Circ_0007432 promotes non-small cell lung cancer progression and macrophage M2 polarization through SRSF1/KLF12 axis.

Circular RNAs (circRNAs) plays critical roles in non-small cell lung cancer (NSCLC) development. Herein, we illustrated the effects of circ_0007432 on malignant features of NSCLC. We found that circ_0007432 played a promoting role in NSCLC progression, lying in accelerating cell viability, migration and invasion of NSCLC cells, promoting M2 macrophage polarization, suppressing cell apoptosis of NSCLC cells, and enhancing tumor growth in vivo. Mechanistically, the interactions among circ_0007432, SRSF1, KLF12, and IL-8 were validated by RNA-binding protein immunoprecipitation (RIP), electrophoretic mobility shift assay (EMSA), RNA pull-down, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assays. Circ_0007432 upregulated KLF12 by recruiting SRSF1. KLF12 facilitated IL-8 expression and release by binding to IL-8 promoter. Furthermore, the role of circ_0007432/SRSF1/KLF12/IL-8 axis in malignant phenotypes of tumor cells or macrophage polarization was investigated using rescue experiments. In conclusion, circ_0007432 bound with SRSF1 to stabilize KLF12 and then promote IL-8 release, thus promoting malignant behaviors of NSCLC cells and M2 macrophage polarization.

Out-of-equilibrium interactions and collective locomotion of colloidal spheres with squirming of nematoelastic multipoles.

Many living and artificial systems show similar emergent behavior and collective motions on different scales, starting from swarms of bacteria to synthetic active particles, herds of mammals, and crowds of people. What all these systems often have in common is that new collective properties like flocking emerge from interactions between individual self-propelled or driven units. Such systems are naturally out-of-equilibrium and propel at the expense of consumed energy. Mimicking nature by making self-propelled or externally driven particles and studying their individual and collective motility may allow for deeper understanding of physical underpinnings behind collective motion of large groups of interacting objects or beings. Here, using a soft matter system of colloids immersed into a liquid crystal, we show that resulting so-called nematoelastic multipoles can be set into a bidirectional locomotion by external oscillating electric fields. Out-of-equilibrium elastic interactions between such colloidal objects lead to collective flock-like behaviors emerging from time-varying elasticity-mediated interactions between externally driven propelling particles. Repulsive elastic interactions in the equilibrium state can be turned into attractive interactions in the out-of-equilibrium state under applied external electric fields. We probe this behavior at different number densities of colloidal particles and show that particles in dense dispersions collectively select the same direction of a coherent motion due to elastic interactions between near neighbors. In our experimentally implemented design, their motion is highly ordered and without clustering or jamming often present in other colloidal transport systems, which is promising for technological and fundamental-science applications, like nano-cargo transport, out-of-equilibrium assembly, and microrobotics.

Field-controlled dynamics of skyrmions and monopoles.

Magnetic monopoles, despite their ongoing experimental search as elementary particles, have inspired the discovery of analogous excitations in condensed matter systems. In chiral condensed matter systems, emergent monopoles are responsible for the onset of transitions between topologically distinct states and phases, such as in the case of transitions from helical and conical phase to A-phase comprising periodic arrays of skyrmions. By combining numerical modeling and optical characterizations, we describe how different geometrical configurations of skyrmions terminating at monopoles can be realized in liquid crystals and liquid crystal ferromagnets. We demonstrate how these complex structures can be effectively manipulated by external magnetic and electric fields. Furthermore, we discuss how our findings may hint at similar dynamics in other physical systems and their potential applications.

Hypochlorite activatable ratiometric fluorescent probe based on endoplasmic reticulum stress for imaging of atherosclerosis.

Endoplasmic reticulum (ER) stress can induce reactive oxygen (ROS) generation which is directly associated with the emergence of atherosclerosis. Foam cells could promote atherogenesis by inducing ER stress. To understand hypochlorite (ClO-) levels in foam cells under ER stress, novel ER-targeted ClO- activatable ratiometric fluorescence probes Rx-NE and Rx-NCE were designed using a classical rhodamine dye and coumarin dye bridge moiety as the fluorescent skeleton. Both Rx-NE and Rx-NCE demonstrated ratiometric detection capabilities for ClO-, with Rx-NCE showing better sensitivity compared to Rx-NE. The probe Rx-NCE could detect the upregulation of ClO- in foam cells under ER stress and clearly outline delineation of the boundary of atherosclerotic plaques by dual-color imaging. Importantly, the hypochlorite-activated ratiometric probe Rx-NCE had been innovatively applied to the distinction of atherosclerotic blood vessels in atherosclerosis-bearing transgenic (tg) (flk1: eGFP) zebrafish. The probe Rx-NCE is of significant value for investigating the pathological role of ER stress and atherosclerotic diseases, as well as offering new insights into the identification of atherosclerosis.

Construction of HPQ-based activatable fluorescent probe for peroxynitrite and its application in ferroptosis and mice model of LPS-induced inflammation.

As one of the important members of reactive oxygen species, ONOO- plays a crucial role in signal transduction, immune response, and other physiological activities. Aberrant changes in ONOO- levels in the living organism are usually associated with many diseases. Therefore, it is important to establish a highly selective and sensitive method for the determination of ONOO- in vivo. Herein, we designed a novel ratio near-infrared fluorescent probe for ONOO- by directly conjugating dicyanoisophorone (DCI) to hydroxyphenyl-quinazolinone (HPQ). Surprisingly, HPQD was unaffected by environmental viscosity and responded rapidly to ONOO- within 40 s. The linear range of ONOO- detection was from 0 µM to 35 µM. Impressively, HPQD did not react with reactive oxygen species and was sensitive to exogenous/endogenous ONOO- in live cells. We also investigated the relationship between ONOO- and ferroptosis and achieved in vivo diagnosis and efficacy evaluation of mice model of LPS-induced inflammation, which showed promising prospects of HPQD in ONOO--related studies.

Repair of fingertip defect with reverse digital artery island flap and repair of donor site with digital dorsal advancement flap.

Objective: The reverse digital artery island flap (RDAF) is widely used in repairing fingertip skin defects based on its good appearance and practicability. However, the donor area of the flap needs skin grafting, which can lead to complications. This retrospective study explored the clinical application of digital dorsal advance flap (DDAF) in repairing the donor site of the reverse digital artery island flap. Method: From June 2019 to February 2022, 17 patients with a soft tissue defect of the finger had been restored with the reverse digital artery island flap, and at the same time, the donor area was repaired with digital dorsal advance flap (DDAF). The sensitivity, the active range of motion (ROM) and patient satisfaction were assessed after the operation. Results: All flaps survived completely without skin grafting with only one linear scar. The sensory and motor functions of all patients recovered well. Assessment based on the Michigan Hand Outcomes Questionnaire (MHQ) showed satisfactory functional recovery for all patients. Conclusions: Reconstruction using RDAF combined with DDAF represents an effective alternative for repairing fingertip skin defects.

Topological steering of light by nematic vortices and analogy to cosmic strings.

Liquid crystals are widely known for their technological uses in displays, electro-optics, photonics and nonlinear optics, but these applications typically rely on defining and switching non-topological spatial patterns of the optical axis. Here, we demonstrate how a liquid crystal's optical axis patterns with singular vortex lines can robustly steer beams of light. External stimuli, including an electric field and light itself, allow us to reconfigure these unusual light-matter interactions. Periodic arrays of vortices obtained by photo-patterning enable the vortex-mediated fission of optical solitons, yielding their lightning-like propagation patterns. Predesigned patterns and spatial trajectories of vortex lines in high-birefringence liquid crystals can steer light into closed loops or even knots. Our vortex lattices might find technological uses in beam steering, telecommunications, virtual reality implementations and anticounterfeiting, as well as possibly offering a model system for probing the interaction of light with defects, including the theoretically predicted, imagination-capturing light-steering action of cosmic strings, elusive defects in cosmology.

Development of an activatable red emissive fluorescent probe for imaging hydrogen disulfide upregulation in living cells and zebrafish.

As a member of reactive sulfur molecules, hydrogen polysulfide (H2Sn) plays a vital role in cell protection, anti-oxidative stress and regulation of redox signaling. The highly selective and sensitive detection of H2Sn was still challenging due to its special nucleophilic and electrophilic reactivity. By incorporating phenyl 2-(benzoylthio) benzoate into semi-naphthofluorescein, we developed a novel red emissive fluorescent probe SNAFL-H2Sn for the detection of a representative H2Sn (e. g. H2S2). The addition of H2S2 would rapidly trigger SNAFL-H2Sn to produce significant turn-on fluorescence signal changes at 626 nm with a linear response over a range of 2-30 µM and a detection limit of 16 nM. SNAFL-H2Sn was capable of mapping exogenous and endogenous H2S2 in living cells and zebrafish. Moreover, SNAFL-H2Sn was applied to detect endogenous H2S2 under atorvastatin stimulation. The present study demonstrated that SNAFL-H2Sn potentially served as a promising tool for interrogating H2Sn functions in biological systems.

Evaluation of nitroreductase activity in nasopharyngeal carcinoma progression by an activatable two-photon fluorescent probe.

Nasopharyngeal carcinoma (NPC) originating from the epithelium cells is the most common malignant tumor of the head and neck. Small-molecule fluorescent probes for early diagnosis of NPC can effectively improve the 5-year survival rate of patients, which makes it become a research hotspot in recent years. Previous studies have suggested the expression levels of NTR in hypoxic tissues or cells and tumors increased relative to the normal state and were positively correlated with the degree of hypoxia. Regarding the mentioned above, we designed a two-photon fluorescent probe NaT-NTR for the detection of NTR in nasopharyngeal cell lines and tissues at different hypoxia levels. NaT-NTR showed high selectivity and sensitivity toward NTR in a complex physiological environment. Furthermore, imaging NTR in different cell lines revealed that the level of intracellular NTR might be positively correlated with the malignancy of nasopharyngeal carcinoma. More importantly, NaT-NTR was successfully applied to detect and image NTR in human nasopharyngeal carcinoma with a penetration depth of 100 µm. On this basis, NaT-NTR might be a powerful chemical tool for the early diagnosis of nasopharyngeal carcinoma.

Construction of a Mitochondria-Endoplasmic Reticulum Dual-Targeted Red-Emitting Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Zebrafish.

Peroxynitrite (ONOO- ) is one of the important reactive oxygen species, which plays a vital role in the physiological process of intracellular redox balance. Revealing the biological functions of ONOO- will contribute to further understanding of the oxidative process of organisms. In this work, we designed and synthesized a novel red-emitting fluorescent probe MCSA for the detection of ONOO- , which could rapidly respond to ONOO- within 250 s and exhibited high sensitivity to ONOO- with a low detection limit of 78 nM. Co-localization experiments demonstrated MCSA had the ability to localize into the mitochondria and endoplasmic reticulum. What's more, MCSA enabled monitoring ONOO- level changes during tunicamycin-induced endoplasmic reticulum stress. We have also successfully achieved the visual detection of exogenous and endogenous ONOO- in living cells and zebrafish. This work presented a chemical tool for imaging ONOO- in vitro and in vivo.

Geometric transformation and three-dimensional hopping of Hopf solitons.

Arising in many branches of physics, Hopf solitons are three-dimensional particle-like field distortions with nontrivial topology described by the Hopf map. Despite their recent discovery in colloids and liquid crystals, the requirement of applied fields or confinement for stability impedes their utility in technological applications. Here we demonstrate stable Hopf solitons in a liquid crystal material without these requirements as a result of enhanced stability by tuning anisotropy of parameters that describe energetic costs of different gradient components in the molecular alignment field. Nevertheless, electric fields allow for inter-transformation of Hopf solitons between different geometric embodiments, as well as for their three-dimensional hopping-like dynamics in response to electric pulses. Numerical modelling reproduces both the equilibrium structure and topology-preserving out-of-equilibrium evolution of the soliton during switching and motions. Our findings may enable myriads of solitonic condensed matter phases and active matter systems, as well as their technological applications.

Construction of a novel electrochemical sensing platform to investigate the effect of temperature on superoxide anions from cells and superoxide dismutase enzyme activity.

It is of great significance to realize the detection of trace amounts of superoxide anions (O2•-) in biological systems due to the connection between the concentration of O2•- and some diseases. Here, we present a novel method to fabricate a non-enzymatic electrochemical sensor for measuring O2•- from biological systems. The sensor was fabricated by nanocomposites (PAMAM-Au) synthesized by using (PAMAM-G4.0) dendrimers as template/stabilizers for gold nanoparticles (AuNPs) growth. Transmission electron microscopy (TEM) investigations indicate that AuNPs were encapsulated in PAMAM with average diameter about 8 nm. The electrochemical technique confirmed that PAMAM-Au possessed extraordinary electrochemical response to superoxide anions. As an analytical and sensing platform, apart from excellent sensitivity, wide liner range (from 3.69 × 10-5 - 37.2 µM), ultra-low detection limit (0.0123 nM), our sensor also presented satisfying performance for monitoring changes of O2•- levels upon different stimuli. Furthermore, we investigated the effect of temperature on superoxide anions released from living cells and enzyme activity through an electrochemical method for the first time. Most importantly, the simulated electrochemical study in vitro further confirmed that temperature has a crucial influence on both the ability of living cells to resist external stimulation and the antioxidant capacity of superoxide dismutase. As expected, the study may provide researchers with potential value for understanding the temperature effects on organisms and the treatment of diseases caused by oxidative stress.

miR-620 regulates radiosensitivity of breast cancer MCF-7 cells by targeting ING4 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨miR-620对乳腺癌MCF-7细胞放射敏感性的影响及其机制。方法：收集2017年3月至2018年3月在海南省儋州市人民医院手术切除的21例乳腺癌患者的癌及癌旁组织标本，以及乳腺癌细胞MCF-7、BCaP-37和乳腺上皮细胞HBL-100，采用qPCR法检测癌组织和细胞中miR-620和生长抑制因子4（ING4）mRNA的表达。利用脂质体转染技术，分别将miR-620抑制剂（anti-miR-620）和抑制剂阴性对照（anti-miR-NC）、anti-miR-620和ING4小干扰RNA（si-ING4）、anti-miR-620和小干扰RNA阴性对照序列（si-NC）转染至MCF-7细胞，经放射处理后（依次记为IR+anti-miR-620组、IR+anti-miR-NC组、IR+anti-miR-620+si-ING4组、IR+anti-miR-620+si-NC组），利用克隆形成实验、MTT法和FCM分别检测细胞放射敏感性、细胞增殖活力、细胞周期分布和凋亡率。双荧光素酶报告基因实验和WB法验证miR-620和ING4的靶向关系。结果：与癌旁组织和HBL-100细胞比较，乳腺癌组织和细胞中miR-620表达均显著升高（均P<0.01）、ING4 mRNA表达均显著降低（均P<0.01）。与IR+anti-miR-NC组比较，IR+anti-miR-620组MCF-7细胞增殖活力、S期细胞比例均显著降低（均P<0.01），细胞凋亡率、G0-G1期细胞比例、放射敏感性均显著升高（均P<0.01）。与IR+anti-miR-620+si-NC组比较，IR+anti-miR-620+si-ING4组MCF-7细胞增殖活力、S期细胞比例均显著升高（均P<0.01），细胞凋亡率、G0-G1期细胞比例和放射敏感性均显著降低（均P<0.01）。双荧光素酶报告基因实验证明ING4是miR-620的靶基因，miR-620靶向负性调控ING4表达。结论：敲减miR-620可能通过上调ING4表达抑制乳腺癌MCF-7细胞增殖，并促进细胞凋亡和放射敏感性。

Metal-Organic Framework-Intercalated Graphene Oxide Membranes for Selective Separation of Uranium.

Design and construction of a membrane that can achieve selective separation of uranium from spent fuel or seawater is a big challenge in the field of separation science. In this work, 1,3,5-benzenetricarboxylic acid (BTC) and three different nitrates (Zn/Ni/Cu) were used to prepare metal-organic frameworks (BTC-MOFs) with different pore sizes, and then, BTC-MOFs were intercalated into the interlayers of graphene oxide (GO) for preparing the composite membranes which presented selective separation of uranium with strong acid resistance. Composite membranes prepared by Zn/Ni/Cu-BTC-MOFs and GO can achieve the separation between ions of different valence states, and their permeability and selectivity depend on the membrane thickness, the acidity of driving solution, and the pore sizes of MOFs. Importantly, Cu-BTC-MOF-intercalated GO membranes can not only achieve the selective separation of Th4+ and UO22+ with a selectivity of ≈6 but also induce the ultra-high selectively separation of UO22+ and Ce3+ because the rejection rate of Ce3+ is about 100%. Moreover, the Zn-BTC-MOF-intercalated GO membrane shows an excellent selectivity of Th4+ and UO22+ with a selectivity of ≈25, and it may also achieve selective separation of uranium from seawater.

UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Thermally reconfigurable monoclinic nematic colloidal fluids.

Fundamental relationships are believed to exist between the symmetries of building blocks and the condensed matter phases that they form1. For example, constituent molecular and colloidal rods and disks impart their uniaxial symmetry onto nematic liquid crystals, such as those used in displays1,2. Low-symmetry organizations could form in mixtures of rods and disks3-5, but entropy tends to phase-separate them at the molecular and colloidal scales, whereas strong elasticity-mediated interactions drive the formation of chains and crystals in nematic colloids6-11. To have a structure with few or no symmetry operations apart from trivial ones has so far been demonstrated to be a property of solids alone1, but not of their fully fluid condensed matter counterparts, even though such symmetries have been considered theoretically12-15 and observed in magnetic colloids16. Here we show that dispersing highly anisotropic charged colloidal disks in a nematic host composed of molecular rods provides a platform for observing many low-symmetry phases. Depending on the temperature, concentration and surface charge of the disks, we find nematic, smectic and columnar organizations with symmetries ranging from uniaxial1,2 to orthorhombic17-21 and monoclinic12-15. With increasing temperature, we observe unusual transitions from less- to more-ordered states and re-entrant22 phases. Most importantly, we demonstrate the presence of reconfigurable monoclinic colloidal nematic order, as well as the possibility of thermal and magnetic control of low-symmetry self-assembly2,23,24. Our experimental findings are supported by theoretical modelling of the colloidal interactions between disks in the nematic host and may provide a route towards realizing many low-symmetry condensed matter phases in systems with building blocks of dissimilar shapes and sizes, as well as their technological applications.

Nitrogen-doped nanoporous graphene induced by a multiple confinement strategy for membrane separation of rare earth.

Rare earth separation is still a major challenge in membrane science. Nitrogen-doped nanoporous graphene (NDNG) is a promising material for membrane separation, but it has not yet been tested for rare earth separation, and it is limited by multi-complex synthesis. Herein, we developed a one-step, facile, and scalable approach to synthesize NDNG with tunable pore size and controlled nitrogen content using confinement combustion. Nanoporous hydrotalcite from Zn(NO3)2 is formed between layers of graphene oxide (GO) absorbed with phenylalanine via confinement growth, thus preparing the sandwich hydrotalcite/phenylalanine/GO composites. Subsequently, area-confinement combustion of hydrotalcite nanopores is used to etch graphene nanopores, and the hydrotalcite interlayer as a closed flat nanoreactor induces two-dimensional space confinement doping of planar nitrogen into graphene. The membrane prepared by NDNG achieves separation of Sc3+ from the other rare earth ions with excellent selectivity (∼3.7) through selective electrostatic interactions of pyrrolic-N, and separation selectivity of ∼1.7 for Tm3+/Sm3+.

Highly Selective Separation of Rare Earth Elements by Zn-BTC Metal-Organic Framework/Nanoporous Graphene via In Situ Green Synthesis.

Rare earth elements (REEs) are used widely in devices of many fields, but it is still a troublesome task to achieve their selective separation and purification. Metal-organic frameworks (MOFs) as an emerging porous crystalline material have been used for selective separation of REEs using the size-selective crystallization properties. However, so far, almost all MOFs cannot be used directly for selective separation of REEs in strong acid via solid-state adsorption. Herein, a zinc-trimesic acid (Zn-BTC) MOF is grown by solid synthesis in situ on ZnO nanoparticles covering nanoporous graphene for preparing Zn-BTC MOF/nanoporous graphene composites with strong acid resistance. The adsorption capacity of the resulting composites to REEs is highly sensitive to the ionic radius, which may be attributed to the fact that the REE ions coordinate with O to form a stable structure. The selectivity of Ce/Lu is ≈10,000, and it is extremely important that the selectivity between adjacent REEs (e.g., Nd/Pr) is as high as ≈9.8, so the composite exhibits the best separation performance so far. This work provides a green, facile, scale, and effective synthesis strategy of Zn-BTC MOF/nanoporous graphene, which is hopefully applied directly in the separation industries of REEs.

TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling.

The interaction between Axin and DVL2 is critical for the breaking down of the beta-catenin destruction complex and the activation of the Wnt/beta-catenin cascade. However, this biological process remains poorly understood. In the present study, TM4SF1 was identified as the interacting partner of DVL2 and positively regulated as Wnt/beta-catenin signalling by strengthening the DVL2-Axin interaction. The expression levels of TM4SF1 were elevated in hepatocellular carcinoma (HCC) and were induced by Kras signalling. The overexpression of TM4SF1 promoted the growth and motility of HCC cells, and up-regulated the target genes (Axin2 and cyclin D1). The down-regulation of TM4SF1 impaired the capability of HCC cells for growth, migration and metastasis. In addition, the down-regulation of TM4SF1 promoted the ubiquitination of beta-catenin. In summary, these results reveal the oncogenic functions of TM4SF1 in HCC progression and suggest that TM4SF1 might be a target for treatment.

Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells.

Accumulating evidence shows that exosomal circRNAs reflect the physiological status of donor cells, and various cell reactions are induced after exosomal circRNAs are captured by recipient cells. In this study, qRT-PCR was performed to detect circ-0004277 expression in hepatocellular carcinoma (HCC) cell lines, tissues, and plasma exosomes. The effects of circ-0004277 on the proliferation and migration of HCC cells were assessed by cell counting, 5-ethynyl-2'-deoxyuridine assays, Transwell migration assays, and tumor formation in nude mice. We found that circ-0004277 was significantly upregulated in HCC cells, tissues, and plasma exosomes compared to that in normal controls. Overexpression of circ-0004277 enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of HCC cells in vivo and in vitro. Furthermore, exosomes from HCC cells enhanced circ-0004277 expression in surrounding normal cells and stimulated EMT progression. ZO-1, a tight junction adapter protein, was downregulated in HCC tissues. In conclusion, our findings suggest that circ-0004277 promotes the malignant phenotype of HCC cells via inhibition of ZO-1 and promotion of EMT progression. In addition, exosomal circ-0004277 from HCC cells stimulates EMT of peripheral cells through cellular communication to further promote the invasion of HCC into normal surrounding tissues.