the first attempt, the birds produced small clutches and fledged a small number of nestlings of high body condition. In the second attempt, they produced larger clutches and fledged more nestlings of lower body condition. Males made greater contributions to brood provisioning compared with females in the first attempt but there was no sex difference in brood provisioning in the second attempt. In the first attempt, producing smaller clutches can shorten the nestling period, and the increased male contribution to brood provisioning can protect the energy reserves of females. Thus, females can begin a second attempt sooner and produce larger clutches. During the second nesting attempt, when conditions are warmer and wetter, parents rely on a broader array of food types (both invertebrates and plant material, primarily berries) than during the first attempt, which includes only animal food such as arthropods and annelids. We suggest that this difference in breeding strategies between nesting attempts and sexes is in part influenced by marked seasonal variation in food availability.

SummaryAims Despite more than a century of research, spinal paralysis remains untreatable via biological means. A new understanding of spinal cord physiology and the introduction of membrane fusogens have provided new hope that a biological cure may soon become available. However, proof is needed from adequately powered animal studies. Methods and results Two groups of rats (n=9, study group, n=6 controls) were submitted to complete transection of the dorsal cord at T10. The animals were randomized to receive either saline or polyethylene glycol (PEG) in situ. After 4 weeks, the treated group had recovered ambulation vs none in the control group (BBB scores; P=.0145). One control died. All animals were studied with somatosensory-evoked potentials (SSEP) and diffusion tensor imaging (DTI). SSEP recovered postoperatively only in PEG-treated rats. At study end, DTI showed disappearance of the transection gap in the treated animals vs an enduring gap in controls (fractional anisotropy/FA at level: P=.0008). Conclusions We show for the first time in an adequately powered study that the paralysis attendant to a complete transection of the spinal cord can be reversed. This opens the path to a severance-reapposition cure of spinal paralysis, in which the injured segment is excised and the two stumps approximated after vertebrectomy/diskectomies.

BACKGROUND AND OBJECTIVES: To study selective regional binding for tau pathology in vivo, using PET with [(11) C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.METHODS: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [(11) C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region.RESULTS: In comparison to the control group, PSP subjects showed specific uptake of [(11) C]PBB3 in putamen, midbrain, GP, and SN. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. A DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and GP. In SNCA duplication carriers, there was a significant increase of [(11) C] PBB3 binding in GP, putamen, thalamus, ventral striatum, SN, and pedunculopontine nucleus. The MSA case showed increased binding in frontal lobe, GP, midbrain, parietal lobe, putamen, temporal lobe, SN, thalamus, and ventral striatum.CONCLUSIONS: All PSP patients showed increased retention of the tracer in the basal ganglia, as expected. Binding was also present in asymptomatic SNCA duplication carriers and in an MSA case, which are not typically associated with pathological tau deposition. This suggests the possibility that [(11) C]PBB3 binds to alpha-synuclein. © 2017 International Parkinson and Movement Disorder Society. (Less)

A facile and efficient method for the synthesis of benzo[b]pyrido[3,2-f][1,7]phenanthrolines and dipyrido[4,3-b:3′,2′-f][1,7]phenanthrolines has been developed in high yields. Using EtOH as a solvent without any additionally basic catalysts, the three-component reaction of aromatic aldehyde, 1,10-phenanthrolin-5-amine, and dimedone or piperidine-2,4-dione affords two novel classes of fused phentacyclic heterocycles containing both pyridine and phenanthroline moieties.

The application of sequencing technology is shifting from research to clinical laboratories owing to rapid technological developments and substantially reduced costs. However, although thousands of microorganisms are known to infect humans, identification of the etiological agents for many diseases remains challenging as only a small proportion of pathogens are identifiable by the current diagnostic methods. These challenges are compounded by the emergence of new pathogens. Hence, metagenomic next‐generation sequencing (mNGS), an agnostic, unbiased, and comprehensive method for detection, and taxonomic characterization of microorganisms, has become an attractive strategy. Although many studies, and cases reports, have confirmed the success of mNGS in improving the diagnosis, treatment, and tracking of infectious diseases, several hurdles must still be overcome. It is, therefore, imperative that practitioners and clinicians understand both the benefits and limitations of mNGS when applying it to clinical practice. Interestingly, the emerging third‐generation sequencing technologies may partially offset the disadvantages of mNGS. In this review, mainly: a) the history of sequencing technology; b) various NGS technologies, common platforms, and workflows for clinical applications; c) the application of NGS in pathogen identification; d) the global expert consensus on NGS‐related methods in clinical applications; and e) challenges associated with diagnostic metagenomics are described., Sequencing technology is becoming increasingly available in clinic. This review sheds lights on the most commonly used metagenomic next‐generation sequencing (mNGS). History and different platforms, current workflows, and applications of mNGS in pathogens identification, as well as challenges in the diagnostic metagenomics, are discussed. mNGS cannot substitute for traditional methods in the short term, but plays an irreplaceable role in microbiological detection.

An original gadolinium-hybridized plasmonic gold nanocomposite is fabricated to provide an insightful and attractive strategy to overcome both the physiological and pathological barriers of tumor, and increase the transportation and permeability of imaging agents and drugs in tumor interior for achieving high-sensitive multimodal imaging and simultaneously improving the therapeutic efficacy of cancer.

Territoriality is an important male behavioral trait used in mate selection of butterflies, but the factors determining the outcome of territorial contests remain controversial. We studied the foraging and territorial behaviors of males in the Parnassius imperator butterfly. Adult males were selective about nectar sources, but they did not defend nectar flowers. By contrast, they fought over areas of bare rocks because bare rocks were used as lek locations to attract and court receptive females. The ownership of a lek, rather than sex pheromones or wing pigments, played the key role in attracting females. In an owner replacement experiment, the owner of a territory always defeated intruders, indicating that perching order, not relative body size, determined the outcome of territorial contests. Territories are small areas of bare rocks that lack food resources, so intruders do not challenge the ownership of a resident in a location where they can easily find vacant territories. Males that first perch in a territory have an advantage compared to intruders in that they can forage on flowers in the vicinity of the territory. This may help explain why satiated owners always defeated fatigued intruders. Our findings suggest that early perching on bare rock allows male butterflies of P. imperator to occupy a territory, attract receptive females and exclude later-arriving competitors.

In this paper, we obtain the existence of infinitely solutions for a class of nonlocal elliptic systems of (p1(x),⋯,pn(x))-Kirchhoff type. Our main results are new. Our approach are based on general variational principle because of B. Ricceri and the theory of the variable exponent Sobolev spaces. Copyright © 2015 John Wiley & Sons, Ltd.

Prior research has linked the innovative behavior of public sector employees to desirable outcomes, such as improved efficiency and higher public service quality. However, questions regarding the drivers of innovative behavior among employees have received limited attention. This study employs psychological empowerment theory to examine the underlying processes by which entrepreneurial leadership and public service motivation (PSM) shape innovative behavior among civil servants. Using three-wave data from 281 Chinese civil servants and their 59 department heads, entrepreneurial leadership is found to positively influence subordinates’ innovative behavior by enhancing two dimensions of psychological empowerment: meaning and impact. Additionally, PSM was found to influence subordinates’ innovative behavior by enhancing the dimensions of meaning and competence. Our findings suggest that to facilitate innovative behavior amongst employees, public organizations should consider introducing training that encourages leaders to serve as entrepreneurial role models and recruit employees with high levels of PSM.

The newly discovered borospherenes B40 (-/0) and B39 (-) mark the onset of a new class of boron nanostructures. Based on extensive first-principles calculations, we introduce herein two new chiral members to the borospherene family: the cage-like C1 B41 (+) (1) and C2 B42 (2+) (2), both of which are the global minima of the systems with degenerate enantiomers. These chiral borospherene cations are composed of twelve interwoven boron double chains with six hexagonal and heptagonal faces and may be viewed as the cuborenes analogous to cubane (C8 H8 ). Chemical bonding analyses show that there exists a three-center two-electron σ bond on each B3 triangle and twelve multicenter two-electron π bonds over the σ skeleton. Molecular dynamics simulations indicate that C1 B41 (+) (1) fluctuates above 300 K, whereas C2 B42 (2+) (2) remains dynamically stable. The infrared and Raman spectra of these borospherene cations are predicted to facilitate their experimental characterizations.

Magnoflorine, an important aporphine alkaloid in Coptidis Rhizoma, is increasingly attracting research attention because of its pharmacological activities. The in vivo and in vitro metabolism of magnoflorine was investigated by LC LTQ-Orbitrap MS. In vivo samples including rat urine, feces, plasma and bile were collected separately after both oral (50 mg kg−1) and intravenous administration (10 mg kg−1) of magnoflorine, along with in vitro samples prepared by incubating magnoflorine with rat intestinal flora and liver microsome. As a result, 12 metabolites were found in biological samples. Phase I metabolites were identified in all biological samples, while phase II metabolites were mainly detected in urine, plasma and bile. In a pharmacokinetic study, rats were not only dosed with magnoflorine via oral (15, 30 and 60 mg kg−1) and intravenous administration (10 mg kg−1) but also dosed with Coptidis Rhizoma decoction (equivalent to 30 mg kg−1 of magnoflorine) by intragastric administration to investigate the interaction of magnoflorine with the rest of compounds in Coptidis Rhizoma. Studies showed that magnoflorine possessed lower bioavailability and faster absorption and elimination. However, pharmacokinetic parameters altered significantly (p

Background Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Methods Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Results Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Conclusions Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

The present study examines whether participative leadership engenders organizational commitment among Chinese civil servants, and analyzes the mechanisms by which it transmits its effects. Confirmatory factor analysis and structural equation modeling revealed that there was a significant relationship between supervisor-level participative leadership and the affective and normative commitment of subordinates, but no relationship with continuance commitment. Affective trust was identified as the mediator variable underlying the relationship between participative leadership and organizational commitment. We show that participative leadership of supervisors elicits higher levels of trust, and leads subordinates to reciprocate through exhibiting higher levels of organizational commitment. Our study also reveals that Chinese civil servants who accept an unequal distribution of power between supervisors and subordinates typically exhibit lower levels of affective and normative commitment to the organization than those who do not. Our results provide greater support for the deepening of administrative reforms and the dissemination of participative leadership practices in China’s new civil service system.

Sample preparation is always the major bottleneck in analytical chemistry for the determination of pesticide residues. Different sample preparation methods have been proposed due to the wide variety of pesticides used and the inherent complexity of the matrices. In this study, different sample preparation methods including SPE, matrix solid-phase dispersion, the quick, easy, cheap, efficient, rugged, and safe method, and a one-step completion method were compared and evaluated for extracting pesticides from lotus seeds. Analysis was carried out using GC with electron-capture detection. The results showed that good recoveries for tested pesticides were obtained by using Florisil in the four methods, and the extraction efficiency of the one-step completion method was superior to the other three methods. The one-step completion method was confirmed to have good linearity, reproducibility, stability, and recovery for the detection of 36 pesticides in lotus seed samples. The data collected from this study are expected to prove useful in regulating the concentration of the residues in lotus seeds, as well as in protecting human health from the hazards posed by these residues.

What's known on the subject? and What does the study add? In the urinary bladder, histological studies suggest a network of functionally connected interstitial cells of Cajal (ICCs) are located between the urothelium and sensory nerve endings, which might transfer signals directly between them. Purinergic P2X3 receptors may play roles in the micturition reflex pathway, and its expression profiles in ICCs could be altered in urinary bladder dysfunction. The present experiments showed a novel time-dependent P2X3 receptor up-regulation in ICCs in an experimental rat model of partial bladder outlet obstruction. Objective To investigate the expression and electrophysiological characteristics of purinergic P2X3 receptors in interstitial cells of Cajal (ICCs) at different time points after partial bladder outlet obstruction (PBOO) in rats. Materials and Methods In all, 48 female Sprague-Dawley rats were randomly divided into four groups: 4, 6 and 8 week PBOO groups and sham-operated controls. At 4 weeks after surgery, cystometry was performed to investigate bladder function in vivo. Subsequently, the rats were humanely killed at 4, 6 or 8 weeks and the bladders were harvested for measurements. P2X3 expression in ICCs of bladder was investigated by immunofluorescent staining. The level of P2X3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Inward currents in corresponding ICCs after PBOO were investigated electrophysiologically. Results Cystometrography showed a valid increase in maximum detrusor pressure in rats subjected to PBOO. The bladder weight in the PBOO group was significantly higher than that in the control group. In contrast to sham rats, there was a significant increase in the intensity of P2X3 staining in the ICCs in all PBOO groups. C-kit labelled isolated ICCs were strongly stained with the P2X3 antibody. RT-PCR showed that the expression of P2X3 mRNA was significantly up-regulated at 4, 6 and 8 weeks in the ICCs from the PBOO rats. In the ICCs, the mean peak amplitude of inward currents was significantly increased in the PBOO groups compared with the control group. Conclusions The expression of P2X3 receptors showed a time dependent up-regulation in the ICCs of the bladder in rats with PBOO. PBOO induced the potentiation of P2X3 receptors function, as evidenced by α, β-methylene ATP-enhanced inward currents in the ICCs of the rat bladder.