Search

Multivalent presentation of antigens using nanoparticles (NPs) as a platform is an effective strategy to enhance the immunogenicity of subunit vaccines and thus induce a high level of organismal immune response. Our previous results showed that pre-existing porcine circovirus type 2 (PCV2) antibodies could increase the antibody levels of nanoparticle vaccines carried in PCV2 VLPs. Here, we have established a generalized nanoantigen display platform, Cap-Cat virus-like particles (VLPs). By combining PCV2 VLPs with the modular linker element SpyTag003/SpyCatcher003 system, four porcine-derived viral protective antigens with different sizes and multimeric structures: the PRRSV B-cell epitope, the PEDV COE monomer, the CSFV E2 dimer, and the SIV HA trimer were efficiently demonstrated to elicit a strong immune response in mice. Crucially, the modification of antigens by the Cap-Cat VLPs platform enhanced the Th2 response and improved the Th1 response. The use of the platform demonstrates that HA antigen protects against lethal attacks by influenza viruses and reduces viral load in the lungs. We have demonstrated that the Cap-Cat VLPs platform demonstrates that antigens enhance the immune response by improving the processes of DC uptake, transport, lymph node (LN) localization, and immune cell activation. This “plug-and-display” assembly strategy facilitates the use of the Cap-Cat VLPs nanoantigen display platform for more applications and thus facilitates the development of more efficient, general-purpose porcine subunit vaccines.

ABSTRACTThe present study aims to reveal characteristics of the diaphragm pump applied in transporting the mixture of liquid and solid particles. The computational fluid dynamics (CFD) technique was used in combination with the six degree of freedom (SDOF) method to simulate the solid-liquid two-phase flow in the diaphragm pump. The zero-gap overlapping grid technique was employed to treat unsteady gap flows near the two valves. Effects of particle size and the reciprocating frequency of the plunger were investigated. The results indicate that solid particles pass smoothly through the diaphragm pump. When particle size increases from 2.0 mm to 3.0 mm, the solid volume fraction (SVF) in the pump chamber increases. When the reciprocating frequency of the plunger increases from 150 to 250 cycles per minute, the SVF increases and then decreases. When the reciprocating frequency of the plunger increases, the performance of the diaphragm pump declines, whereas the distribution of particles in the pump chamber is gradually uniformized due to the disturbance of the reversed flow from the pump outlet.

The importance of carbonate weathering carbon sinks (CCSs) is almost equal to that of vegetation photosynthesis in the global carbon cycle. However, CCSs have become controversial in formulating carbon neutral policies to deal with global climate problems in various countries, since the carbonate dissolution is reversible. In order to address these controversies, we reviewed recent advances in understanding CCSs and examined the outstanding controversies surrounding them. We have analyzed the five controversies, revealing the existence of CCSs, quantifying their magnitude, clarifying their spatiotemporal pattern, and documenting how they have increased and how they evolved under the background of global change. By addressing these five controversies, we help to bring clarity to the role of CCSs in the carbon cycle of global terrestrial ecosystems.

Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccine-induced immunity and prolong the time-effectiveness, we design a priming–boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&−)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&−) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&−), BNV(−) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.

Lung sounds can be translated into acoustic imaging as an alternative to standard imaging to assess lung function frequently for improved therapy efficiency. This study proposes a comprehensive acoustic lung imaging system translated from acquired lung sounds for continual and reliable lung function assessment in response to the growing clinical interest in frequent lung function assessment. The proposed system comprises subsystems, such as data acquisition, signal processing, and imaging algorithm. This study demonstrated the design and implementation of a robust lung sound acquisition and imaging system using microelectromechanical microphones that reduce external noise contamination through redesigned hardware and dynamic signal processing. Regarding lung signal acquisition, the proposed system accomplished better root mean square error (RMSE) by around 0.15 and signal-to-noise ratio (SNR) by about 7 dB compared to commercial digital stethoscopes. RMSE and SNR reflect the accuracy in capturing desired signals and robustness-to-noise contamination and are used to quantitatively compare the system data acquisition to the commercially available acoustic and electronic devices in a noisy setting. The proposed system’s sensor position is neutral when representing lung signals, with a signal power loss ratio of around 5 dB compared to 10 dB from digital stethoscopes, in terms of the sensor area sensing sensitivity power spectrum mapping. The proposed system obtains about 7%–12% of more accurate detection of the actual nidus length than digital stethoscopes through imaging translated from acquired lung signals. Additionally, the detected airway obstruction results agree closely (91%) with airway remodeling studies.

ABSTRACTGraft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens1. Graft-versus-host disease is considered a serious complication of hematopoietic stem cell transplantation. The skin, oral cavity and lungs are commonly affected organs. Among these complications bronchiolitis obliterans syndrome is a serious complication, which even can be life-threatening. Therefore, this research aims to do a clinical observation on the safety and efficacy of umbilical cord mesenchymal stem cells in the treatment of bronchiolitis obliterans after allogeneic haematopoietic stem cell transplantation. Fifteen patients were included in this study, who received allogeneic hematopoietic stem cell transplantation. Among these patients, both of them were treated with azithromycin, montelukast, glucocorticoid and pirfenidone. Two of them did not receive second line anti-rejection treatment due to economic reasons, and three of them were treated with mesenchymal stem cells. These bronchiolitis obliterans syndrome-related symptoms such as shortness of breath, chest tightness and wheezing have improved. Two of them died due to bronchiolitis obliterans syndrome related complications such as respiratory failure. Two of them not only improve the symptoms but also increased the FEV1/FVC, who were treated with mesenchymal stem cells. The comprehensive treatment regimen containing imatinib and ruxolitinib is safe and effective and mesenchymal stem cell is a promising treatment option to improve the prognosis of post-HSCT BOS.

The fabrication of scalable all-perovskite tandem solar cells is considered an attractive route to commercialize perovskite photovoltaic modules1. However, the certified efficiency of 1-cm2-scale all-perovskite tandem solar cells lags behind their small-area (approximately 0.05-cm2) counterparts2,3. This performance deficit originates from inhomogeneity in wide-bandgap (WBG) perovskite solar cells (PSCs) at a large scale. The inhomogeneity is known to be introduced at the bottom interface and within the perovskite bulk itself4,5. Here we uncover another crucial source for the inhomogeneity—the top interface formed during the deposition of the electron transport layer (ETL; C60). Meanwhile, the poor ETL interface is also a notable limitation of device performance. We address this issue by introducing a mixture of 4-fluorophenethylamine (F-PEA) and 4-trifluoromethyl-phenylammonium (CF3-PA) to create a tailored 2D perovskite layer (TTDL), in which F-PEA forms a 2D perovskite at the surface, reducing contact losses and inhomogeneity, and CF3-PA enhances charge extraction and transport. As a result, we demonstrate a high open-circuit voltage (Voc) of 1.35 V and an efficiency of 20.5% in 1.77-eV WBG PSCs at a square-centimetre scale. By stacking with a narrow-bandgap (NBG) perovskite subcell, we report 1.05-cm2all-perovskite tandem cells delivering 28.5% (certified 28.2%) efficiency, the highest reported so far. Our work showcases the importance of treating the top perovskite/ETL contact for upscaling PSCs.

Two-terminal monolithic perovskite/silicon tandem solar cells demonstrate huge advantages in power conversion efficiency compared with their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a substantial challenge for perovskite/silicon tandem cells3,4. By exploiting the nanoscale discretely distributed lithium fluoride ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer-intertwined passivation strategy that combines efficient electron extraction with further suppression of non-radiative recombination. We constructed perovskite/silicon tandem devices on a double-textured Czochralski-based silicon heterojunction cell, which featured a mildly textured front surface and a heavily textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite/silicon tandem achieved an independently certified stabilized power conversion efficiency of 33.89%, accompanied by an impressive fill factor of 83.0% and an open-circuit voltage of nearly 1.97 V. To the best of our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley–Queisser limit of 33.7%.

Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO2concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes (CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature (MAT), precipitation (MAP), evapotranspiration (ET), soil water (SM), and the normalized difference vegetation index (NDVI) to the CCSF. The results revealed that (1) China’s CCSF was 22.76 t CO2km−2yr−1, which was higher than the global average (15.771CO2km−2yr−1). The total carbonate rock chemical weathering carbon sink (CCS) was 4772.67×104t CO2, contributing 14.91% of the global CCS through a carbonate rock area of 252.98×104km−2. (2) China’s CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and 7.27 t CO2km−2yr−1in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively. (3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO2km−2yr−1. (4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance and provide a reference for the diagnosis and gap analysis of the national and global carbon neutrality capacities.

Intracellular pressure regulates cell physiological activities and impacts cell micromanipulation results. The measurement of intracellular pressure may reveal the mechanism of these cell physiological activities and improve the micromanipulation accuracy for cells. Current intracellular pressure measurement methods usually rely on specialized and expensive devices or have significant cytotoxicities on cells. In this article, a simple robotic intracellular measurement method based on an improved balance pressure model is developed on the traditional cell manipulation system setup. First, an improved balance pressure model is proposed to calculate the intracellular pressure. Then, a traditional glass micropipette is used as a probe to penetrate the cell membrane to measure intracellular pressure. After cell membrane penetration, the key parameters of the improved balance pressure model including the cell deformation and the moving distance of the gas–liquid interface (GLI) inside the micropipette are measured in time to calculate the intracellular pressure. The experimental results on porcine oocytes demonstrate that the proposed method has an 80% success rate at an average measurement speed of 12 s/cell. Furthermore, no intracellular pressure leaking was tested during the measurement process, guaranteeing measurement accuracy. Furthermore, an 87.5% survival rate of operated oocytes was obtained after the measurement, proving limited damage to cell viability. Our method is highly expected to be applied in biological applications requiring in situ measurement of intracellular pressure.

Bio-based polymers have been widely investigated as sustainable low dielectric (low-k) materials in past decades. Nevertheless, a few of the polymers with excellent comprehensive properties have been achieved to satisfy the requirements of high-frequency communication application. In this paper, two fluorinated monomers (BCB-Fand 2BCB-F) have been designed and successfully prepared from biomass anethole. The thermal-cross-linkable benzocyclobutene and polyfluorobenzene groups were introduced in order to obtain low-kpolymers with good comprehensive properties. A control monomer C1was prepared from the estragole, the isomer of anethole, to study intensively the effect of structures on properties. Among the thermally cured polymers, cured BCB-Fwith higher fluoride content shows a comparable dielectric constant (Dk) of 2.62 and lower dielectric loss (Df) of 1.31 × 10–3at a frequency of 10 GHz, as well as better hydrophobic properties with a water uptake of 0.18%. Such good hydrophobic properties enable it to maintain the good dielectric properties even after being soaked in boiling water for 96 h. Cured 2BCB-Fwith bifunctional benzocyclobutene groups displays excellent heat resistance with a high glass transition temperature (Tg) of 408 °C and a low coefficient of thermal expansion (CTE) of 52 ppm/°C in the temperature range 30–300 °C. Cured 2BCB-Falso shows good dielectric properties with a Dkof 2.61 and a Dfof 2.60 × 10–3at a frequency of 10 GHz. The good comprehensive properties reveal that the anethole-based polymers are suitable candidates as matrix or encapsulation resins for application in electronics and microelectric fields.

ABSTRACTThis study explores the relationship between signing auditors’ experience and client investment efficiency in the Chinese stock market. After controlling for firm-level, audit firm-level, and other individual characteristics, results show that it is signing auditors’ industry experience, rather than total experience, that significantly restrains client investment inefficiency, including over- and under-investment. This means that industry-specific experience may be the important experience affecting client investment behavior. The mechanism test results also show that experienced auditors can enhance client investment efficiency not only by playing an information role, through which they reduce over- and under-investment, but also partly through a financing channel to mitigate under-investment and a monitoring channel to restrict over-investment, respectively. Further analyses suggest that the effect of signing auditors’ industry experience on client investment efficiency is more pronounced for firms audited by large audit firms, those audited by expertise audit firms, and those located in the region with higher level of marketization. Overall, this study provides evidence related to the economic consequences of auditor experience at the individual level, thus extending the related literature.

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a β-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous β-TCP scaffold were revealed and quantified through an in vivomodel that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the β-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the β-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

To investigate the association between false lumen (FL) dependency of segmental arteries (SAs) at T9-L3 levels and the risk of spinal cord injury (SCI) following total arch replacement and frozen elephant trunk (FET) implantation in the setting of acute DeBakey type I aortic dissection (AAD).

The adsorption properties of Pb2+aqueous solution were studied by means of laboratory-prepared composite particles from steel slag (called SS) and manganese slag (called MS). The effects of the mixing ratio, experimental temperature and adsorption time of the particles on Pb2+were investigated. The isothermal adsorption model of Pb2+and the characterization results were also discussed. Results showed that temperature had little influence on the adsorption process of Pb2+. In the initial solution with Pb2+concentration of 500 mg/L, the best adsorption effect could be achieved when the dosage of particles was 1.0 g. The Pb2+removal efficiency was high when the stirring speed was in the range of 100–300 rpm and the initial solution pH was in the range of 7–9 in the adsorption system. The initial concentration with adsorption equilibrium time of 25 min was 300 mg/L. The adsorption process of the particles fits the Langmuir ISO-temperature model. The maximum saturated adsorption value was 69.93 mg/g.

There are a lot of factors affecting the oxidation resistance of Al2O3-SiC-C castables. The density of the castables plays a key role and influences the Al2O3-SiC-C castables’ physical properties, oxidation resistance, thermal shock resistance, and corrosion resistance. The aim of this work is to use spodumene as an additive to improve the oxidation resistance of the Al2O3-SiC-C castables. The results showed that at high-temperature, solid phases of spodumene transformed into liquid phases, which filled the pores in the Al2O3-SiC-C matrix. Therefore, the silicon carbide, carbon source, and micro silicon in the matrix were protected from oxidation, which promoted the generation of the silicon carbide and mullite whiskers in the matrix during sintering processes. In addition, the mechanical strength, thermal shock resistance, oxidation resistance, and corrosion resistance of specimens were improved with an increase in the content of spodumene. When the content of spodumene reached 2.0 wt.%, the specimens exhibited excellent properties. However, due to the volume expansion of the α-spodumene phase transformation, with a further increase in the content of spodumene, the properties of specimens degraded sharply. Therefore, an optimum content ~ 2.0 wt.% of spodumene was regarded as an improvement agent additive in the Al2O3-SiC-C castables system.

Fiberglass porous ceramics were prepared via a foam-gelcasting method. The relationship between the rheology of the slurries and the structure of the specimens was investigated. The results show that when the content of the dispersant was 0.25 wt %, the slurries exhibit excellent fluidity. The thixotropic behavior of the slurries was strongly influenced by the content of the foam stabilizer agent and solid content. Furthermore, as the fluidity of the foaming slurries increased, the size of the pores increased. At the same time, the thickness of the pore walls decreased gradually. In addition, promoting the uniform distribution of the pore size by improving the thixotropic behavior of the foaming slurries was beneficial. The optimal foaming slurry was composed of 65 wt % fiberglass, 0.25 wt % dispersant, and 0.1 wt % foam stabilizer agent. After calcination at 750 °C, fiberglass porous ceramics with 78.3% porosity, 2.2 MPa compressive strength, and 0.11 W m–1K–1thermal conductivity were obtained.

We retrospectively collected drug susceptibility data of Klebsiella pneumoniaefrom six tertiary hospitals in Shaoxing City in 2019 and performed a comparative analysis of drug resistance among different hospitals, sexes, ages, and specimens. In total, 1954 strains were identified. The antibiotic resistance rate varied from 4.42% to 36.18%. Most K. pneumoniaewere still susceptible to carbapenems and tigecycline, with resistance rates of less than 10%. Drug resistance was relatively mild in Shaoxing Traditional Chinese Medicine Hospital and Shaoxing Maternal and Children Health Hospital, but most severe in Affiliated Hospital of Shaoxing University. Specimens were primarily obtained from elderly and male patients, and the resistance rate increased with age. The specimens were mostly collected from the respiratory and urinary tracts. No carbapenem-resistant strains were collected in 112 isolates from patients under 20 years of age. The ratio of carbapenem-resistant K. pneumoniaeisolates was highest in blood-isolated strains (23.86%), and that of extended-spectrum beta-lactamase positive strains was highest in non-blood-sterile body fluids (37.37%). The resistance spectrum of K. pneumoniaevaried between hospitals in the same area. Elderly and male patients, non-sterile body fluids, and blood source strains should be seriously considered in empirical treatment.HighlightsPrevention and control should be strengthened in hospitals with high rate of drug resistance.Strengthen screening of drug-resistant bacteria in specific populations.Transferred patients should be alerted to the bacterial drug resistance status.

Tetrahydroxy stilbene glucoside (TSG) is a bioactive ingredient with powerful anti-inflammatory and neuroprotective properties. However, the detailed mechanisms concerning the neuroprotective effect of TSG are not fully understood. This study aims to address the molecular mechanism involved in the protective effects of TSG on murine ischemic stroke. We found that TSG meliorated the phenotypes of ischemic stroke in vivo, which was correlated with the increased percentage of infiltrated M2 macrophages in brain after stroke. Mechanistically, TSG regulated macrophage polarization by significantly downregulating the transcriptional levels of M1 marker genes (iNOS and IL-1β) but upregulating that of the M2 marker genes (arg-1 and IL-4) following lipopolysaccharide/interferon-γ stimulation. Consistently, TSG reversed the metabolic profiling of M1 macrophage toward the M2 status at intracellular energy levels. Surprisingly, the knockdown of an established metabolic enzyme pyruvate kinase M2 (PKM2) that is important for M1 switch in macrophages abolished the promotive effect of TSG on the M2 polarization. Further investigation revealed that TSG markedly downregulated the intracellular ratio of dimer/monomer to the tetramer of PKM2 without affecting its total protein expression, leading to a suppressed nuclear translocation of functioning PKM2 in macrophages for M1 differentiation. Taken together, we identified a novel mechanism for macrophage M2 polarization regulation by a small-molecule chemical that controls the quality (conformation) rather than the quantity (expression) of an intracellular M1-promoting metabolic enzyme, which offers a better understanding of the mechanisms of macrophage plasticity and has serious implication in translational strategies for the treatment of macrophage-mediated neurological diseases with natural bioactive products.

Most patients are at advanced stages when they are diagnosed with hepatocellular carcinoma, leading to poor prognosis and a low 5-year survival rate. Serological markers, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and liver biopsy are the common clinical diagnostic techniques for liver cancer. Effective interventions in the early stage will be beneficial to improve the prognosis of liver cancer patients and reduce the global burden. Therefore, it is urgent to develop new diagnostic methods to improve the diagnosis and management of liver cancer. Nanotechnology has become a new frontier subject in medical detection along with the application of nanomaterials in the manufacture of drug carriers, diagnostic tools, and therapeutic devices. Many studies have shown that nanoparticles (NPs) can be applied to the clinical diagnosis of liver cancer in combination with existing technologies, providing a new method for the early diagnosis of liver cancer. In this review, we elaborate on the theoretical basis and characteristics of NPs in the diagnosis of liver cancer, and the research progress and prospects of NPs in the diagnosis of liver cancer are summarized.

During the digital age of healthcare, it is crucial to utilize medical data scattered across different healthcare institutions to improve diagnostic precision and customize treatment strategies. A common solution to achieve this is establishing an authorization service that facilitates secure sharing of medical data and promotes interoperability among various healthcare institutions. However, there is a risk of a single point of failure because the majority of authorization systems in use rely on a central trusted service. This paper proposes DAMFSD, a decentralized authorization model with flexible and secure permissions delegation for medical data sharing. Specifically, patients can transfer their permissions to reliable institutions or individuals for flexible management and delegation while they retain control and monitor their permissions. We use cryptographic techniques for secure and fine-grained delegation and smart contracts to enable decentralized and flexible delegation. Finally, we performed a security analysis to demonstrate DAMFSD’s feasibility and conducted a performance evaluation on the permissioned blockchain to show its applicability.

In the U.S. alone, medication non-adherence is estimated to cause 1 in 10 hospitalizations, approximately 125,000 deaths annually, and cost the U.S. healthcare system just under $300 billion each year. Patients in medically underserved areas (MUAs) are particularly vulnerable to all forms of non-adherence and downstream morbidity and mortality; however, the extent to which primary medication non-adherence (i.e., prescription abandonment) affects the underserved is still largely unknown.

It has become an inevitable trend of human development to seek resources from the deep underground. However, rock encountered in deep underground engineering is usually in an anisotropic stress state (σ1>σ>σ3) due to the influences of geological structures and engineering disturbances. It is therefore essential to study the mechanical, seepage, and dynamic disaster behaviors of deep rock under true triaxial stress to ensure the safe operation of deep rock engineering and the efficient exploitation of deep resources. In recent years, experimental techniques and research on true triaxial rock mechanics have achieved fruitful results that have promoted the rapid development of deep rock mechanics; thus, it is necessary to systematically review and summarize these developments. This work first introduced several typical true triaxial testing apparatus and then reviewed the corresponding research progress on rock deformation, strength, failure mode, brittleness, and energy as well as the 3D volumetric fracturing (dynamic disaster) properties of deep rocks under true triaxial stress. Then, several commonly used true triaxial rock strength criteria and their applicability, the permeability characteristics and mathematical models of deep reservoir rocks, and the disaster-causing processes and mechanisms of disturbed volumetric fracturing (rockburst, compound dynamic disasters) in deep rock engineering were described. This work may provide an essential reference for addressing the true triaxial rock mechanics issues involved in deep rock engineering, especially regarding the stability of surrounding rock at depth, disaster prevention and control, and oil and gas exploitation.

Data regarding the association of the waist-to-height ratio (WHtR) with hypertension (HTN) are conflicting. Moreover, little information is available on the association between WHtR and HTN subtypes. Therefore, we aimed to investigate the associations between WHtR and the prevalence of HTN and its subtypes in a Chinese population. In the cross-sectional analysis, 13,947 adults from the China Hypertension Survey study were analysed. We examined the relationship between WHtR and the prevalence of HTN and its subtypes (isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systodiastolic hypertension (SDH)) using multivariate logistic regression analysis. A generalized additive model (GAM) and smooth curve fitting (penalized spline method) were also used. Overall, the mean WHtR was 0.50. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for HTN, ISH, IDH and SDH for each standard deviation (SD) increase in WHtR were 1.53 (1.45−1.61), 1.36 (1.28−1.44), 1.41 (1.20−1.65) and 1.47 (1.36−1.59), respectively. The fully adjusted smooth curve fitting revealed a linear association between WHtR and HTN, ISH, IDH, and SDH. Moreover, the positive associations between WHtR and HTN and its subtypes were more strong among younger adults (<60 compared with ≥60 years, Pvalues for interaction <0.001). These findings suggested that WHtR was positively associated with HTN and its subtypes, especially among younger adults (<60 years) in southern China.

The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls; the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.

ABSTRACTAging has become an irreversible trend in the world, the health problems caused by aging cannot be ignored. The physiological functions of human body begin to decline with aging, the decline of gastrointestinal function caused by aging is an important problem that needs to be resolved. In this work, we evaluated the anti-aging effect of uridine in the senescent gastric epithelial cell model, and found that the aging level of gastric epithelial cell was significantly down-regulated by uridine treatment, uridine could obviously down-regulate the ratio of the SA-β-gal-positive senescent cells. Furthermore, aging-related marker molecules (such as p16 and p21) were also significantly down-regulated under uridine treatment. Additionally, the levels of inflammation and oxidative stress were also significantly reduced by uridine treatment. Next, our further studies the effect of aging on FGF activity on gastric epithelial cell, and found that FGF/FGFR-mediated signaling pathways were significantly down-regulated. However, uridine treatment can not only alleviate the senescence of gastric epithelial cell, but also can partially restore the sensitivity of FGF signaling. Taken together, the current work indicates that uridine shows a good anti-aging effect, which lays a solid foundation for the related research in this filed.

ABSTRACTWe prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n= 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n= 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P= 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P= 0.01) and lower for adaptive (74.07% vs. 92.31% P= 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant’s development in gross motor (OR 6.49, 95% CI 1.37–30.20, P= 0.02) and adaptive (OR 0.18, 95% CI 0.05–0.71, P= 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation.Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.

Schizophrenia is a complex and highly heterogeneous mental illness with a prodromal period called clinical high risk (CHR) for psychosis before onset. Metabolomics is greatly promising in analyzing the pathology of complex diseases and exploring diagnostic biomarkers. Therefore, we conducted salivary metabolomics analysis in 83 first-episode schizophrenia (FES) patients, 42 CHR individuals, and 78 healthy controls with ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The mass spectrometry raw data have been deposited on the MetaboLights (ID: MTBLS3463). We found downregulated aromatic amino acid metabolism, disturbed glutamine and nucleotide metabolism, and upregulated tricarboxylic acid cycle in FES patients, which existed even in the CHR stage and became more intense with the onset of the schizophrenia. Moreover, differential metabolites can be considered as potential diagnostic biomarkers and indicate the severity of the different clinical stages of disease. Furthermore, three disordered pathways were closely related to peripheral indicators of inflammatory response, oxidative stress, blood–brain barrier damage, and salivary microbiota. These results indicate that the disorder of oral metabolism occurs earlier than the onset of schizophrenia and is concentrated and intensified with the onset of disease, which may originate from the dysbiotic salivary microbiota and cause the onset of schizophrenia through the peripheral inflammatory response and redox system, suggesting the importance of oral–brain connection in the pathogenesis of schizophrenia.

Separate-layer fracturing technology is one of the key stimulation technologies in the multi-layer reservoirs However, multiple fractures cannot evenly propagate due to the strong heterogeneity of the layers. In this paper, a three-dimensional model considering heterogeneity and fluid partitioning is developed to simulate the competitive propagation of multiple fractures in heterogeneous layered formation. The fracture pressure, fracture morphology, fluid volume and fracture length were systematically analyzed under different heterogeneous physical parameters. The following conclusions were obtained: (1) Formations with high rock strength, low permeability or high horizontal minimum principal stress will increase the fracture pressure and reduce the fluid volume within the fracture and fracture length. (2) Hydraulic fractures are easy to propagate into the interlayers if the pay zones have high rock strength and low permeability. (3) In heterogeneous layered formations, hydraulic fractures are more likely to gain competitive advantage in the high Young’s modulus and high permeability formations, while have the disadvantage in the high rock strength and high minimum principal stress formations. Poisson’s ratio has a little effect on the fracture propagation. This paper provides some helpful design guidance for the separate-layer fracturing in the heterogeneous layered formation.

Data on the association between homocysteine (Hcy) and the risk of chronic kidney disease (CKD) in patients with H-type hypertension were limited. This study aimed to examine the relation of Hcy with the prevalence of CKD and estimated glomerular filtration rate (eGFR) among Chinese adults with H-type hypertension.

AimsWe have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes.MethodsA total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively.ResultsPatients in both groups (ten in JP and 12 in JA) did not differ in local recurrence (p ≥ 0.999) and occurrence of metastases (p ≥ 0.999). Overall survival was similar in both groups (p = 0.858). Patients in the JP group had less range of motion (ROM) of the knee (p < 0.001) and lower MSTS scores (p = 0.010) compared with those of the JA group only at one year postoperatively. There was no difference between groups either at three years for ROM (p = 0.185) and MSTS score (p = 0.678) or at five years for ROM (p = 0.687) and MSTS score (p = 0.536), postoperatively. Patients in the JA group tended to have more complications (p = 0.074). Survival of primary reconstruction in the JP group was better than that of the JA group (p = 0.030).ConclusionCryoablation-aided joint-sparing surgery offers native joint preservation with comparable functional recovery and more durable reconstruction without jeopardizing oncological outcomes compared with conventional limb salvage surgery.Cite this article: Bone Joint J2021;103-B(8):1421–1427.

A stable catalyst, Pt/carbon nanotube (CNT) coated with N-doped carbon (Pt/CNT@CN), was designed to reduce selenite (Se(IV)) in water to elemental selenium by liquid-phase catalytic hydrogenation. Commercial Pt/C, pristine Pt/CNT, and carbon-coated Pt/CNT (Pt/CNT@C) were used for benchmarking. The Pt particles in Pt/CNT@CN were completely embedded beneath the coatings to minimize leaching and were not easily accessible to Se(IV). However, Schottky–Mott-type metal–carbon junctions that activate H2were formed on the coated catalyst, facilitating effective reduction of Se(IV). The initial activity of Pt/CNT@CN (900.5 mg L–1gcat–1h–1) was two times higher than that of commercial Pt/C (448.6 mg L–1gcat–1h–1). The commercial Pt/C and uncoated Pt/CNT lost their initial activities during reuse and were almost inactive after 10 cycles due to significant Pt leaching (>90%) during the reaction and acid-washing regeneration processes. Pt/CNT@CN maintained 33% of the initial activity after the first cycle and stabilized over the following 9 cycles due to effective protection of Pt particles by carbon coatings. After 10 cycles, the activity of Pt/CNT@CN was over 20 times higher than that of Pt/C and uncoated Pt/CNT. Overall, catalytic hydrogenation using carbon-coated-supported Pt catalysts is an effective and promising approach to remove Se(IV) in water.

As in other vertebrates, fish reproduction is tightly controlled by gonadotropin signaling. One of the most perplexing aspects of gonadotropin action on germ cell biology is the restricted expression of gonadotropin receptors in somatic cells of the gonads. Therefore, the identification of factors conveying the action of gonadotropins on germ cells is particularly important for understanding the mechanism of reproduction. Insulin-like growth factors (Igfs) are recognized as key factors in regulating reproduction by triggering a series of physiological processes in vertebrates. Recently, a novel member of Igfs called Igf3 has been identified in teleost. Different from the conventional Igf1 and Igf2 that are ubiquitously expressed in a majority of tissues, Igf3 is solely or highly expressed in the fish gonads. The role of Igf3 in mediating the action of gonadotropin through Igf type 1 receptor on several aspects of oogenesis and spermatogenesis have been demonstrated in several fish species. In this review, we will summarize existing data on Igf3. This new information obtained from Igf3 provides insight into elucidating the molecular mechanism of fish reproduction, and also highlights the importance of Igf system in mediating the action of gonadotropin signaling on animal reproduction.

The characteristics of fracture networks are of great significance for unconventional geo-energy exploitation such as shale oil, shale gas and geo-thermal extraction. Natural fractures and induced fractures after reservoir stimulation control the mechanical properties and fluid flow of the reservoirs. The quantitative characterization and reconstruction of rough fractures are essential for studying the fluid flow and mechanical properties of the reservoirs with complicated fracture networks. Based on vector statistics, a vector statistical method (VSM) for quantitative characterization of rough fractures is proposed and tested using 10 standard joint profiles. Furthermore, the growth vector counting method (counting method) and growth vector probability method (probability method) for single rough fractures in two-dimensional (2D) and three-dimensional (3D) models are proposed. Afterward, a morphology comparison and quantitative evaluation of single rough fractures before and after reconstruction are conducted. When the counting and probability methods are used to reconstruct single rough fractures, the difference in the tortuosity and fractal dimensions of the original and reconstructed fractures are less than 5% and 2.5%, respectively. It implies the counting and probability methods proposed herein can reconstruct rough fractures with approximate statistical characteristics and quantitative characterization parameters. Subsequently, the counting and probability methods for single rough fractures are further developed for 2D and 3D modeling of conventional and rough discrete fracture networks. The results indicate that the growth vector counting and probability methods proposed in this study have significant potential for rough discrete fracture network modeling. In addition, the merits and limitations of the proposed algorithms in modeling discrete fracture network models are discussed.

This article concentrates on ground vision guided autonomous landing of a fixed-wing Unmanned Aerial Vehicle (UAV) within Global Navigation Satellite System (GNSS) denied environments. Cascaded deep learning models are developed and employed into image detection and its accuracy promoting for UAV autolanding, respectively. Firstly, we design a target bounding box detection network BboxLocate-Net to extract its image coordinate of the flying object. Secondly, the detected coordinate is fused into spatial localization with an extended Kalman filter estimator. Thirdly, a point regression network PointRefine-Net is developed for promoting detection accuracy once the flying vehicle’s motion continuity is checked unacceptable. The proposed approach definitely accomplishes the closed-loop mutual inspection of spatial positioning and image detection, and automatically improves the inaccurate coordinates within a certain range. Experimental results demonstrate and verify that our method outperforms the previous works in terms of accuracy, robustness and real-time criterions. Specifically, the newly developed BboxLocate-Net attaches over 500 fps, almost five times the published state-of-the-art in this field, with comparable localization accuracy.

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription-PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3' untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

Background:As the last health care provider encountered before an opioid is dispensed, pharmacists have a vital role in reducing unnecessary opioid exposure while facilitating access to non-opioid alternatives. Objective:To characterize pharmacist perceptions in providing interventions for patients with an opioid prescription for acute pain. Methods:This cross-sectional survey was administered over 3 months to pharmacy preceptors affiliated with the University of Tennessee Health Science Center College of Pharmacy. The electronic survey utilized 7 demographical and baseline questions, 1 open-ended question, and 5 Likert-type scales to assess the following domains: responsibility in making decisions, willingness to provide information, comfort in speaking to patients, willingness to use a standing order, and importance of following up with patients. Results:Of the 380 participants invited to participate, 126 responded to at least one question and 90 completed all survey questions. Most participants were PharmD graduates practicing in hospital and community settings. Participants felt that opioids are frequently overprescribed and pharmacist interventions are often necessary. Most participants reported that pharmacists and physicians share similar responsibilities in making opioid-related decisions. Participants were willing to provide information about opioid alternatives but were only somewhat comfortable speaking to patients. Responses to the open-ended question revealed the following themes: Significance of educating the patient; Importance of alternatives to opioid medications; Impacts of pharmacist interventions; and Need for enhanced collaboration with physicians. Conclusions:Pharmacists face complex issues with limited clinical guidance when providing opioid-related interventions. Future research is needed to develop evidence-based clinical support tools and collaborative practice models.

In this work, we report a successful extension of the family of light-emitting colloidal carbon nanostructures to a number of different shapes and morphologies, namely, carbon nanorolls (CNRs) and carbon nanobelts (CNBs). Near infrared (NIR)-emissive CNRs were synthesized viaa solvothermal fusion of carbon dots (CDs) triggered by a dehydration process of their surface functional groups. They appear in a form of short cylinders, with diameters ranging from 20 to 40 nm and cylinder lengths ranging from 7 to 20 nm. In ethanol solution, CNRs have a maximum absorption peak at 665 nm and a NIR emission band extending from 650 to 800 nm, with a photoluminescence quantum yield of 9.2%. Intriguingly, the rolled structure of CNRs can be uncoiled under 655 nm laser irradiation (power density 1 W·cm–2) of their solution in ethanol, forming CNBs with a width of 7–20 nm and lengths reaching several hundreds of nanometers, which is accompanied by a considerably decreased absorption band at 665 nm and a decreased NIR emission. This unfolding is ascribed to the decrease of the strength of interlayer hydrogen bonding, owing to the photothermally induced dehydration and further carbonization of the CNRs. Alongside the decreased NIR emission, CNBs exhibit enhanced green and red emissions under UV and green light excitation, respectively, which allows us to demonstrate multiple-level luminescence encryptions on a paper stamped with CNR- and CNB-inks.

Schizophrenia is a severe neuropsychiatric disorder with core features including hallucinations, delusions, and cognition deficits. Accumulating evidence has implicated abnormal DNA methylation in the development of schizophrenia. However, the mechanisms by which DNA methylation changes alter the risk for schizophrenia remain largely unknown. We recently carried out a DNA methylome study of peripheral blood samples from 469 first-episode patients with schizophrenia and 476 age- and gender-matched healthy controls of Han Chinese origin. Genomic DNA methylation patterns were quantified using an Illumina Infinium Human MethylationEPIC BeadChip. We identified multiple differentially methylated positions (DMPs) and regions between patients and controls. The most significant DMPs were annotated to genes C17orf53, THAP1 and KCNQ4 (KV7.4), with Bonferroni-adjusted Pvalues of 1.34×10-12, 1.15×10-11, and 3.11×10-11, respectively. In particular, KCNQ4 encodes a voltage-gated potassium channel of the KV7 family, which is linked to neuronal excitability. The genes associated with top-ranked DMPs also included many genes involved in nervous system development, such as LIMK2 and TMOD2. Gene ontology analysis of the differentially methylated genes further identified strong enrichment of neuronal networks, including neuron projection extension, axonogenesis and neuron apoptotic process. Finally, we provided evidence that schizophrenia-associated epigenetic alterations co-localize with genetic susceptibility loci. By focusing on first-episode schizophrenia patients, our investigation lends particularly strong support for an important role of DNA methylation in schizophrenia pathogenesis unconfounded by the effects of long-term antipsychotic medication or disease progression. The observed DNA methylation aberrations in schizophrenia patients could potentially provide a valuable resource for identifying diagnostic biomarkers and developing novel therapeutic targets to benefit schizophrenia patients.

Currently, the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention. Still, the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination. In this study, we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens. Briefly, endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered, both as delivery vehicles and adjuvants. Then, these nanocarriers are coated with lipids and B16-OVA tumor cell membranes, so the biomembrane proteins can serve as tumor-specific antigens. It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect, while membrane proteins including tumor associated antigen were transferred onto the nanocarriers. It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells, promote their maturation and antigen-presentation, facilitate lymph retention, and trigger obvious immune response. It was confirmed that the biomimetic vaccine could induce strong T-cell response, exhibit excellent tumor therapy and prophylactic effects, and simultaneously possess nice biocompatibility. In general, the present investigation might provide insights for the further design and application of antitumor vaccines.

Intercropping, which gains productivity and ecological benefits through plant facilitative interactions, is a practice often associated with sustainable agriculture. In such systems, arbuscular mycorrhizal (AM) fungi and the hyphal networks play key roles in plant facilitation by promoting connectivity, mediating interplant transfer of metabolic resources, and managing weeds, pathogens, and contaminants. This review states that the symmetrically or unsymmetrically delivered resources via AM fungi are imperative to maintain facilitative interactions between intercrops. In addition, the responses of AM fungi to intercropping are also discussed, including changes in abundance, diversity, community composition and colonization level. Although general proliferations in AM fungi via intercropping have been shown, the plant hosts and neighbors may exert different influences on AM fungi. Therefore, further research is needed in quantifying the mediating role of AM fungi on outputs of intercropping systems, clarifying the driving forces, and exploring the causation between these processes and the changes in AM fungi themselves. To conclude, the integration with AM fungi extends the understanding of key soil biological processes driving plant facilitation and will guide efforts to optimizing intercropping systems.

To achieve high-temperature-sensing sensitivity, a new strategy of optical thermometry is designed based on the synergetic luminescence of the radiative emission of lanthanide (Ln) ions and defect-related luminescence in ZrO2:Gd3+nanoparticles. By X-ray diffraction, Raman spectroscopy, electron paramagnetic resonance spectroscopy, X-ray photoelectron spectroscopy, diffuse reflectance spectroscopy, temperature-dependent photoluminescence (PL) spectroscopy, decay time measurements, and thermoluminescence study, we investigate the defect nature, the relationship between Gd3+ions and defect centers, the PL property, and the thermometric performance. Under UV excitation, the broad emission band (λmax= 400 nm) observed is ascribed to the carbon impurities and oxygen vacancies, while the sharp emission peak (λmax= 315 nm) is from Gd3+ions. Originating from their diverse thermal responses, the fluorescence intensity ratio of defect-related luminescence to Gd3+emission displays excellent absolute sensitivity (Sa-max= 6.408 K–1), relative sensitivity (Sr-max= 3.452% K–1), and good signal discrimination (Δλmax= 85 nm), which are much higher than those reported previously for ratiometric thermal-sensing materials. This work may not only pave a way for boosting the sensing sensitivity of optical thermometers but also provide inspiration for extending the application of defect-related luminescent materials in thermal detection.

Mullite castables are widely used in the hot metal pretreatment processing equipment. In this work, the effects of modification of alumina bubbles with silica sol on the properties of mullite castables were studied. After the alumina bubbles were modified by silica sol, the bulk density of the samples was slightly increased, and the apparent porosity was decreased. The cold modulus of rupture values of experimental castables increased remarkably after drying at 110 °C and heating at 1400 °C for 3 h. The thermal expansion of the samples was obviously increased, while the thermal conductivity of the samples was decreased significantly. More columnar mullite crystals were formed at the alumina bubble/matrix interface after the alumina bubble modification and form a continuous inter-locking network structure, which was helpful to improve castables’ thermal shock resistance.

Cyclic nucleotide–gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ligand activation are largely undefined. We report both closed- and open-state atomic cryo-EM structures of a full-length Caenorhabditis eleganscyclic GMP−activated channel TAX-4, reconstituted in lipid nanodiscs. These structures, together with computational and functional analyses and a mutant channel structure, reveal a double-barrier hydrophobic gate formed by two S6 amino acids in the central cavity. cGMP binding produces global conformational changes that open the cavity gate located ~52 Å away but do not alter the structure of the selectivity filter—the commonly presumed activation gate. Our work provides mechanistic insights into the allosteric gating and regulation of CN-gated and nucleotide-modulated channels and CNG channel−related channelopathies.

Blue-violet light can not only enhance the total content of biomass and glucoside but also enrich the taste of the fruit. Thus, it is meaningful to study the blue-violet luminescent materials for plant cultivation. In this study, titanium (IV) -activated CaYAlO4(CYAO) phosphors were synthesized by conventional high-temperature solid–state reaction. X-ray powder diffraction was employed to analyze the crystal-structure of CYAO. It is found that the doped Ti4+ions do not change obviously the crystal structure of phosphors. Upon 246 nm excitation, CaYAl1-xO4:xTi4+phosphors exhibit broad blue-violet emission band peaking at 395 nm, which can be attributed to the charge transfer of Ti4+–O2–. Moreover, this phosphor exhibits strong thermal stability. The luminescence emission intensity at 150 °C maintained about 91 mol% of its initial value at room temperature. Additionally, the electron transition process and concentration quenching mechanism of CaYAl1–xO4:xTi4+are discussed in detail. The excellent luminescent properties indicate that CaYAl1-xO4:xTi4+phosphor may have promising application in indoor plant cultivation.

Highly efficient organic light-emitting diodes (OLEDs) employing metal-free thermally activated delayed fluorescence (TADF) emitters have attracted much attention in recent years. Efficient TADF mainly occurs in charge-transfer (CT) molecules. Here, we demonstrate that a small dipole moment for TADF emitters in the S1state is key for device stability by comparing two green TADF emitters with the same moieties but different types of linker. The compound 1AC-TRZ with a 9,9-dimethyl-9,10-dihydroacridine donor and a triphenyltriazine acceptor attached at the 1- and N-positions of carbazole has a smaller excited-state dipole moment (11 D) than the 3- and N-substituted analog 3AC-TRZ (30 D). Although the emission spectra and efficiencies of their devices are similar, the operational lifetime of the 1AC-TRZ-based device is much longer than that of the 3AC-TRZ-based device. Time-resolved emission spectra indicate that the S1energy of 3AC-TRZ in doped films is higher than that of 1AC-TRZ at the start of nanosecond solvation relaxation. A photodegradation experiment suggests that the short-term existence (<1 ns) of high energy (>2.9 eV) excitons can hasten the upconversion-induced degradation in films. Our study reveals a relationship between solid-state solvation and OLED stability and provides a new guideline for designing stable green and blue TADF emitters.

The expression and function of long noncoding RNAs (lncRNAs) in the development of hypoxic pulmonary hypertension (HPH), especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs), are largely unknown. Herein, we examined the expression and role of lncRNA-maternally expressed gene 3 (lncRNA-MEG3) in HPH. lncRNA-MEG3 was significantly increased and primarily localized in the cytoplasm of hypoxic PASMCs. lncRNA-MEG3 knockdown by lung-specific delivery of small interfering RNAs (siRNAs) significantly inhibited the development of HPH in vivo. Silencing of lncRNA-MEG3 by siRNAs and gapmers attenuated proliferation and cell-cycle progression in both PASMCs from idiopathic pulmonary arterial hypertension (iPAH) patients (iPAH-PASMCs) and hypoxia-exposed PASMCs in vitro. Mechanistically, we found that lncRNA-MEG3 interacts with and leads to the degradation of microRNA-328-3p (miR-328-3p), leading to upregulation of insulin-like growth factor 1 receptor (IGF1R). Additionally, higher expression of lncRNA-MEG3 and IGF1R and lower expression of miR-328-3p were observed in iPAH-PASMCs and relevant HPH models. These data provide insights into the contribution of lncRNA-MEG3 to HPH. Upregulation of lncRNA-MEG3 sequesters cytoplasmic miR-328-3p, eventually leading to expression of IGF1R, revealing a regulatory mechanism by lncRNAs in hypoxia-induced PASMC proliferation.

Norfloxacin, a quinolone antibiotic pollutant, posed a significant threat to environment and human being health. In this study, hydrotalcite-based g-C3N4composites were produced using electrostatic self-assembly and the structural memory effect of hydrotalcite to optimize their adsorption-degradation of norfloxacin under visible-light illumination. Optimized hydrotalcite and g-C3N4composite (750°C, 40wt% of g-C3N4) exhibited a highest photo-degradation rate constant of 1.8×10-2min-1with 83.98% norfloxacin degradation achieved within 1.5h under visible-light, surpassing that of bare g-C3N4and hydrotalcite photocatalysts. The synergistic effects of the composite, such as uniform flower-like micro-morphology and rich mesoporous structure, resulted in a large specific surface area (58.67 m2/g), abundant active sites, and good photo-generated charge separation efficiency. All these facilitated both sorption (7.95mg/g) and subsequent visible-light degradation of norfloxacin. Furthermore, the superior photocatalytic performance observed in the degradation of norfloxacin under visible-light illumination was assigned to the effective transport of photogenerated electrons and holes between hydrotalcite and g-C3N4components. The work highlights the potentials of hydrotalcite and g-C3N4composites as an excellent photocatalyst for environment remediation and water treatment.

In recent years, carbon monoxide (CO) has garnered increased attention as a novel green therapy for hepatocellular carcinoma (HCC) treatment. However, the CO donor is still limited in clinical application due to its lack of targeted ability and unstable release rate. Here, self-assembled amphiphilic nanomicelles glucose-polyethylene glycol (PEG)–lipoic acid (LA)–Fe2(CO)6(Glu-Fe2(CO)6) are first designed as a CO donor and synthesized via a chemical method, combining glucose with Fe2(CO)6through PEG–LA. Some advantages of this tumor-targeted Glu-Fe2(CO)6delivery system include (I) good water-solubility, (II) the glutathione responsive CO slow release, (III) the active tumor-targeted ability of glucose as targeted ligands, and (IV) outstanding efficacy of antitumor and safety of CO therapy of HCC both in vitro and in vivo. These findings suggest that Glu-Fe2(CO)6nanomicelles hold promise for enhancing antitumor therapeutic capabilities, presenting a novel tumor-targeted delivery strategy in gas therapy for HCC treatment.