A correlated ferromagnetic polar metal by design.

Polar metals have recently garnered increasing interest because of their promising functionalities. Here we report the experimental realization of an intrinsic coexisting ferromagnetism, polar distortion and metallicity in quasi-two-dimensional Ca3Co3O8. This material crystallizes with alternating stacking of oxygen tetrahedral CoO4 monolayers and octahedral CoO6 bilayers. The ferromagnetic metallic state is confined within the quasi-two-dimensional CoO6 layers, and the broken inversion symmetry arises simultaneously from the Co displacements. The breaking of both spatial-inversion and time-reversal symmetries, along with their strong coupling, gives rise to an intrinsic magnetochiral anisotropy with exotic magnetic field-free non-reciprocal electrical resistivity. An extraordinarily robust topological Hall effect persists over a broad temperature-magnetic field phase space, arising from dipole-induced Rashba spin-orbit coupling. Our work not only provides a rich platform to explore the coupling between polarity and magnetism in a metallic system, with extensive potential applications, but also defines a novel design strategy to access exotic correlated electronic states.

Artificial Domain Patterning in Ultrathin Ferroelectric Films via Modifying the Surface Electrostatic Boundary Conditions.

Nanoscale spatially controlled modulation of the properties of ferroelectrics via artificial domain pattering is crucial to their emerging optoelectronics applications. New patterning strategies to achieve high precision and efficiency and to link the resultant domain structures with device functionalities are being sought. Here, we present an epitaxial heterostructure of SrRuO3/PbTiO3/SrRuO3, wherein the domain configuration is delicately determined by the charge screening conditions in the SrRuO3 layer and the substrate strains. Chemical etching of the top SrRuO3 layer leads to a transition from in-plane a domains to out-of-plane c domains, accompanied by a giant (>105) modification in the second harmonic generation response. The modulation effect, coupled with the plasmonic resonance effect from SrRuO3, enables a highly flexible design of nonlinear optical devices, as demonstrated by a simulated split-ring resonator metasurface. This domain patterning strategy may be extended to more thin-film ferroelectric systems with domain stabilities amenable to electrostatic boundary conditions.

Electric-Field Control of Perpendicularly Magnetized Ferrimagnetic Order and Giant Magnetoresistance in Multiferroic Heterostructures.

Electrical control of magnetism is highly desirable for energy-efficient spintronic applications. Realizing electric-field-driven perpendicular magnetization switching has been a long-standing goal, which, however, remains a major challenge. Here, electric-field control of perpendicularly magnetized ferrimagnetic order via strain-mediated magnetoelectric coupling is reported. We show that the gate voltages isothermally toggle the dominant magnetic sublattice of the compensated ferrimagnet FeTb at room temperature, showing high reversibility and good endurance under ambient conditions. By implementing this strategy in FeTb/Pt/Co spin valves with giant magnetoresistance (GMR), we demonstrate that the distinct high and low resistance states can be selectively controlled by the gate voltages with assisting magnetic fields. Our results provide a promising route to use ferrimagnets for developing electric-field-controlled, low-power memory and logic devices.

A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Clinical study of Microendoscopic Discectomy + Fibrous Ring Suture Versus Microendoscopic Discectomy alone in the treatment of lumbar disc herniation in young and middle-aged patients.

Objective: To compare the clinical efficacy of microendoscopic discectomy + fibrous ring suture versus microendoscopic discectomy alone in the treatment of lumbar disc herniation (LDH) in young and middle-aged patients. Methods: A retrospective analysis was performed on the clinical data of 66 young and middle-aged patients with single-segment LDH diagnosed in Orthopedic Hospital of Henan Province from October 2019 to October 2022. All patients were divided into two groups: the microendoscopic discectomy + fibrous ring suture group and the microendoscopic discectomy alone group, with 33 cases in each group. The Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) scores of the two groups were recorded before surgery and six and twelve months after surgery. Results: Both groups completed the surgery and postoperative follow-up successfully and showed no statistically significant differences in terms of incision length, duration of surgery, intraoperative blood loss and length of hospital stay (all P>0.05). VAS, ODI and JOA scores were significantly improved in both groups at 6 and 12 months after surgery compared with those before surgery (all P<0.05). The two groups were similar in terms of excellent and good rates of postoperative modified MacNab Evaluation Criteria, with no statistically significant differences. No serious complications were observed in the two groups during and after surgery. Conclusion: Both of the two surgical methods are effective in the treatment of LDH in young and middle-aged patients, and microendoscopic discectomy + fibrous ring suture in particular may be preferred because it results in significant improvement in patients' VAS and ODI scores.

Intercrystalline Channels at Subnanometer Scale for Precise Molecular Nanofiltration.

Membrane-based technologies can provide cost-effective and energy-efficient methods for various separation processes. The key goal is to develop materials with uniform, tunable, and well-defined subnanometer-scale channels. Suitable membrane materials should have high selectivity and permeance and can be manufactured in a robust and scalable fashion. Here, we report the construction of sub-1 nm intercrystalline channels with such characteristics and elucidate their transport properties. These channels are formed by assembling 3D aluminum formate crystals during the amorphous-to-crystalline transformation process. By controlling the transformation time, the channel size can be tuned from the macroscopic scale to nanometer scale. The resulting membranes exhibit tailored selectivity and permeance, with molecular weight cutoffs ranging from around 300 Da to approximately 650 Da, and ethanol permeance ranging from 0.8 to 22.0 L m-2 h-1 bar-1. We further show that liquid flow through these channels changes from viscosity-dominated continuum flow to subcontinuum flow, which can be described by a modified Hagen-Poiseuille model. Our strategy provides a new scalable platform for applications that commonly exploit nanoscale mass transport.

Zirconium Metal-Organic Cages: Synthesis and Applications.

ConspectusFor the last two decades, materials scientists have contributed to a growing library of porous crystalline materials. These synthetic materials are typically extended networks, including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), or discrete materials like metal-organic cages (MOCs) and porous organic cages (POCs). Advanced porous materials have shown promise for various applications due to their modular nature and structural tunability. MOCs have recently garnered attention because of their molecularity that bestows them with many unique possibilities (e.g., solution-processability, structural diversity, and postsynthetic processability).MOCs are discrete molecular assemblies of organic ligands coordinated with either metal cations or metal oxide clusters of different nuclearities, resulting in architectures with inherent porosity. Notably, the molecular nature of MOCs endows them with easy solution-processability unattainable with traditional framework materials. To date, a number of stable MOCs have been reported, such as those based on Rh (Rh-O bond energy: 405 ± 42 kJ/mol), Fe (Fe-O bond energy: 407.0 ± 1.0 kJ/mol), Cr (Cr-O bond energy: 461 ± 8.7 kJ/mol), Ti (Ti-O bond energy: 666.5 ± 5.6 kJ/mol), and Zr (Zr-O bond energy: 766.1 ± 10.6 kJ/mol). Paddle-wheel MOCs have also shown great stability in aqueous environments due to their rigid backbones. The zirconium MOC (Zr-MOCs) family emerges as a class of very robust cages for which their high bond energy endows them with high hydrothermal stability.In 2013, we reported the first four zirconocene tetrahedrons assembled from trinuclear zirconium oxide clusters with ditopic or tritopic organic ligands. Since then, significant progress in the rational design of Zr-MOC has led to an assortment of structures dedicated to meaningful applications.In this Account, we highlight the recent progress in synthesizing Zr-MOCs and Zr-MOC-based higher dimensional frameworks and their applications dedicated in our laboratories and beyond. The general Zr-MOC synthetic strategy involves assembling Zr trinuclear clusters with organic ligands (rigid or flexible) containing various functional groups. This chemistry has afforded cages with structural versatility and active sites, e.g., amino groups, for postsynthetic modifications (PSMs). Since the extrinsic porosity of cage-based frameworks is relatively weak, the resulting frameworks are susceptible to structural rearrangement after solvent removal. To circumvent this limitation, increasing the hydrogen bond ratio and strength between interlinked cages and conducting in situ catalytic polymerizations have been reported to afford permanently porous structures amenable to host-guest reactions.To expand their potential applications, multifunctional Zr-MOCs are highly desired. Such multivariate MOCs can be attained by either employing the isoreticular expansion strategy to create MOCs with high surface areas or using mixed-ligand approaches to afford heterogeneous MOCs. In addition, amorphous MOCs, flexible organic ligands, new functionalities, and MOC-based extended networks are exciting new approaches to developing materials with structural versatility and enhanced characteristics. Thereby, we believe the stability and versatility of the Zr-MOC family hold great potential in expanding and addressing challenging applications.

Charge equilibration model with shielded long-range Coulomb for reactive molecular dynamics simulations.

Atomic description of electrochemical systems requires reactive interaction potential to explicitly describe the chemistry between atoms and molecules and the evolving charge distribution and polarization effects. Calculating Coulomb electrostatic interactions and polarization effects requires a better estimate of the partial charge distribution in molecular systems. However, models such as reactive force fields and charge equilibration (QEq) include Coulomb interactions up to a short-distance cutoff for better computational speeds. Ignoring long-distance electrostatic interaction affects the ability to describe electrochemistry in large systems. We studied the long-range Coulomb effects among charged particles and extended the QEq method to include long-range effects. By this extension, we anticipate a proper account of Coulomb interactions in reactive molecular dynamics simulations. We validate the approach by computing charges on a series of metal-organic frameworks and some simple systems. Results are compared to regular QEq and quantum mechanics calculations. The study shows slightly overestimated charge values in the regular QEq approach. Moreover, our method was combined with Ewald summation to compute forces and evaluate the long-range effects of simple capacitor configurations. There were noticeable differences between the calculated charges with/without long-range Coulomb interactions. The difference, which may have originated from the long-range influence on the capacitor ions, makes the Ewald method a better descriptor of Coulomb electrostatics for charged electrodes. The approach explored in this study enabled the atomic description of electrochemical systems with realistic electrolyte thickness while accounting for the electrostatic effects of charged electrodes throughout the dielectric layer in devices like batteries and emerging solid-state memory.

Anisotropic Magnon Spin Transport in Ultrathin Spinel Ferrite Thin Films─Evidence for Anisotropy in Exchange Stiffness.

Magnon-mediated spin flow in magnetically ordered insulators enables long-distance spin-based information transport with low dissipation. In the materials studied to date, no anisotropy has been observed in the magnon propagation length as a function of propagation direction. Here, we report measurements of magnon spin transport in a spinel ferrite, magnesium aluminum ferrite MgAl0.5Fe1.5O4 (MAFO), which has a substantial in-plane 4-fold magnetic anisotropy. We observe spin diffusion lengths > 0.8 µm at room temperature in 6 nm films, with spin diffusion lengths 30% longer along the easy axes compared to the hard axes. The sign of this difference is opposite to the effects just of anisotropy in the magnetic energy for a uniform magnetic state. We suggest instead that accounting for anisotropy in exchange stiffness is necessary to explain these results. These findings provide an approach for controlling magnon transport via strain, which opens new opportunities for designing magnonic devices.

Optimisation of the Extraction Process of Naringin and Its Effect on Reducing Blood Lipid Levels In Vitro.

The naringin extraction process was optimised using response surface methodology (RSM). A central component design was adopted, which included four parameters: extraction temperature (X1), material-liquid ratio (X2), extraction time (X3), and ultrasonic frequency (X4) of 74.79 °C, 1.58 h, 1:56.51 g/mL, and 28.05 KHz, respectively. Based on these optimal extraction conditions, naringin was tested to verify the model's accuracy. Naringin yield was 36.2502 mg/g, which was equivalent to the predicted yield of 36.0124 mg/g. DM101 macroporous adsorption resin was used to purify naringin. The effects of loading concentration, loading flow rate, and sample pH on the adsorption rate of naringin and the effect of ethanol concentration on the desorption rate of naringin were investigated. The optimum conditions for naringin purification using macroporous resins were determined. The optimal loading concentration, sample solution pH, and loading flow rate were 0.075 mg/mL, 3.5, and 1.5 mL/min, respectively. Three parallel tests were conducted under these conditions, and the average naringin yield was 77.5643%. Naringin's structure was identified using infrared spectroscopy and nuclear magnetic resonance. In vitro determination of the lipid-lowering activity of naringin was also conducted. These results showed that naringin has potential applications as a functional food for lowering blood lipid levels.

CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study.

BACKGROUND: This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity. METHODS: This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres. RESULTS: This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03-2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways. CONCLUSIONS: The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.

FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication characterized by learning and memory deficits. In diabetic patients, hyperactivated hypothalamic-pituitary-adrenal (HPA) axis leads to abnormal increase of glucocorticoids (GCs), which causes the damage of hippocampal neurons and cognitive impairment. In this study we investigated the cognition-improving effects of a non-steroidal glucocorticoid receptor (GR) antagonist 5-chloro-N-[4-chloro-3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (FX5) in diabetic mice. Four weeks after T1DM or T2DM was induced, the mice were administered FX5 (20, 40 mg·kg-1·d-1, i.g.) for 8 weeks. Cognitive impairment was assessed in open field test, novel object recognition test, Y-maze test, and Morris water maze test. We showed that FX5 administration significantly ameliorated the cognitive impairments in both type 1 and 2 diabetic mice. Similar cognitive improvement was observed in diabetic mice following brain GR-specific knockdown by injecting AAV-si-GR. Moreover, AAV-si-GR injection occluded the cognition-improving effects of FX5, suggesting that FX5 functioning as a non-steroidal GR antagonist. In PA-treated primary neurons (as DCI model in vitro), we demonstrated that FX5 (2, 5, 10 µM) dose-dependently ameliorated synaptic impairment via upregulating GR/BDNF/TrkB/CREB pathway, protected against neuronal apoptosis through repressing GR/PI3K/AKT/GSK3ß-mediated tauopathy and subsequent endoplasmic reticulum stress. In LPS-treated primary microglia, FX5 dose-dependently inhibited inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway. These beneficial effects were also observed in the hippocampus of diabetic mice following FX5 administration. Collectively, we have elucidated the mechanisms underlying the beneficial effects of non-steroidal GR antagonist FX5 on DCI and highlighted the potential of FX5 in the treatment of the disease.

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study.

BACKGROUND: Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. METHODS: This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. RESULTS: At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. CONCLUSIONS: Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.

Intervention Effect of Taurine on LPS-Induced Intestinal Mechanical Barrier Injury in Piglets.

Taurine has the advantages of being safe, highly efficient, chemically stabile, and biologically active, together with having versatile functions. Presently, it is employed as a veterinary feed additive in animal research. The tight junctions that constitute the intestinal epithelial cells are the most critical structures for ensuring regular and uninterrupted digestion and absorption of food by the intestinal mucosa, while at the same time resisting invasions by toxins. The purpose of this study was to investigate the protective effect and mechanism of taurine action on intestinal mechanical barrier function of piglets that were infected with LPS. The results showed that 0.3% taurine inhibits LPS-driven increase in intestinal permeability and intestinal mucosal injury, the rise in the ratio of villus length to crypt depth within the duodenum, jejunum, and ileum, and the significant enhancement in the expression of tight junction protein-related genes. In summary, dietary taurine significantly reduces intestinal mucosal structural damage and intestinal mucosal permeability while increasing gene expression of tight junction proteins of the intestinal mucosa of piglets induced by LPS, thereby enhancing the effect of intestinal mucosal mechanical barriers.

Taurine Prevents LPS-Induced Liver Injury in Weaned Piglets.

This study employed taurine as a feed additive to explore the prophylactic effect of taurine on LPS-induced hepatic injury in piglets. The pathological shifts within hepatic tissue were observed by HE staining. Serum levels of ALT and AST together with SOD, CAT, GSH-PX activity, and MDA serum and liver levels were detected. TUNEL was used to detect apoptosis, while qPCR was employed to detect HO-1, Nrf-2, Bcl2, BAX, Caspase-3, and NF- κB p65 transcriptomic expression levels. TRL4, Caspase-3, Nrf-2, and NF- κB p-p65/NF- κB p65 were detected by Western blot. The results revealed that taurine reduces LPS-induced pathological damage of hepatic tissue and reduces the levels of ALT and AST in pig serum. The transcriptomic expression levels of HO-1 and Nrf-2 were upregulated, and proteomic expression of Nrf-2 was increased. SOD, CAT, and GSH-PX activity was elevated, while MDA content was reduced in serum and liver. The levels of mRNA of BAX and Caspase-3 were downregulated, but mRNA content of Bcl2 was increased, and the protein levels of TRL4, NF-κB p-p65/NF-κB p65, and Caspase-3 were diminished. Overall, the degree of hepatocyte apoptosis was also significantly reduced. In conclusion, taurine reduces LPS-induced injury of piglet liver, while reducing hepatocyte apoptotic levels. These data provide a scientific basis for the selection of animal feed additives and lay a foundation for the healthy and sustainable development of the porcine industry.

Multivariate Polycrystalline Metal-Organic Framework Membranes for CO2/CH4 Separation.

Membrane technology is attractive for natural gas separation (removing CO2, H2O, and hydrocarbons from CH4) because of membranes' low energy consumption and small environmental footprint. Compared to polymeric membranes, microporous inorganic membranes such as silicoaluminophosphate-34 (SAPO-34) membrane can retain their separation performance under conditions close to industrial requirements. However, moisture and hydrocarbons in natural gas can be strongly adsorbed in the pores of those membranes, thereby reducing the membrane separation performance. Herein, we report the fabrication of a polycrystalline MIL-160 membrane on an Al2O3 substrate by in situ hydrothermal synthesis. The MIL-160 membrane with a thickness of ca. 3 µm shows a remarkable molecular sieving effect in gas separation. Besides, the pore size and environment of the MIL-160 membrane can be precisely controlled using reticular chemistry by regulating the size and functionality of the ligand. Interestingly, the more polar fluorine-functionalized multivariate MIL-160/CAU-10-F membrane exhibits a 10.7% increase in selectivity for CO2/CH4 separation and a 31.2% increase in CO2 permeance compared to those of the MIL-160 membrane. In addition, hydrophobic MIL-160 membranes and MIL-160/CAU-10-F membranes are more resistant to water vapor and hydrocarbons than the hydrophilic SAPO-34 membranes.

Development of a risk-stratification scoring system for predicting lymphovascular invasion in breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer. METHODS: A total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29-86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors' institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system. RESULTS: Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872). CONCLUSION: This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.

Light source for comfortable lighting and trapping pests in tea gardens based on solar-like lighting.

A large amount of tea is produced every year. Tea is often harmed by pests during the cultivation process, causing great economic damage. In this paper, we simulated a kind of light source for comfortable lighting and trapping pests based on solar-like lighting. We investigated three combinations of white LEDs and monochromatic LEDs for solar-like trapping light. The optimal combination of white LEDs and monochromatic LEDs was determined by the production cost and the spectral phototaxis ratio. We used TracePro for the trapping light mixing design. The results show that the combination of the cold white LED and six kinds of monochromatic LEDs is the best for trapping pests. A light source for comfortable lighting and trapping pests based on solar-like lighting with the color temperature of 7285 k, color coordinates of (0.3052, 0.3031), and color rendering index of 70 is obtained. The trapping light can not only be used as functional lighting but can also be applied to reduce the use of pesticides and improve the quality of tea.

PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-κB signalling.

The upregulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) was reported to be involved in regulating the levels of inflammatory markers and apoptosis in macrophages. This study aims to investigate the function and regulation of PCSK9 in myocardial ischaemia. The results of our study showed dramatically increased expression of PCSK9 induced by hypoxia/reoxygenation (H/R) stress rather than by apoptosis in primary murine cardiomyocytes and HL-1 cells. Moreover, PCSK9 promoted H/R-induced pro-inflammatory cytokine release from macrophages, while silencing of PCSK9 inhibited the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß. Additionally, PCSK9 facilitated the release of pro-inflammatory cytokines from macrophages under H/R conditions, which decreased cardiomyocyte viability and promoted apoptosis of cardiomyocytes. For the underlying mechanisms, we identified PCSK9-induced NF-κB activation as being involved in the cardiomyocyte apoptosis, which was blocked by the NF-κB inhibitor BAY 11-7082. Collectively, this study provides new insights into the therapeutic possibility of regulating PCSK9 in cardiomyocytes for the treatment of ischaemic cardiomyopathy.

Self-Assembly of Highly Stable Zirconium(IV) Coordination Cages with Aggregation Induced Emission Molecular Rotors for Live-Cell Imaging.

The self-assembly of highly stable zirconium(IV)-based coordination cages with aggregation induced emission (AIE) molecular rotors for in vitro bio-imaging is reported. The two coordination cages, NUS-100 and NUS-101, are assembled from the highly stable trinuclear zirconium vertices and two flexible carboxyl-decorated tetraphenylethylene (TPE) spacers. Extensive experimental and theoretical results show that the emissive intensity of the coordination cages can be controlled by restricting the dynamics of AIE-active molecular rotors though multiple external stimuli. Because the two coordination cages have excellent chemical stability in aqueous solutions (pH stability: 2-10) and impressive AIE characteristics contributed by the molecular rotors, they can be employed as novel biological fluorescent probes for in vitro live-cell imaging.