Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.

Domestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.

Plasma metabolomic signature of healthy lifestyle, structural brain reserve and risk of dementia.

Although the association between healthy lifestyle and dementia risk has been documented, the relationship between a metabolic signature indicative of healthy lifestyle and dementia risk and the mediating role of structural brain impairment remain unknown. We retrieved 136 628 dementia-free participants from UK Biobank. Elastic net regression was used to obtain a metabolic signature that represented lifestyle behaviours. Cox proportional hazard models were fitted to explore the associations of lifestyle-associated metabolic signature with incident dementia. Causal associations between identified metabolites and dementia were investigated using Mendelian randomization. Mediation analysis was also conducted to uncover the potential mechanisms involving 19 imaging-derived phenotypes (brain volume, grey matter volume, white matter volume and regional grey matter volumes). During a follow-up of 12.55 years, 1783 incident cases of all-cause dementia were identified, including 725 cases of Alzheimer's dementia and 418 cases of vascular dementia. We identified 83 metabolites that could represent healthy lifestyle behaviours using elastic net regression. The metabolic signature was associated with a lower dementia risk, and for each standard deviation increment in metabolic signature, the hazard ratio was 0.89 [95% confidence interval (CI): 0.85, 0.93] for all-cause dementia, 0.95 (95% CI: 0.88, 1.03) for Alzheimer's dementia and 0.84 (95% CI: 0.77, 0.91) for vascular dementia. Mendelian randomization revealed potential causal associations between the identified metabolites and risk of dementia. In addition, the specific structural brain reserve, including the hippocampus, grey matter in the hippocampus, parahippocampal gyrus and middle temporal gyrus, were detected to mediate the effects of metabolic signature on dementia risk (mediated proportion ranging from 6.21% to 11.98%). The metabolic signature associated with a healthy lifestyle is inversely associated with dementia risk, and greater structural brain reserve plays an important role in mediating this relationship. These findings have significant implications for understanding the intricate connections between lifestyle, metabolism and brain health.

High-Performance Aqueous Calcium Ion Batteries Enabled by Zn Metal Anodes with Stable Ion-Conducting Interphases.

Aqueous calcium ion batteries, promising for energy storage, are still challenged by very limited anode choices. Although a Zn metal anode is popular in aqueous batteries, interface instability due to incessant corrosion and severe Zn dendrites hinders its development. Here, an interphase layer with densely packed nanocrystals of Ca3(CO3)2(OH)2·1.5H2O and ZnF2, and amorphous organic species, is demonstrated for a Zn metal anode with 1 M calcium trifluoromethyl sulfonate aqueous electrolyte. The hybrid interface fully avoids direct Zn-H2O contact, maintains fast ion conductivity, and effectively prevents corrosion and dendrite growth. Therefore, the symmetric cell stably lasts for 1600 h at 0.5 mA cm-2 and 2.5 mAh cm-2, far superior to 150 h for the control cell. Furthermore, the device maintains 80% capacity retention after 700 cycles at 1 A g-1, outperforming 13% retention after 200 cycles for the control device. This work indicates that interface and interphase engineering is also crucial for aqueous batteries.

Genome-wide association studies of body size traits in Tibetan sheep.

BACKGROUND: Elucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai's animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province's population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep. RESULT: In this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8. CONCLUSION: By genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.

Unusual Janus Bi2TeSe2 Topological Insulators Displaying Second-Harmonic Generation, Linear-in-Temperature Resistivity, and Weak Antilocalization.

Well-established knowledge about inversion-symmetric Bi2TexSe3-x topological insulators characterizes the promising new-generation quantum device. Noticeably, the inversion asymmetric phase containing different surface electronic structures may create an extra topological phenomenon pointing to a new device paradigm. Herein, Janus Bi2TeSe2 single-crystal nanosheets with an unconventional stacking sequence of Se-Bi-Se-Bi-Te are realized via chemical vapor deposition growth, which is clarified by atomically resolved AC-STEM and elemental mapping. An obvious polarization-dependent second-harmonic generation with a representative 6-fold rotational symmetry is detected due to the broken out-of-plane mirror symmetry in this system. Low-temperature transport measurements display a strange metal-like linear-in-temperature resistivity. Anomalous conductance peaks under low magnetic fields induced by the weak antilocalization effect of topological surface states and the two-dimensional transport-dominated anisotropic magnetoresistance are revealed. These findings correlate the Janus Bi2TeSe2 phase with emerging physics topics, which would inspire fresh thoughts in well-developed Bi3TexSe3-x topological insulators and open up opportunities for exploring hybrid nonlinear optoelectronic topological devices.

Characterizing metabolomic signatures related to coffee and tea consumption and their association with incidence and dynamic progression of type 2 diabetes: A multi-state analysis.

Our study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.

Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study.

BACKGROUND & AIMS: To identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We utilized data from the UK Biobank Cohort. Annual mean concentrations of PM2.5, PM10, NO2 and NOx were assessed for each participant using bilinear interpolation. The Elastic Net regression model was used to identify metabolites associated with four air pollutants and to construct metabolic signatures, respectively. Associations between air pollutants, metabolic signatures and MASLD were analyzed using Cox models. Mendelian randomization (MR) analysis was used to examine potential causality. Mediation analysis was employed to examine the role of metabolic signatures in the association between air pollutants and MASLD. RESULTS: A total of 244,842 participants from the UK Biobank were included in this analysis. We identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM2.5, PM10, NO2, and NOx, respectively. Metabolic signatures were associated with risk of MASLD, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) were 1.10 (1.06, 1.14), 1.06 (1.02, 1.10), 1.24 (1.20, 1.29) and 1.14 (1.10, 1.19). The four pollutants were associated with increased risk of MASLD, with HRs (95% CIs) of 1.03 (1.01, 1.05), 1.02 (1.01, 1.04), 1.01 (1.01, 1.02) and 1.01 (1.00, 1.01). MR analysis indicated an association between PM2.5, NO2 and NOx-related metabolic signatures and MASLD. Metabolic signatures mediated the association of PM2.5, PM10, NO2 and NOx with MASLD. CONCLUSION: There may be association between PM2.5, PM10, NO2 and NOx-related metabolic signatures and MASLD, and metabolic signatures mediate the increase of PM2.5, PM10, NO2 and NOx in the risk of MASLD. IMPACT AND IMPLICATIONS: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), however, the mechanism by which air pollution affects MASLD remains unclear. Our study used integrated serological metabolic data of 251 metabolites from a large-scale cohort study to demonstrate that metabolic signatures play a crucial role in the elevated risk of MASLD caused by air pollution. These results are relevant to patients and policymakers because they suggest that air pollution-related metabolic signatures are not only potentially associated with MASLD but also involved in mediating the process by which PM2.5, PM10, NO2, and NOx increase the risk of MASLD. Focusing on changes in air pollution-related metabolic signatures may offer a new perspective for preventing air pollution-induced MASLD and serve as protective measures to address this emerging public health challenge.

PFC/M1 activation and excitability: a longitudinal cohort study on fatigue symptoms in healthcare workers post-COVID-19.

BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.

A model of hybrid speciation process drawn from three new poplar species originating from distant hybridization between sections.

Although numerous studies have been conducted on hybrid speciation, our understanding of this process remains limited. Through an 18-year systematic investigation of all taxa of Populus on the Qinghai-Tibet Plateau, we discovered three new taxa with clear characteristics of sect. Leucoides. Further evidence was gathered from morphology, whole-genome bioinformatics, biogeography, and breeding to demonstrate synthetically that they all originated from distant hybridization between sect. Leucoides and sect. Tacamahaca. P. gonggaensis originated from the hybridization of P. lasiocarpa with P. cathayana, P. butuoensis from the hybridization of P. wilsonii with P. szechuanica, and P. dafengensis from the hybridization of P. lasiocarpa with P. szechuanica. Due to heterosis, the three hybrid taxa possess greater ecological adaptability than their ancestral species. We propose a hybrid speciation process model that incorporates orthogonal, reverse, and backcrossing events. This model can adequately explain some crucial evolutionary concerns, such as the nuclear-cytoplasmic conflict on phylogeny and the extinction of ancestral species within the distribution range of hybrid species.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Magnetic materials as adsorbents for the pre-concentration and separation of active ingredients from herbal medicine.

Herbal medicine (HM) is crucial in disease management and contains complex compounds with few active pharmacological ingredients, presenting challenges in quality control of raw materials and formulations. Effective separation, identification, and analysis of active components are vital for HM efficacy. Traditional methods like liquid-liquid extraction and solid-phase extraction are time-consuming and environmentally concerning, with limitations such as sorbent issues, pressure, and clogging. Magnetic solid-phase extraction uses magnetic sorbents for targeted analyte separation and enrichment, offering rapid, pressure-free separation. However, inorganic magnetic particles' aggregation and oxidation, as well as lack of selectivity, have led to the use of various coatings and modifications to enhance specificity and selectivity for complex herbal samples. This review delves into magnetic composites in HM pretreatment, specifically focusing on encapsulated or modified magnetic nanoparticles and materials like silica, ionic liquids, graphene family derivatives, carbon nanotubes, metal-organic frameworks, covalent organic frameworks, and molecularly imprinted polymers.

To Accelerate the Process of Brain Death Determination in China Through the Strategy and Practice of Establishing Demonstration Hospitals.

BACKGROUND: Our objective was to explore whether a brain death determination (BDD) strategy with demonstration hospitals can accelerate the process of BDD in China. METHODS: We proposed the construction standards for the BDD quality control demonstration hospitals (BDDHs). The quality and quantity of BDD cases were then analyzed. RESULTS: A total of 107 BDDHs were established from 2013 to 2022 covering 29 provinces, autonomous regions, and municipalities under jurisdiction of the central government of the Chinese mainland (except Qinghai and Tibet). A total of 1,948 professional and technical personnel from these 107 BDDHs received training in BDD, 107 quality control personnel were trained in the quality control management of BDD, and 1,293 instruments for electroencephalography, short-latency somatosensory evoked potential recordings, and transcranial Doppler imaging were provided for BDD. A total of 6,735 BDD cases were submitted to the quality control center. Among the nine quality control indicators for BDD in these cases, the implementation rate, completion rate, and coincidence rate of apnea testing increased the most, reaching 99%. CONCLUSIONS: The strategy of constructing BDDHs to promote BDD is feasible and reliable. Ensuring quality and quantity is a fundamental element for the rapid and orderly popularization of BDD in China.

Nonsaturating Linear Magnetoresistance Manifesting Two-Dimensional Transport in Wet-Chemical Patternable Bi2O2Te Thin Films.

Two-dimensional (2D) materials with exotic transport behaviors have attracted extensive interest in microelectronics and condensed matter physics, while scaled-up 2D thin films compatible with the efficient wet-chemical etching process represent realistic advancement toward new-generation integrated functional devices. Here, thickness-controllable growth and chemical patterning of high-quality Bi2O2Te continuous films are demonstrated. Noticeably, except for an ultrahigh mobility (∼45074 cm2 V-1 s-1 at 2 K) and obvious Shubnikov-de Hass quantum oscillations, a 2D transport channel and large linear magnetoresistance are revealed in the patterned Bi2O2Te films. Investigation implies that the linear magnetoresistance correlates with the inhomogeneity described by P. B. Littlewood's theory and EMT-RRN theory developed recently. These results not only reveal the nonsaturating linear magnetoresistance in high-quality Bi2O2Te but shed light on understanding the corresponding physical origin of linear magnetoresistance in 2D high-mobility semiconductors and providing a pathway for the potential application in multifunctional electronic devices.

Development and validation of a rating scale for barriers to and facilitators of nurses' participation intentions in "Internet + Nursing Service".

BACKGROUND: Given increases in China's aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, "Internet + Nursing Services" have received more attention. Thus, exploring the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and utilizing internet technology to increase the supply of nursing services has become a key issue. OBJECTIVE: This study aimed to develop a scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and to test the validity and reliability of the scale. METHODS: A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. RESULTS: The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach's α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. CONCLUSION: The scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" has good reliability and validity, and provides a reference for evaluating nurses' willingness to participate in "Internet + Nursing Services".

Physiological, metabolomic, and transcriptomic reveal metabolic pathway alterations in Gymnocypris przewalskii due to cold exposure.

Teleost fish have evolved various adaptations that allow them to tolerate cold water conditions. However, the underlying mechanism of this adaptation is poorly understood in Tibetan Plateau fish. RNA-seq combined with liquid chromatography‒mass spectrometry (LC‒MS/MS) metabolomics was used to investigate the physiological responses of a Tibetan Plateau-specific teleost, Gymnocypris przewalskii, under cold conditions. The 8-month G. przewalskii juvenile fish were exposed to cold (4 ℃, cold acclimation, CA) and warm (17 ℃, normal temperature, NT) temperature water for 15 days. Then, the transcript profiles of eight tissues, including the brain, gill, heart, intestine, hepatopancreas, kidney, muscle, and skin, were evaluated by transcriptome sequencing. The metabolites of the intestine, hepatopancreas, and muscle were identified by LC‒MS/MS. A total of 5,745 differentially expressed genes (DEGs) were obtained in the CA group. The key DEGs were annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The DEGs from the eight tissues were significantly enriched in spliceosome pathways, indicating that activated alternative splicing is a critical biological process that occurs in the tissues to help fish cope with cold stress. Additionally, 82, 97, and 66 differentially expressed metabolites were identified in the intestine, hepatopancreas, and muscle, respectively. Glutathione metabolism was the only overlapping significant pathway between the transcriptome and metabolome analyses in these three tissues, indicating that an activated antioxidative process was triggered during cold stress. In combination with the multitissue transcriptome and metabolome, we established a physiology-gene‒metabolite interaction network related to energy metabolism during cold stress and found that gluconeogenesis and long-chain fatty acid metabolism played critical roles in glucose homeostasis and energy supply.

Two-Dimensional Superconductivity in Air-Stable Single-Crystal Few-Layer Bi3O2S3.

The progress of unconventional superconductors at the two-dimensional (2D) limit has inspired much interest. Recently, a new superconducting system was discovered in the semimetallic ternary Bi-O-S family. However, pure-phase crystals are difficult to synthesize because of the complicated stacking sequence of multiple charged layers and similar formation kinetics among ternary polytypes, leaving several fundamental issues regarding the structure-superconductivity correlation unresolved. Herein, 2D single-crystal ultrathin Bi3O2S3 nanosheets are prepared by using low-pressure chemical vapor deposition, and their atomic arrangement is clarified. Magnetotransport measurements indicate a superconducting transition at ∼6.1 K that is thickness-independent. The transport results demonstrate 2D superconducting characteristics, such as the Berezinskii-Kosterlitz-Thouless transition, and strong anisotropy with magnetic field orientations following the 2D Tinkham formula. The difference from superconductivity of powder is demonstrated from the perspective of their corresponding microstructures. These results corroborate the superconducting behavior of Bi3O2S3, providing fresh insights into the search for other bismuth oxychalcogenides and derivative BiS2-based analogues at the 2D limit.

Effects of the SPI/lncRNA NEAT1 Axis on Functions of Trophoblast and Decidual Cells in Patients with Recurrent Miscarriage.

Recurrent miscarriage (RM) is a frustrating and complex pregnancy disorder and long noncoding RNAs (lncRNAs) modulate susceptibility to RM. This study expounded on the role of specificity protein 1 (SP1) in functions of chorionic trophoblast and decidual cells via regulating lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1). Chorionic villus tissues and decidual tissues of RM patients and normal pregnant women were collected. Real-time quantitative polymerase chain reaction and Western blotting revealed that SP1 and NEAT1 were downregulated in trophoblast and decidual tissues of RM patients, and the Pearson correlation analysis detected that they were positively correlated in expression level. Chorionic trophoblast and decidual cells of RM patients were isolated and intervened by vectors over-expressing SP1 or NEAT1 siRNAs. Thereafter, the cell counting kit-8, Transwell, flow cytometry assays detected that SP1 overexpression accelerated trophoblast cell proliferation, invasion, and migration, meanwhile, enhancing decidual cell proliferation while repressed apoptosis. Next, the dual-luciferase and Chromatin immunoprecipitation assays showed that SP1 bound to the NEAT1 promoter region and further activated NEAT1 transcription. Silencing NEAT1 reversed the efforts of SP1 overexpression on the functions of trophoblast and decidual cells. Overall, SP1 activated NEAT1 transcription, accelerating trophoblast cell proliferation, invasion, and migration and mitigating decidual cell apoptosis.

Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study.

BACKGROUND: No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. METHODS: We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. RESULTS: During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µg/m3 increase of 1.31 (1.22 to 1.42) and 1.27 (1.01 to 1.57) for transitions from healthy to incident chronic lung disease and from incident chronic lung disease to chronic lung multimorbidity, and 1.32 (1.21 to 1.45), 1.24 (1.01 to 1.53) and 1.91 (1.14 to 3.20) for mortality risk from healthy, incident chronic lung disease and chronic lung multimorbidity, respectively. CONCLUSION: Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Poly(ethylene oxide) Concentration Gradient-Based Microfluidic Isolation of Circulating Tumor Cells.

Circulating tumor cells (CTCs) have emerged as promising circulating biomarkers for non-invasive cancer diagnosis and management. Isolation and detection of CTCs in clinical samples are challenging due to the extreme rarity and high heterogeneity of CTCs. Here, we describe a poly(ethylene oxide) (PEO) concentration gradient-based microfluidic method for rapid, label-free, highly efficient isolation of CTCs directly from whole blood samples. Stable concentration gradients of PEO were formed within the microchannel by co-injecting the side fluid (blood sample spiked with 0.025% PEO) and center fluid (0.075% PEO solution). The competition between the elastic lift force and the inertial lift force enabled size-based separation of large CTCs and small blood cells based on their distinct migration patterns. The microfluidic device could process 1 mL of blood sample in 30 min, with a separation efficiency of >90% and an enrichment ratio of >700 for tumor cells. The isolated CTCs from blood samples were enumerated by immunofluorescence staining, allowing for discrimination of breast cancer patients from healthy donors with an accuracy of 84.2%. The concentration gradient-based microfluidic separation provides a powerful tool for label-free isolation of CTCs for a wide range of clinical applications.