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Keywords: enzymes; high-order structure; Lysosomal membrane permeabilization; peptides; Self-assembly EN enzymes high-order structure Lysosomal membrane permeabilization peptides Self-assembly 1 1 1 09/22/21 20210927 NES 210927 B Supramolekulare Chemie b Die strukturbasierte Programmierung supramolekularer Assemblierungen in lebenden Zellen zur selektiven Hemmung von Krebszellen wird von Huaimin Wang et al. im Forschungsartikel auf S. 21978 vorgestellt. Frontispiz: Structure-Based Programming of Supramolecular Assemblies in Living Cells for Selective Cancer Cell Inhibition Enzymes, high-order structure, Lysosomal membrane permeabilization, peptides, Self-assembly. [Extracted from the article]

These colloidal motors could autonomously move at a speed of ca. 35 body lengths per second in the presence of an acoustic field, and could also actively seek and be internalized by cancer cells, which could be marked in real time through the photoluminance effect. Keywords: Liquid metal; Nanomotor; Colloidal motor; Acoustic propulsion; Gallium EN Liquid metal Nanomotor Colloidal motor Acoustic propulsion Gallium 966 966 1 09/08/21 20210901 NES 210901 B Rodlike liquid metal gallium-based colloidal motors b with broad light absorbance and photoluminance were prepared by a simple sonication crushing method. Liquid metal, Nanomotor, Colloidal motor, Acoustic propulsion, Gallium. [Extracted from the article]

The association between bilirubin (BIL) and cardiovascular disease (CVD) remains controversial. We performed a meta-analysis of prospective studies to evaluate this association in the general population. We searched PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases through to September 2021. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality. The pooled effect estimate was calculated by the fixed-effect model or random-effect model. We included 12 prospective studies (368 567 participants). The pooled risk ratio of CVD for the lowest vs highest groups of BIL levels was.75 (95% CI:.58-.97) with high heterogeneity (I2 = 87.5%, P <.001). Similar associations were observed for coronary heart disease and stroke. We further performed a "dose-response" meta-analysis, and a significant U-shaped relationship between circulating (most values were serum bilirubin, but a few were plasma bilirubin) BIL and CVD (P <.01) was observed. The lowest risk of CVD events was observed in participants with a BIL of 17-20 µmol/L in serum and/or plasma. In conclusion, there was a U-shaped dose-response relationship between BIL and CVD, especially for men. Further studies are needed to confirm our findings and identify the mechanisms involved as well as any prognostic or therapeutic potential. [ABSTRACT FROM AUTHOR]

This study investigates the preparation of TiO 2 –SiO 2 –CaCO 3 composite opacifier (Ti–Si–Ca) and its application in sanitary ceramic glazes. This approach involved hydrophobic agglomeration through surface-induced hydrophobic modification of TiO 2 , SiO 2 and CaCO 3 particles, along with the interactions between the hydrophobic carbon chains of modifiers. The Ti–Si–Ca formed a uniform coating with well-dispersed TiO 2 and SiO 2 particles on the CaCO 3 surface and strong bonds formed among TiO 2 , SiO 2 and CaCO 3 through interpenetration of the organic carbon chains on the surface. The Ti–Si–Ca was added to the basic glazes of sanitary ceramics at a proportion of 15.5 % and fired at 1125 °C for 4 h. The resulting white ceramic glazes had chromaticity values of L*, a*, and b* at 93.76, −0.73, and 3.89, respectively, demonstrating superior glaze opacity and whiteness compared to glazes made with a ZrSiO 4 opacifier (L* 90.30, b* 4.50). Glass and titanite phase make up the majority of the Ti–Si–Ca ceramic glazing layer of, with titanite serving as the opacified phase. Elimination of organic groups in Ti–Si–Ca during glaze firing formed interfacial chemical bonds among TiO 2 , SiO 2 and CaCO 3 , which facilitated the synthesis of titanite from the three components at high temperatures. The Ti–Si–Ca was a highly opaque glaze without yellowing because the organic groups of Ti–Si–Ca were removed and interfacial chemical bonds formed among the TiO 2 , SiO 2 and CaCO 3 in the low-temperature stage of glaze firing. This transformed the three phases into titanite at high temperature and eliminated free TiO 2. The formation of rutile TiO 2 , which has a yellow hue, at high temperatures was inhibited. This study provides a novel approach for low-energy preparation of TiO 2 –SiO 2 –CaCO 3 composite opacifiers and addresses the challenge of replacing ZrSiO 4 with TiO 2 in ceramic opacifiers. [ABSTRACT FROM AUTHOR]

The Open Geospatial Consortium (OGC) is an international non-profit standards organization. Established in 1994, OGC aims to make geospatial information and services FAIR-Findable, Accessible, Interoperable, and Reusable. OGC specifications have greatly facilitated interoperability among software, hardware, data, and users in the GIS field. This study collected publications related to OGC specifications from the Web of Science (WoS database) between 1994 to 2020 and conducted a literature analysis using Derwent Data Analyzer and VosViewer, finding that OGC specifications have been widely applied in academic fields. The most productive organizations were Wuhan University and George Mason University; the most common keywords were interoperability, data, and web service. Since 2018, the emerging keywords that have attracted much attention from researchers were 3D city models, 3D modeling, and smart cities. To make geospatial data FAIR, the OGC specifications SWE and WMS served more for "Findable", SWE contributed more to "Accessible", WPS and WCS served more for "Interoperable", and WPS, XML schemas, WFS, and WMS served more for "Reusable". The OGC specification also serves data and web services for large-scale infrastructure such as the Digital Earth Platform of the Chinese Academy of Sciences. [ABSTRACT FROM AUTHOR]

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π–π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science. [ABSTRACT FROM AUTHOR]

Here we report on the design, synthesis, and assembly of an enzymatic programmable peptide system inspired by endocytic processes to induce molecular assemblies formation spatiotemporally in living cancer cells, resulting in glioblastoma cell death mainly in necroptosis. Our results indicate the stability and glycosylation of molecules play an essential role in determining the final bioactivity. Detailed mechanistic studies by CLSM, Flow cytometry, western blot, and Bio‐EM suggest the site‐specific formation of assemblies, which could induce the LMP and activate the downstream cell death pathway. Moreover, we also demonstrate that our strategy can boost the activity of commercial chemotherapy drug by escaping lysosome sequestration. We expected this work would be expanded towards artificial intelligent biomaterials for cancer therapy and imaging precisely. [ABSTRACT FROM AUTHOR]

Pyroptosis is a pro-inflammatory form of programmed cell death, whose genesis directly depended on caspase-1 activation. Pulmonary hypertension (PH) is a disease characterized, in part, by vascular fibrosis. Up to now, there is no report on the relationship between pyroptosis and vascular fibrosis in PH. Here, we confirmed that pyroptosis had occurred in the media of pulmonary arteries in two PH rat models and hypoxic human pulmonary arterial smooth muscle cells (hPASMCs). Caspase-1 inhibition attenuated the pathogenesis of PH, as assessed by vascular remodeling, right ventricular systolic pressure, right ventricle hypertrophy and hemodynamic parameters of pulmonary vasculature. Moreover, caspase-1 inhibition suppressed pulmonary vascular fibrosis as demonstrated by Masson staining, as well as immunohistochemistry and Western blot analysis of fibrillar collagen. In addition, Programmed death-ligand 1 (PD-L1) was markedly increased in PH, which was regulated by the transcription factor STAT1. Furthermore, PD-L1 knockdown in hPASMCs repressed the onset of hypoxia-induced pyroptosis and fibrosis. Overall, these data identify a critical STAT1-dependent posttranscriptional modification that promotes PD-L1 expression in the pyroptosis of PASMCs to modulate pulmonary vascular fibrosis and accelerate the progression of PH. • Pyroptosis occurs in PH, via the regulation of pumonary fibrosis, which subsequently promotes the progression of PH. • The discovery of the roles of PD-L1 in pyroptosis of PASMCs and pulmonary fibrosis in PH is significant. • The exact binding regions of STAT1 for the PD-L1 promoter were identified. • Taken together, these findings may have far-reaching implications for the management of PH. [ABSTRACT FROM AUTHOR]

Highlights • Systemic activation analysis of FLiBe has been firstly carried out for the molten salt reactor. • The activation analysis was carried out based on an actual reactor design, TMSR-SF1. • The nuclides for shielding design, occupational exposure and environment have been studied. • The initial impurities and corrosion products during operation have both been considered. Abstract As an excellent material for candidate coolant of the molten salt reactor, the activation of 2LiF-BeF 2 is an important issue and should be concerned. In this paper, the activation of 2LiF-BeF 2 has been analyzed based on a specific Molten Salt Reactor. And combined approaches, Monte Carlo method for neutron transport and extension of the Euler for inventory calculation, have been adopted. The short life nuclides for shielding design, the long-life nuclides for occupational radiation exposure management and 3H, 14C production for environment protection have been studied. [ABSTRACT FROM AUTHOR]

Purpose: Accurate puncture of the renal collecting system is crucial to the success of percutaneous nephrolithotomy and presents a technical challenge for urologists. Here, we introduced the Surgical Approach Visualization and Navigation (SAVN) system, a novel navigation system to assist puncture and reduce intraoperative radiation. Materials and methods: Twenty kidneys of 10 cadavers were randomly divided into two groups for renal calyx puncture. In the control group, traditional fluoroscopy was used for guidance, while SAVN system was used in the experimental group. Puncture duration, number of puncture attempts, total number of intraoperative fluoroscopies, and number of fluoroscopies during the puncture procedure were recorded. Results: The puncture duration was 14.2 ± 2.5 s in SAVN group and 48.3 ± 7.1 s in conventional group (P < 0.05). One puncture attempt was needed for successful puncture in SAVN group, while more than one in conventional group (P = 0.28). The total number of intraoperative fluoroscopies was 3.3 ± 1.0 in SAVN group and 14.5 ± 3.1 in control group (P < 0.05),while the number of fluoroscopies during the puncture procedure was 0 and 11.2 ± 2.4, respectively (P < 0.05). Conclusions: The novel SAVN system has a simplified structure and is easy to use. It can be used to successfully assist with puncture of the renal calyx, thus reducing puncture duration and radiation dose. [ABSTRACT FROM AUTHOR]

Abstract Our study evaluated the synergistic impact of vancomycin and omega-3 fatty acids against osteomyelitis in a Staphylococcus aureus -induced rat model of osteomyelitis. The animals were grouped as follows: sham (group I), osteomyelitis (group II, control), vancomycin (20 mg/kg body weight, group III), omega-3 fatty acids (20 mg/kg body weight, group IV) and vancomycin (20 mg/kg body weight) + omega-3 fatty acids (20 mg/kg body weight) (group V). Lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. The determination of bacterial growth and histopathological analyses were carried out. The lipid peroxidation, GSH, SOD, catalase and Gpx levels recovered to near-normal levels following combined treatment with vancomycin and omega-3 fatty acids. The TNF-α and IL-6 levels were reduced to near-normal levels. Combined supplementation with vancomycin and omega-3 fatty acids significantly reduced bacterial growth in bone and the implanted wire. Furthermore, the bone infection levels and histopathological score were reduced. In summary, combined treatment with vancomycin and omega-3 fatty acids was effective against bacterial growth and bone infection compared to monotherapy with vancomycin or omega-3 fatty acids. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Vancomycin and l -homocarnosine reduced lipid peroxidation and TNF-α & IL-6. • Vancomycin and l -homocarnosine reduced bacterial growth and bone infection. • Vancomycin and l -homocarnosine reduced histopathological score. • Vancomycin and l -homocarnosine increased GSH, Gpx, catalase and SOD. Abstract Osteomyelitis is a well-known bone infection in humans. The primary symptoms are fever, pain, weakness, and redness of the bone. l -Homocarnosine is a bioactive peptide abundant in brain and skeletal muscles. The present study evaluated the synergistic effect of vancomycin and l -homocarnosine against osteomyelitis in the Staphylococcus aureus -induced rat model of osteomyelitis. Animals were classified into the following groups: sham (group I), osteomyelitis (group II, control), vancomycin (25 mg/kg body weight, group III), l -homobrassinolide (25 mg/kg body weight, group IV), and vancomycin (25 mg/kg body weight) + l -homobrassinolide (25 mg/kg body weight) (group V). Lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined. Assessments of bacterial growth and histopathological analyses were carried out. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels with the combined treatment of vancomycin and l -homocarnosine. TNF-α and IL-6 levels were reduced to near normal levels. Combined supplementation of vancomycin and l -homocarnosine reduced bacterial growth in bone and wire. Furthermore, bone infections and histopathological scores were also reduced. In summary, we showed that combined treatment of vancomycin and l -homocarnosine was more effective against bacterial growth and bone infection compared to monotherapy with vancomycin or l -homocarnosine. [ABSTRACT FROM AUTHOR]

Endothelial-to-mesenchymal transition (EndoMT) has been recognized as a major reason for the pulmonary artery remodeling (PAR) in pulmonary artery hypertension (PAH). However, the molecular mechanisms and regulatory pathways involved in the EndoMT remain undefined. In the present study, we have confirmed that EndoMT was occurred in pulmonary arteries of rats induced by hypoxia and monocrotaline and in hypoxic pulmonary artery endothelial cells (PAECs). Moreover, hypoxia increased the expression of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) and decreased the expression of neprilysin (NEP), which contributed to the hypoxia-induced EndoMT of PAECs. Furthermore, a reciprocal regulation of PDGF-B and TGF-β1 induced by decreasing NEP promoted the EndoMT of PAECs under hypoxia, which was a novel molecular mechanism to reveal the EndoMT participating in PAR. More importantly, imatinib, a PDGF receptor antagonist, relieved PAR and EndoMT in PAH rats. Thus, our results identify a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [ABSTRACT FROM AUTHOR]

The far-field distribution is measured by a scientific grade CCD in a single-shot nanosecond-level high power Nd:glass laser system based on a vertical truss structure. The beam-pointing drift of the laser system is analyzed in two methods by calculating the geometric center and the energy centroid of the far-field spots. Results show that the RMS value of the long-term angle drift of the output laser beam is less than 17 μrad. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator activated receptor gamma coactivator 1 α (PGC-1 α ) has been confirmed as a key regulatory factor in pulmonary artery smooth muscle cells to mediate mitochondrial biogenesis and proliferation during hypoxia. However, the functional role of PGC-1 α in hypoxic pulmonary artery endothelial cells (PAECs) still needs to be determined. In the present study, we found a marked elevation in the expression of PGC-1 α under hypoxia, which was predominate in the nucleus of PAECs. This alteration of PGC-1 α showed a significant association with 15-Hydroxyeicosatetraenoic acid (15-HETE), a regulator known to be protective against apoptosis at the concentration of 1 μM. By silencing PGC-1 α , the action against cell viability suppression induced by 15-HETE was blocked, not only in normoxic condition but also in hypoxia-stimulated condition. Likewise, the tendency to reduce TUNEL-positive cells, abnormal nuclei and apoptotic cells in response to 15-HETE was depending on PGC-1 α . Furthermore, 15-HETE and PGC-1 α siRNA caused significant alterations in related mechanisms including caspase activity, mitochondrial membrane potential, and Bcl-2 expression. Taken together, these results provide the first evidence to confirm the importance of PGC-1 α in mediating the protective effect of 15-HETE against apoptosis. Therefore, a clear role of PGC-1 α in hypoxic PAECs is demonstrated, which may be attributed to pulmonary vascular remodeling. [ABSTRACT FROM AUTHOR]

Icariin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanism by which Icariin regulates osteogenic differentiation needs to be further revealed. The viability of BMSCs was assessed by cell counting kit 8 assay. BMSC osteogenic differentiation ability was evaluated by detecting alkaline phosphatase activity and performing alizarin red S staining. The protein levels of osteogenic differentiation-related markers, sirtuin 1 (SIRT1), ubiquitin-specific protease 47 (USP47), and Wnt/β-catenin-related markers were determined using western blot. SIRT1 mRNA level was measured using quantitative real-time PCR. The regulation of USP47 on SIRT1 was confirmed by ubiquitination detection and co-immunoprecipitation analysis. Icariin could promote BMSC osteogenic differentiation. SIRT1 expression was enhanced by Icariin, and its knockdown suppressed Icariin-induced BMSC osteogenic differentiation. Moreover, deubiquitinating enzyme USP47 could stabilize SIRT1 protein expression. Besides, SIRT1 overexpression reversed the inhibiting effect of USP47 knockdown on BMSC osteogenic differentiation, and USP47 knockdown also restrained Icariin-induced BMSC osteogenic differentiation. Additionally, Icariin enhanced the activity of the Wnt/β-catenin pathway by upregulating SIRT1. Icariin facilitated BMSC osteogenic differentiation via the USP47/SIRT1/Wnt/β-catenin pathway., (© 2024 John Wiley & Sons A/S.)

Algal toxins produced by microalgae, such as domoic acid (DA) 1 , have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS) 2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The long-term trends in crude mortality rates (CMRs) and age-standardized mortality rates characterized by Segi's world standard population (ASMRWs) of DMSCT in Pudong New Area (PNA), Shanghai, were evaluated from 1973 to 2019, and the role of demographic and non-demographic factors in the mortality of diseases of the musculoskeletal system and connective tissue (DMSCT) was explored., Methods: The PNA district has the largest population and area in Shanghai. Therefore, the mortality registration system of the PNA district was used to calculate and verify the number of deaths. Then, the Joinpoint Regression Program was used to analyze the time trend of mortality. The difference decomposition method was used to visualize the mortality of population and non-population factors, and GraphPad Prism was used for image visualization., Results: A total of 2260 deaths from DMSCT occurred from 1973 to 2019. The CMR and ASMRW of DMSCT were 2.56/105 person-years and 1.57/105 person-years, respectively. The number of people aged ≥80 (696 deaths) who died of DMSCT was the highest among total deaths, the highest number of years of life lost (YLL) was observed in the 45-59 age group, and the YLL rate in the ≥80 age group was the highest. The CMR and YLL rates of DMSCT showed upward trends in the total population from 1973 to 2019., Conclusion: The CMR and YLL rates of DMSCT showed upward trends in the total population from 1973 to 2019 in PNA, Shanghai, and age was closely related to the occurrence of DMSCT. Similarly, demographic factors played a role in this process., Competing Interests: None., (AJTR Copyright © 2023.)

Synthetic micro/nanomotors have attracted considerable attention due to their promising potential in the field of biomedicine. Despite their great potential, major micromotors require chemical fuels or complex devices to generate external physical fields for propulsion. Therefore, for future practical medical and environmental applications, Mg-based micromotors that exhibit water-powered movement and thus eliminate the need for toxic fuels, and that display optimal biocompatibility and biodegradability, are attracting attention. In this review, we summarized the recent microarchitectural design of Mg-based micromotors for biomedical applications. We also highlight the mechanism for realizing their water-powered motility. Furthermore, recent biomedical and environmental applications of Mg-based micromotors are introduced. We envision that advanced Mg-based micromotors will have a profound impact in biomedicine.

Cells use dynamic self-assembly to construct functional structures for maintaining cellular homeostasis. However, using a natural biological small molecule to mimic this phenomenon remains challenging. This work reports the dynamic microfiber formation of nucleopeptide driven by guanosine triphosphate, the small molecule that controls microtubule polymerization in living cells. Deactivation of GTP by enzyme dissociates the fibers, which could be reactivated by adding GTP. Molecular dynamic simulation unveils the mystery of microfiber formation of GBM-1 and GTP. Moreover, the microfiber formation can also be controlled by diffusion-driven GTP gradients across a semipermeable membrane in bulk conditions and the microfluidic method in the defined droplets. This study provides a new platform to construct dynamic self-assembly materials of molecular building blocks driven by GTP.

Ultrasmall CsPbBr 3 perovskite quantum dots (PQDs) as promising blue-emitting materials are highly desired for full-color display and lighting applications, but their inferior efficiency and poor ambient stability hinder extensive applications. Herein, a "break-and-repair" strategy has been developed to tightly confine monodispersed ultrasmall CsPbBr 3 PQDs in a zeolite. In this strategy, the CsPbBr 3 PQDs are introduced into the zeolite via a high temperature evaporation method, wherein the perovskite precursors break the zeolite framework, and amino acids and silane are then used to fix the damaged framework and lock the perovskite QDs within the matrix. By modulating the synthetic conditions to control the growth of CsPbBr 3 , PQDs with ultrasmall size of 2 nm have been obtained in the zeolite, giving emission centered at 460 nm with a high quantum yield of 76.93%. Strikingly, the PQDs@zeolite composite exhibits water-induced reversible photoluminescence promoted by the coordination between the amino acids and PQDs in a dynamic manner, achieving enhanced water stability (14 days in aqueous solution). This work provides a new perspective for the synthesis of water-stable blue-emitting perovskite composites for potential applications in lighting fields.

Chirality correction, asymmetry, ring-chain tautomerism and hierarchical assemblies are fundamental phenomena in nature. They are geometrically related and may impact the biological roles of a protein or other supermolecules. It is challenging to study those behaviors within an artificial system due to the complexity of displaying these features. Herein, we design an alternating D,L peptide to recreate and validate the naturally occurring chirality inversion prior to cyclization in water. The resulting asymmetrical cyclic peptide containing a 4-imidazolidinone ring provides an excellent platform to study the ring-chain tautomerism, thermostability and dynamic assembly of the nanostructures. Different from traditional cyclic D,L peptides, the formation of 4-imidazolidinone promotes the formation of intertwined nanostructures. Analysis of the nanostructures confirmed the left-handedness, representing chirality induced self-assembly. This proves that a rationally designed peptide can mimic multiple natural phenomena and could promote the development of functional biomaterials, catalysts, antibiotics, and supermolecules., (© 2023 Wiley-VCH GmbH.)

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation corrector C g , and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels., (© 2023. The Author(s).)

In this study, the preparation of covalent polyoxometalate organic frameworks (CPOFs) is introduced using the idea of polyoxometalate and covalent organic frameworks. Firstly, the prepared polyoxometalate was functionalized with an amine group (NH 2 -POM-NH 2 ), and then the CPOFs were prepared by a solvothermal Schiff base reaction with NH 2 -POM-NH 2 and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (Tp) as monomers. After the incorporation of PtNPs and MWCNTs into the CPOFs material, the PtNPs-CPOFs-MWCNTs nanocomposites, which possess excellent catalytic activity and electrical conductivity, were formed and utilized as new electrode materials for the electrochemical thymol sensors. The obtained PtNPs-CPOFs-MWCNTs composite exhibits excellent activity toward thymol, which is attributable to its large special surface area, good conductivity and the synergistic catalysis of each component. Under optimal experimental conditions, the sensor presented a good electrochemical response to thymol. The sensor shows two good linear relationships between the current and thymol concentration in the range of 2-65 μM (R 2 = 0.996) and 65-810 μM (R 2 = 0.997), with the corresponding sensitivity of 72.7 μA mM -1 and 30.5 μA mM -1 , respectively. Additionally, the limit of detection (LOD) was calculated to be 0.2 μM (S/N = 3). At the same time, the prepared thymol electrochemical sensor revealed superior stability and selectivity. The constructed PtNPs-CPOFs-MWCNT electrochemical sensor is the first example of thymol detection.

Luminescence multiplexing shows promising application prospects in information security, yet even outstanding time division multiplexing can only carry limited luminescence information. Time-space division multiplexing can greatly expand the information capacity by simultaneously transferring luminescence information in both time and space dimensions. Herein, time-dependent polychrome stereoscopic luminescence system has been successfully developed by designing a 3D luminescence system based on resonance energy transfer (RET), in which afterglow lifetime easily regulated carbon dots-in-zeolite composites are used as energy donors and multicolor fluorescence quantum dots (QDs) as energy acceptors. Taking perovskite QDs (PeQDs) as example, by matching the energy donors with different afterglow lifetimes and the energy acceptors with different fluorescence colors, tunable afterglow emission of PeQDs with wavelength within 463-614 nm and lifetime within 232-1500 ms can be realized, in which the maximal RET efficiency reaches 95%. As a proof of concept, such novel luminescence system that carries eight layers of luminescence information involving four dimensions (time and 3D space) is successfully applied in advanced time-space division multiplexing. This work opens a new perspective for the application of time-space integrated luminescence systems in advanced information multiplexing., (© 2022 Wiley-VCH GmbH.)

Osteoporosis is described as an age-associated impairment of bone formation. microRNA (miR)-29b-3p was thought to be linked to osteoblast differentiation; however, the underlying molecular pathways are yet unknown. The study's goal was to look into the involvement of miR-29b-3p in osteoporosis and the pathophysiological mechanisms. A murine model of estrogen deficiency-induced bone loss was established to simulate postmenopausal osteoporosis. Reverse transcription-quantitative PCR (RT-qPCR) was performed to assess the level of miR-29b-3p of bone tissue. Additionally, miR-29b-3p/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor γ (PPARγ) axis in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was examined. Osteogenesis-related markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2), were assessed at protein and molecular levels. ALP staining and Alizarin Red staining were used to detect ALP activity and calcium deposition. The ovariectomy group was shown to express miR-29b-3p at higher levels in vitro, and miR-29b-3p mimics suppressed osteogenic differentiation and protein/mRNA expression levels of osteogenesis-related markers in vivo. SIRT1 was identified as a target of miR-29b-3p using luciferase reporter assays. Overexpression of SIRT1 reduced the inhibition of osteogenic differentiation by miR-29b-3p. Rosiglitazone, an activator of PPARγ signaling, was able to reverse the downregulation of the osteogenic differentiation of BMSCs and the protein expression of PPARγ caused by miR-29b-3p inhibitors. The results revealed that osteogenesis was suppressed by miR-29b-3p, which blocks the SIRT1/PPARγ axis. These results suggested that postmenopausal osteoporosis could be treated by targeting miR-29b-3p SIRT1/PPARγ., (© 2023. The Society for In Vitro Biology.)

With the economic development and industrialization, the increasingly accumulated tailings ponds in China have become a great risk. Due to the difficulty of selecting proper site for a new reservoir in Yunnan, a sub-dam was built at the downstream original reservoir. This study explored the fracture development and progressive failure characteristics of the tailings reservoir area after capacity expansion based on a similarity experiment and the numerical simulation. The results showed that the primary cracks in the reservoir area were more than those at the top of the sub-dam. With the increase of the upper load, the primary cracks further developed and penetrated the whole sub-dam top, and the sub-cracks were then produced under the concentrate stress of the primary cracks. After the further development of the sub-cracks, the secondary cracks parallel to the primary cracks were formed on the outer slope of the sub-dam. The progressive failure of a tailings dam can be summarized as: the maximum shear stress was firstly generated at the toe of the slope or the top of the dam which then extended to the top of the sub-dam in the form of a curve and finally formed the failure surface by connecting with the primary fracture of the tensile plastic zone at the top of the dam. The study also found that in the process of tailings accumulation in the new reservoir area, tailings would form "back pressure slope protection" at the initial dam of the original reservoir, which not only effectively delayed the occurrence of shear failure, but also inhibited the generation and penetration of tensile plastic zone., (© 2022. The Author(s).)

Objectives: This study sought to identify the epidemiological investigation challenges of the COVID-19 pandemic and offer insights into the underlying issues., Design: An exploratory qualitative study used thematic analysis of semistructured and in-depth individual interviews., Setting: This study was conducted in Centers for Disease Control and Prevention in Guangdong Province., Participants: Twenty-four participants consented to participate in an in-depth interview. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis., Results: The qualitative analysis revealed five key themes: high-intensity epidemiological investigation task, emergency management requiring improvement in the early stage, respondent uncertainty, impact on work and social life and inadequate early-stage Joint Prevention and Control Mechanism., Conclusion: This survey focuses on the epidemiology workforce at the forefront of the COVID-19 pandemic and qualitatively describes their experiences, vocational issues and psychological stressors. We found that the problems of epidemiological investigation posed intense challenges to the epidemiology workforce. These findings highlight the epidemiological investigation challenges associated with this pandemic. We have provided some suggestions that may help improve the efficiency and quality of the epidemiology workforce in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The toxicity effects of paclitaxel (PTX)-loaded magnetic neutrophil-hybrid swimming microrobots ("neutrobots") in vivo were assessed after intravenous administration to mice. The mice after 72 hours exhibited minimal immunotoxicity and liver and kidney toxicity at an administration dose of 3 × 10 6 PTX-loaded neutrobots. The minor toxicity of drug-loaded neutrobots holds considerable promise for biomedical applications.

Controlling the enzymatic reaction of macromolecules in living systems plays an essential role in determining the biological functions, which remains challenging in the synthetic system. This work shows that host-guest complexation could be an efficient strategy to tune the enzymatic self-assembly of the peptide. The formed host-guest complexation prevents the enzymatic kinetics of peptide assemblies on the cell surface and promotes cellular uptake of assemblies. For uptake inside cells, the host-guest complex undergoes dissociation in the acidic lysosome, and the released peptide further self-assembles inside the mitochondria. Accumulating assemblies at mitochondria induce the ferroptosis of cancer cells, resulting in cancer cell death in vitro and the tumor-bearing mice model. As the first example of using host-guest complexation to modulate the kinetics of enzymatic self-assembly, this work provides a general method to control enzymatic self-assembly in living cells for selective programming cancer cell death.

Long noncoding RNAs (lncRNAs) are dysregulated in many cancers. Here, we identified the molecular mechanisms of lncRNA Cancer Susceptibility Candidate 8 (CASC8) in promoting the malignancy of esophageal squamous cell carcinoma (ESCC). CASC8 was highly overexpressed in ESCC tissues and upregulation of CASC8 predicted poor prognosis in ESCC patients. Moreover, CASC8 decreased the cisplatin sensitivity of ESCC cells and promoted ESCC tumor growth in vivo . Mechanistically, CASC8 interacted with heterogeneous nuclear ribonucleoprotein L (hnRNPL) and inhibited its polyubiquitination and proteasomal degradation, thus stabilizing hnRNPL protein levels and activating the Bcl2/caspase3 pathway. Additionally, AlkB Homolog 5, RNA demethylase (ALKBH5)-mediated m6A demethylation stabilized the CASC8 transcript, resulting in CASC8 upregulation. Taken together, these findings identified an oncogenic function of CASC8 in the progression of ESCC, which suggest that CASC8 might become a potential prognostic biomarker in ESCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Hip tumors often require tumor-type artificial joint replacement. The selection of the prosthesis stem (hip tumor prosthesis stem) implantation angle during the operation is important to prevent the complication of postoperative prosthesis dislocation. The aim of this study was to evaluate the role of a nickel-titanium (Ni-Ti) shape memory alloy embracing fixator in determination of the implantation angle of a hip tumor prosthesis stem and analyze its efficacy., Methods: 36 patients with proximal femur tumor were treated with extended tumor resection and prosthetic replacement. 14 patients received prosthetic replacements with the embracing fixators fixing between the junction of the prosthesis stem and the femur temporarily, while the other 22 patients received the same replacements but without the fixators. The two groups were compared regarding occurrence of complications, limb function, and active hip range of motion (ROM)., Results: There was no case of hip dislocation in the group that received prosthetic replacements with the use of embracing fixators. Occurrence of deep infection had no difference between the two groups. However, better limb function and higher active (ROM) on abduction or flexion were observed in the group using embracing fixators., Conclusion: Ni-Ti shape memory alloy embracing fixator plays a key role in assisting the accurate implantation angle of the prosthesis stem in prosthetic replacement. The prosthesis stem can be adjusted to the optimal angle with the help of the embracing fixator. Patients have a lower risk of dislocation, better limb function, and higher active hip ROM., Competing Interests: None., (AJTR Copyright © 2022.)

Flexible biosensors have received intensive attention for real-time, non-invasive monitoring of cancer biomarkers. Highly sensitive tyrosinase biosensors, which are important for melanoma screening, remained a hurdle. Herein, high-performance tyrosinase-sensing field-effect transistor-based biosensors (bio-FETs) have been successfully achieved by self-assembling nanostructured tetrapeptide tryptophan-valine-phenylalanine-tyrosine (WVFY) on n-type metal oxide transistors. In the presence of target tyrosinase, the phenolic hydroxyl groups in WVFY are rapidly converted to benzoquinone with the consumption of protons, which could be detected potentiometrically by bio-FETs. As a result, the WVFY-modified bio-FETs exhibited an ultra-low detection limit of 1.9 fM and an optimal detection range of 10 fM to 1 nM toward tyrosinase sensing. Furthermore, flexible devices fabricated on ∼2.9-μm-thick polyimide (PI) substrates illustrated robust mechanical flexibility, which could be attached to human skin conformally. These achievements hold promise for wearable melanoma screening and provide designing guidelines for detecting other important cancer biomarkers with bio-FETs., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Vaccine hesitancy is a major obstacle to the achievement of universal child vaccination, which has been studied extensively in Western countries but much less so in Asian countries, especially China. This cross-sectional survey is aimed to assess the prevalence of vaccine hesitancy and to explore the reasons for vaccine hesitancy among parents in Guangzhou. In January 2020, a questionnaire adapted to the Chinese setting from a widely-used hesitancy scale was administered to a sample of parents who brought their children aged <13 years to Community Health Service Centers for vaccination in Guangzhou. The incidence of vaccine hesitancy among those parents was 6.6% (50/755). Regression analysis showed that differences in socio-economic characteristics were not associated with the occurrence of vaccine hesitancy among parents in Guangzhou. However, strong distrust of domestic vaccine quality (OR = 10.9, 95% CI = 1.5-81.4), being required to have their children vaccinated for nursery and school entry (OR = 3.6, 95% CI = 1.7-7.7), and not being aware of which vaccines are officially required and which are optional (OR = 2.1, 95% CI = 1.1-4.3) were the risk factors significantly associated with vaccine hesitancy. In order to increase parents' trust in domestic vaccine quality and reduce the prevalence of vaccine hesitancy, it is essential to strengthen quality control in domestic vaccine manufacturing and to proactively disseminate clear and accurate information about vaccines to parents. Furthermore, advocating the value of vaccination among all citizens of Guangzhou is crucial.

Background: Evading immune surveillance is necessary for tumor metastasis. Thus, there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion. In this study, we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma (ESCC)., Methods: The expression of melanoma-associated antigen C3 (MAGE-C3) was detected using immunohistochemistry. Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma (ESCC) cells. Metastasis assays in mice were used to evaluate metastatic ability in vivo. Lymphocyte-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells. RNA sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control cells. Gene ontology (GO) enrichment analyses was performed to identify the most altered pathways influenced by MAGE-C3. The activation of the interferon-γ (IFN-γ) pathway was analyzed using Western blotting, GAS luciferase reporter assays, immunofluorescence, and flow cytometry. The role of MAGE-C3 in the IFN-γ pathway was determined by Western blotting and immunoprecipitation. Furthermore, immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases., Results: MAGE-C3 was overexpressed in ESCC tissues. High expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC. Functional experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition (EMT). MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells, implying an immunosuppressive function. Mechanistically, MAGE-C3 facilitated IFN-γ signaling and upregulated programmed cell death ligand 1 (PD-L1) by binding with IFN-γ receptor 1 (IFNGR1) and strengthening the interaction between IFNGR1 and signal transducer and activator of transcription 1 (STAT1). Interestingly, MAGE-C3 displayed higher tumorigenesis in immune-competent mice than in immune-deficient nude mice, confirming the immunosuppressive role of MAGE-C3. Furthermore, mice bearing MAGE-C3-overexpressing tumors showed worse survival and more lung metastases with decreased CD8 + infiltrated T cells and increased programmed cell death 1 (PD-1) + CD8 + infiltrated T cells., Conclusion: MAGE-C3 enhances tumor metastasis through promoting EMT and protecting tumors from immune surveillance, and could be a potential prognostic marker and therapeutic target., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Multilevel luminescence materials have aroused wide attention for their advanced anti-counterfeiting abilities. However, various complicated stimuli factors involved in multilevel luminescence anti-counterfeiting (MlLA) limit the practical applications of such materials. Herein, carbon dots (CDs) are in situ introduced into Eu-substituted AlPO 4 -5 zeolite (named CDs@EuAPO-5) via a solvent-free thermal crystallization method, which exhibits triple emissions including pink fluorescence mainly associated with Eu 3+ in the zeolite framework, blue fluorescence and green room temperature phosphorescence (RTP) associated with CDs. CDs are uniformly embedded in the EuAPO-5 zeolite matrix. Such composite displays excellent photo-, thermo-, and solvent resistance, as well as long-term storage-stability. Moreover, the triple emissions of the composite only need two kinds of common excitation lights to trigger, without involving other complicated stimuli. A triple-level luminescence anti-counterfeiting (TlLA) label has been built, realizing facile, quick, and advanced luminescence anti-counterfeiting that is hard to copy., (© 2021 Wiley-VCH GmbH.)

Background: Collagen metabolism, controlled by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), might be related to inguinal hernia formation. It was reported that the incidence of inguinal hernia and the recurrence rate after inguinal hernia repair were higher in the elderly. The objective of the research was to assess the amounts of MMP-2 and TIMP-2 in patients at different ages in order to examine the relationship between age and inguinal hernia occurrence., Methods: The research included 40 primary inguinal hernia male patients, and four groups were created: 50-59 years old (A group); 60-69 years old (B group); 70-79 years old (C group); 80-89 years old (D group). We got the samples from anterior rectus sheath fascia. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry were applied to estimate the levels of MMP-2 and TIMP-2., Results: The MMP-2 amounts in C and D group were statistically higher than control group (P < 0.05), and the TIMP-2 levels in C and D group were statistically lower than control group (P < 0.05). We found a positive correlation between age and expression levels of MMP-2 (r = 0.537, P < 0.001; r = 0.569, P < 0.001) and a negative correlation between age and TIMP-2 in inguinal hernia patients (r = - 0.759, P < 0.001; r = - 0.759, P < 0.001)., Conclusions: Increased MMP-2 and reduced TIMP-2 may have some relationships with higher inguinal hernia incidence of the elderly., (© 2021. Société Internationale de Chirurgie.)

Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot ("neutrobot") that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Long non-coding RNAs (lncRNAs) have been found to be involved in the development of many cancers. In this study, we aimed to identify the molecular mechanisms of lncRNA BAALC antisense RNA 1 (BAALC-AS1) in regulating the malignancy of esophageal squamous cell carcinoma (ESCC)., Methods: The expression of BAALC-AS1 in cancer patients was analyzed using a tissue microarray. The protein and RNA levels of BAALC-AS1 were determined by Western blotting analysis and quantitative reverse transcription-PCR (RT-qPCR), respectively. The cell proliferation was determined by cell viability assays, bromodeoxyuridine incorporation, and flow cytometry. The relationships among BAALC-AS1, RasGAPSH3 domain-binding protein 2 (G3BP2), and c-Myc were determined using RNA immunoprecipitation, RNA pull-down assays, and luciferase assays., Results: The expression of BAALC-AS1 was highly up-regulated and associated with malignant phenotypes in ESCC tissues and cell lines. In vivo and in vitro assays showed that BAALC-AS1 promoted ESCC cell proliferation, migration, and invasion. BAALC-AS1 directly interacted with G3BP2, and thereby inhibited the degradation of c-Myc RNA 3'-UTR by G3BP2, thus leading to the accumulation of c-Myc expression. Additionally, c-Myc acted as a transcription factor that can induce the expression of BAALC-AS1 by directly binding to its promoter region., Conclusions: BAALC-AS1/G3BP2/c-Myc feedback loop plays a critical role in the development of ESCC, which might provide a novel therapeutic target and facilitate the development of new therapeutic strategies for the treatment of ESCC., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity., (© 2021 The Author(s).)

We report the reconfigurable assembly of rod-shaped eutectic gallium-indium alloy (EGaIn) liquid metal colloidal motors by mimicking the growth behavior of a dandelion. EGaIn nanorods with a diameter of 210 nm and a length of 850 nm were synthesized via an ultrasound-assisted physical dispersion method. The nanorods possess a core-shell structure with a 30 nm GaOOH shell and zero-valent liquid core. The EGaIn motors move autonomously at a speed of 41.2 μm s -1 under an acoustic field. By modulating the frequency of the applied acoustic field, the EGaIn colloidal motors self-organize into various striped and circular patterns, followed by a flower-like cluster. The dandelion-like EGaIn colloidal motor clusters move collectively and redisperse when the applied acoustic frequency is changed. Numerical simulations reveal that the flower-like clusters are created by the acoustic propulsion in combination with steric repulsion and hydrodynamics., (© 2020 Wiley‐VCH GmbH.)

Carbon dots (CDs) are emerging as a new class of carbon nanomaterials, which have inspired growing interest for their widespread applications in anti-counterfeiting, sensing, bioimaging, optoelectronic and energy-related fields. In terms of the concept of host-guest assembly, immobilizing CDs into porous materials (PMs) has proven to be an effective strategy to avoid the aggregation of bare CDs in solid state, in particular, the host-guest synergy with both merits of CDs and PMs affords composites promising properties in afterglow and tunable emissions, as well as optimizes their performance in optics, catalysis, and energy storage. This Minireview summarizes the recent progress in the research of CDs@PMs, and highlights synthetic strategies of constructing composites and roles of porous matrices in boosting the applications of CDs in diverse areas. The prospect of future exploration and challenges are proposed for designing advanced CDs-based functional nanocomposite materials., (© 2020 Wiley-VCH GmbH.)

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.