Deciphering the Temporal-Spatial Interactive Heterogeneity of Long Non-Coding RNAs and RNA-Binding Proteins in Living Cells at Single-Cell Resolution.

The investigation of long noncoding RNAs (lncRNAs) and RNA binding proteins (RBPs) interactions in living cell holds great significance for elucidating their critical roles in a variety of biological activities, but limited techniques are available to profile the temporal-spatial dynamic heterogeneity. Here, we introduced a molecular beacon-functionalized nanoneedle array designed for spatially resolved profiling of lncRNA-RBP interactions (Nano-SpatiaLR). A nanoneedle array modified with a molecular beacon is employed to selectively isolate specific intracellular lncRNAs and their associated RBPs without affecting cell viability. The RBPs are then in situ analyzed with a fluorescent labeled antibody and colocalized with lncRNA signals to get a quantitative measurement of their dynamic interactions. Additionally, leveraging the spatial distribution and nanoscale modality of the nanoneedle array, this technique provides the spatial heterogeneity information on cellular lncRNA-RBPs interaction at single cell resolution. In this study, we tracked the temporal-spatial interactive heterogeneity dynamics of lncRNA-RBPs interaction within living cells across different biological progresses. Our findings demonstrated that the interactions between lncRNA HOTAIR and RBPs EZH2 and LSD1 undergo significant changes in response to drug treatments, particularly in tumor cells. Moreover, these interactions become more intensified as tumor cells aggregate during the proliferation process.

Free-form and multi-physical metamaterials with forward conformality-assisted tracing.

Transformation theory, active control and inverse design have been mainstream in creating free-form metamaterials. However, existing frameworks cannot simultaneously satisfy the requirements of isotropic, passive and forward design. Here we propose a forward conformality-assisted tracing method to address the geometric and single-physical-field constraints of conformal transformation. Using a conformal mesh composed of orthogonal streamlines and isotherms (or isothermal surfaces), this method quasi-analytically produces free-form metamaterials using only isotropic media. The geometric nature of this approach allows for universal regulation of both dissipative thermal fields and non-dissipative electromagnetic fields. We experimentally demonstrate free-form thermal cloaking in both two and three dimensions. Additionally, the multi-physical functionalities of our method, including optical cloaking, bending and thermo-electric transparency, confirm its broad applicability. Our method features improvements in efficiency, accuracy and adaptability over previous approaches. This study provides an effective method for designing complex metamaterials with arbitrary shapes across various physical domains.

Diagnostic efficacy of virtual organ computer-assisted analysis in measuring the volume ratio of subchorionic hematoma with serum progesterone.

BACKGROUND: Subchorionic hematoma (SCH) is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane. SCH can lead to adverse pregnancy outcomes such as miscarriage, preterm birth, and other complications. Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes. AIM: To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis (VOCAL) in measuring the volume ratio of SCH to gestational sac (GS) combined with serum progesterone on early pregnancy outcomes in patients with SCH. METHODS: A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled. All patients were followed up until a gestational age of 20 wk. The parameters of transvaginal two-dimensional ultrasound, including the circumference of SCH (Cs), surface area of SCH (Ss), circumference of GS (Cg), and surface area of GS (Sg), and the parameters of VOCAL with transvaginal three-dimensional ultrasound, including the three-dimensional volume of SCH (3DVs) and GS (3DVg), were recorded. The size of the SCH and its ratio to the GS size (Cs/Cg, Ss/Sg, 3DVs/3DVg) were recorded and compared. RESULTS: Compared with those in the normal pregnancy group, the adverse pregnancy group had higher Cs/Cg, Ss/Sg, and 3DVs/3DVg ratios (P < 0.05). When 3DVs/3DVg was 0.220, the highest predictive performance predicted adverse pregnancy outcomes, resulting in an AUC of 0.767, and the sensitivity, specificity were 70.2%, 75% respectively. VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients, with a high sensitivity of 82.1% and a specificity of 72.1%, which showed a significant difference between AUC. CONCLUSION: VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH, while combined serum progesterone better predicts adverse pregnancy outcomes.

Dexamethasone induces developmental axon damage in the offspring hippocampus by activating miR-210-3p/miR-362-5p to target the aberrant expression of Sonic Hedgehog.

Given the extensive application of dexamethasone in both clinical settings and the livestock industry, human exposure to this drug can occur through various sources and pathways. Prior research has indicated that prenatal exposure to dexamethasone (PDE) heightens the risk of cognitive and emotional disorders in offspring. Axonal development impairment is a frequent pathological underpinning for neuronal dysfunction in these disorders, yet it remains unclear if it plays a role in the neural damage induced by PDE in the offspring. Through RNA-seq and bioinformatics analysis, we found that various signaling pathways related to nervous system development, including axonal development, were altered in the hippocampus of PDE offspring. Among them, the Sonic Hedgehog (SHH) signaling pathway was the most significantly altered and crucial for axonal development. By using miRNA-seq and targeting miRNAs and glucocorticoid receptor (GR) expression, we identified miR-210-3p and miR-362-5p, which can target and suppress SHH expression. Their abnormal high expression was associated with GR activation in PDE fetal rats. Further testing of PDE offspring rats and infant peripheral blood samples exposed to dexamethasone in utero showed that SHH expression was significantly decreased in peripheral blood mononuclear cells (PBMCs) and was positively correlated with SHH expression in the hippocampus and the expression of the axonal development marker growth-associated protein-43. In summary, PDE-induced hippocampal GR-miR-210-3p/miR-362-5p-SHH signaling axis changes lead to axonal developmental damage. SHH expression in PBMCs may reflect axonal developmental damage in PDE offspring and could serve as a warning marker for fetal axonal developmental damage.

Identification and quantification of compounds with Angiotensin-converting enzyme inhibitory activity in licorice by UPLC-MS.

Licorice is a famous medicine-food herb for treating cardiovascular diseases in many compound prescriptions. Angiotensin-converting enzyme (ACE) is a key target of cardiovascular diseases. Despite its significance, there is limited scientific investigation regarding the ACE inhibitory effects of licorice. In this study, we used an activity-guided approach with an aggregation-induced emission (AIE) fluorescent probe to identify compounds with ACE-inhibitory activity in licorice. Nine components of licorice were found to have ACE inhibitory activity, in which 46 compounds were identified by using UPLC-QTOF-MS. Seven active compounds were found in this study. Among them, licochalcone B had best ACE inhibitory activity (IC50 = 0.24 µM). Finally, an UPLC-Q-MS method was established to quantify the five major active compounds in three batches of licorice. The findings of this study offer valuable insights into the potential of licorice as a source of ACE inhibitors and its relevance in the development of related products.

Transformation hydrodynamic metamaterials: Rigorous arguments on form invariance and structural design with spatial variance.

Transformation optics has been a powerful tool to manipulate physical fields if the governing equations in two spaces satisfy a certain form invariance. A recent interest has been applying this method to design hydrodynamic metamaterials described by the Navier-Stokes equations. However, transformation optics may not be applicable to such a general fluid model while especially the rigorous analysis is still absent. In this work, we give a definite criterion of the required form invariance, i.e., metric of one space and its affine connections that appear in curvilinear coordinates can be incorporated into material properties or interpreted by extra physical mechanisms introduced in another space. Based on this criterion, we prove that the Navier-Stokes equations, as well as its simplification in creeping flows (the Stokes equation), cannot be form invariant due to the redundant affine connections from their viscous terms. On the contrary, the creeping flows under the lubrication approximation, saying the classical Hele-Shaw model and its anisotropic counterpart, can retain the form of their governing equations for steady incompressible isothermal Newtonian fluids. Besides, we propose the design of multilayered structures with spatially varying cell depth to mimic the required anisotropic shear viscosity for modulating Hele-Shaw flows. Our results correct previous misunderstandings about the applicability of transformation optics under the Navier-Stokes equations, reveal the decisive role of lubrication approximation in maintaining form invariance (consistent with recent experiments featuring shallow configurations), and provide a feasible approach in experimental fabrication.

Symmetry-Broken Intermolecular Charge Separation of Cationic Radicals.

A quadrupolar compound Pyr-BA with two pyrrole-type nitrogen atoms doped externally was prepared in this work. In high contrast with other π ionic radicals, its cationic radical Pyr-BA⋅+ undergoes unusual symmetry-broken charge separation (SB-CS), generating the mixed valence complex of Pyr-BA+1-q ⋅⋅⋅Pyr-BA+1+q , where q is the degree of charge transfer. Variable-temperature (VT) single-crystal analysis, absorption and EPR experiments all confirmed that aggregation and lower temperature would help to facilitate this SB-CS process. Gibbs energy calculations and gauge-including magnetically induced current simulation both validate that, for Pyr-BA⋅+ , SB-CS behavior is more favorable than the conventional dimerization mode. To the best of our knowledge, this is the first study that shows solid single-crystal evidence for spontaneous SB-CS between identical ionic radicals. Such a unique phenomenon is of great significance both in terms of fundamental aspects and uncharted material science.

Bowl-Shaped Bispyrrole-Fused Perylene-diimide and Its Anions.

Incorporating two pyrrole subunits at the bay positions of perylene-diimide has been a long-pursued goal since 2009, but it has not been achieved due to high strain. Herein, via one step Buchwald-Hartwig reaction, PDI-2N was successfully generated with a bowl depth of 1.52 Å. Though with electron-rich pyrrole embedding, PDI-2N's radical anion and dianion were facilely prepared and were investigated both experimentally and theoretically. Moreover, PDI-2N crystallized in different manners under distinct conditions, and it formed tubular crystals with infinite two-directional columnar stacking under DMF conditions. This finding develops a dream bowl-shaped PDI derivative that holds great promise in organoelectronics.

Tuning Intermolecular Interactions to Enhance the Cyclability of Non-Aqueous, Organic Redox Flow Batteries.

Enhancing the electrochemical stability and reversibility of redox-active organic molecules is crucial to improve the performance of non-aqueous redox flow batteries (RFBs). Compared with the widely adopted strategy of molecular engineering, we show in this study that tuning the intermolecular interaction between the active material with the supporting electrolyte is another feasible way to address the performance of non-aqueous organic RFBs. Combined with theoretical and experimental investigations, the influence of Lewis acidity of the supporting electrolyte cations and anions on the electrochemical stability and reversibility of bipyridine-based anode material is revealed. As a demonstration, a redox flow cell based on 4,4'-bipyridine anolyte and ferrocene catholyte shows greatly enhanced performance by using supporting electrolyte composed of soft Lewis acid and soft Lewis base. This study provides an alternative, yet highly effective way to addressing the cyclability of an organic compound for non-aqueous RFBs.

Multi-Image Encryption Algorithm Based on Cascaded Modulation Chaotic System and Block-Scrambling-Diffusion.

To address the problem of a poor security image encryption algorithm based on a single chaotic map, this paper proposes a cascade modulation chaotic system (CMCS) that can generate multiple chaotic maps. On this basis, a multi-image encryption algorithm with block-scrambling-diffusion is proposed using CMCS. The algorithm makes full use of the features of CMCS to achieve the effect of one encryption at a time for images. Firstly, the key-value associated with the plaintexts is generated using a secure hash algorithm-512 (SHA-512) operation and random sequence, and the three images are fully confused by the double scrambling mechanism. Secondly, the scrambled image is converted into a bit-level matrix, and the pixel values are evenly distributed using the bit-group diffusion. Finally, the non-sequence diffusion of hexadecimal addition and subtraction rules is used to improve the security of the encryption algorithm. Experimental results demonstrate that the encryption algorithm proposed in this paper has a good encryption effect and can resist various attacks.

Effective Design Strategy of Small Bipolar Molecules through Fused Conjugation toward 2.5 V Based Redox Flow Batteries.

Using bipolar redox-active molecules (BRMs) as active materials is a practical way to address electrolyte crossover and resultant unpredictable side reactions in redox-flow batteries. However, the development of BRMs is greatly hindered by difficulties in finding new molecules from limited redox-active moieties and in achieving high cell voltage to compete with existing flow battery chemistries. This study proposes a strategy for design of high-voltage BRMs using fused conjugation that regulates the redox potential of integrated redox-active moieties. As a demonstration, quaternary N and ketone redox moieties are used to construct a new BRM that shows a prominent voltage gap with good electrochemical stability. A symmetrical redox-flow cell based on this molecule exhibits a high voltage of 2.5 V and decent cycling stability. This study provides a general strategy for designing new BRMs that may enrich the cell chemistries of organic redox-flow batteries.

Porphyrin-based supramolecular nanofibres as a dynamic and activatable photosensitiser for photodynamic therapy.

Photodynamic therapy (PDT) represents a promising treatment modality for a range of cancers and other non-malignant diseases due to its non-invasive nature arising from the light-dependent activation. However, PDT has not been the first-line treatment of cancer thus far as a consequence of, among others, the lack of effective transport and activation strategies, and the undesired side effect caused by skin photosensitisation induced by the "always on" photosensitisers. To overcome this "Achilles' heel", we present herein a non-covalent approach to construct a one-component dynamic supramolecular nanophotosensitising system based on a carefully designed porphyrin. The control of the photoactivities of the resulting supramolecular fibres lies in the spatiotemporal control of the monomer-polymer equilibrium. Both the thermodynamics and kinetics of this nanosystem have been carefully studied by different techniques. Moreover, in vitro and in vivo studies have also been performed, showing that these supramolecular aggregates exhibit facile cell internalisation and progressive disassembly after being endocyted by targeted cells, leading to activation of the photosensitising units and eventually cell death and tumour eradication under photoirradiation.

Synthesis and Properties of BN-embedded N-Perylene.

A B-N embedded nitrogen-annulated perylene has been successfully synthesized. The resultant molecule BN-NP is isoelectronic to coronene, but owns a five-membered pyrrole ring. Experiments and DFT calculations indicated that peripheral pyrrole and BN modifications endow BN-NP with various unique properties like bent structure, dual emission, efficient Lewis acidic response, peripheral aromaticity, narrowest energy band gap among all coronene isoelectronic structures and so on.

The percutaneous oval forceps suture-guiding method with anchor nails for Achilles tendon repair.

BACKGROUND: Acute Achilles tendon rupture (AATR) is a common injury of the foot and ankle. So far, the optimal management of AATR remains controversial. The target of the present retrospective study was to describe a new operative technique for percutaneous repair of AATR and evaluate efficacy of the technique. METHODS: In the present study, 32 patients were enrolled with AATR treated with the percutaneous oval forceps suture-guiding method with anchor nails from Jan 2014 to Jan 2017. The operation duration and length of incision were collected. The functional outcomes were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score, Achilles tendon total rupture score (ATRS), range of motion (ROM) of the ankle and plantar flexion strength ratio at the last follow-up. The postoperative sports activity level and complications were also recorded. RESULTS: The mean operation duration and length of incision were 24.5 min and 2.0 cm. Whilst patient reported outcome questionnaires like AOFAS and ATRS showed good results, ROM of the ankle was quite low with only 16.5 degrees. Plantar flexion strength ratio was lower post surgery, as well. As for the postoperative sports activity level: 26/32 cases (81.3%) returned to former sports activity level; 4/32 cases (12.5%) showed a decline in sports activity level; 2/32 cases (6.2%) gave up on sports. The overall complication rate was 6.2%, one sural nerve damage and one fusiform thickening were found in the study. CONCLUSION: The percutaneous oval forceps suture-guiding method with anchor nails is a new considerable surgery method with adequate healing rates and an alternative to existing surgical procedures.

A self-assembled subphthalocyanine-based nanophotosensitiser for photodynamic therapy.

A subphthalocyanine substituted with nine tetra(ethylene glycol) chains on the periphery has been synthesised. This novel amphiphilic and cone-shaped compound can self-assemble in water into spherical nanoparticles with a hydrodynamic diameter of 154 nm. These nanoparticles can be taken up readily by cancer cells and localised predominately in lysosomes where they disassemble gradually, leading to activation in fluorescence emission and, photocytotoxicity, showing IC50 values of as low as 1.2 µM.

On Transformation Form-Invariance in Thermal Convection.

Over the past two decades, effective control of physical fields, such as light fields or acoustics fields, has greatly benefited from transforming media. One of these rapidly growing research areas is transformation thermotics, especially embodied in the thermal conductive and radiative modes. On the other hand, transformation media in thermal convection has seldom been studied due to the complicated governing equations involving both fluid motion and heat transfer terms. The difficulty lies in the robustness of form invariance in the Navier-Stokes equations or their simplified forms under coordinate transformations, which determines whether the transformation operations can be executed on thermal convection to simultaneously regulate the flow and thermal fields. In this work, we show that thermal convection in two-dimensional Hele-Shaw cells keeps form-invariance, while its counterpart in general creeping flows or general laminar flows does not. This conclusion is numerically verified by checking the performances of invisible devices made of transformation media in convective environments. We further exploit multilayered structures constituted of isotropic homogeneous natural materials to realize the anisotropic inhomogeneous properties required for transformation media. Our results clarify the long-term confusion about the validation of the transformation method in thermal convection and provide a rigorous foundation and classical paradigm on inspiring various fascinating metadevices in both thermal and flow fields.

Glutathione-degradable polydopamine nanoparticles as a versatile platform for fabrication of advanced photosensitisers for anticancer therapy.

A series of glutathione (GSH)-responsive polydopamine (PDA) nanoparticles (NPs) were prepared using a disulfide-linked dopamine dimer as starting material, of which the size could be tuned systematically by adjusting the amount of ammonia solution used. Molecules of a phthalocyanine (Pc)-based photosensitiser and an epidermal growth factor receptor (EGFR)-targeting peptide were then sequentially immobilised on the surface of the NPs through coupling with the surface functionalities of PDA. The immobilised Pc molecules in the resulting nanosystem were photodynamically inactive due to the strong self-quenching effect and the quenching by the PDA core. Upon exposure to GSH in phosphate-buffered saline or EGFR-positive cancer cells, namely A549 and A431 cells, the NPs were disassembled through cleavage of the disulfide linkages to release the Pc molecules, thereby restoring their fluorescence emission and singlet oxygen generation. The NPs with the smallest size (ca. 200 nm in diameter) exhibited the highest cellular uptake and high photocytotoxicity with IC50 values as low as 0.05 µM based on Pc. These NPs could also accumulate and be activated in the tumour of A431 tumour-bearing nude mice, lighting up the tumour with fluorescence over a period of 72 h and completely eradicating the tumour through laser irradiation for 10 min (675 nm, 20 J cm-2). The results suggest that these biodegradable and versatile PDA-based NPs can serve as a promising nanoplatform for fabrication of advanced photosensitisers for targeted photodynamic therapy.

Synthesis and Properties of Aza-Ovalene with Six Zigzag Edges.

Ovalene's nitrogenated derivative with all zigzag edges and nitrogen atom doping at the periphery has been developed via one-step nitrogenation of formylbisanthene. Because of nitrogen incorporation, these molecules show greatly decreased highest occupied molecular orbital levels, enhanced intermolecular interactions, and a reversible acid response. Aza-ovalene also exhibits a diatropic ring current along the periphery. This work provides rare examples of all-zigzag-edged N-polycyclic aromatic hydrocarbons.

Reactive oxygen species-responsive polydopamine nanoparticles for targeted and synergistic chemo and photodynamic anticancer therapy.

A thioketal-linked dimer of 3,4-dihydroxy-L-phenylalanine was prepared which underwent self-polymerisation in the presence of doxorubicin (Dox) in an ethanol/water (1 : 4, v/v) mixture with ammonia. The resulting Dox-encapsulated polydopamine (PDA) nanoparticles were further conjugated with molecules of a zinc(II) phthalocyanine (Pc)-based photosensitiser and a peptide containing the heptapeptide QRHKPRE sequence (labelled as QRH) that can target the epidermal growth factor receptor (EGFR) overexpressed in cancer cells. Upon internalisation into these cells through receptor-mediated endocytosis, these nanoparticles labelled as PDA-Dox-Pc-QRH were disassembled gradually via cleavage of the thioketal linkages by the intrinsic intracellular reactive oxygen species (ROS). The stacked Pc molecules were then disaggregated, resulting in activation of their photosensitising property upon irradiation. The ROS generated by the activated Pc promoted further degradation of the nanoparticles and release of Dox, thereby enhancing cell death by synergistic chemo and photodynamic therapy. Systemic injection of PDA-Dox-Pc-QRH into EGFR-overexpressed tumour-bearing nude mice led to targeted delivery to the tumour, and subsequent light irradiation caused complete tumour ablation without inducing notable toxicity.

Characterizing the Conformational Distribution in an Amorphous Film of an Organic Emitter and Its Application in a "Self-Doping" Organic Light-Emitting Diode.

The conformational distribution and mutual interconversion of thermally activated delayed fluorescence (TADF) emitters significantly affect the exciton utilization. However, their influence on the photophysics in amorphous film states is still not known due to the lack of a suitable quantitative analysis method. Herein, we used temperature-dependent time-resolved photoluminescence spectroscopy to quantitatively measure the relative populations of the conformations of a TADF emitter for the first time. We further propose a new concept of "self-doping" for realizing high-efficiency nondoped OLEDs. Interestingly, this "compositionally" pure film actually behaves as a film with a dopant (quasi-equatorial form) in a matrix (quasi-axial form). The concentration-induced quenching that may occur at high concentrations is thus expected to be effectively relieved. The "self-doping" OLED prepared with the newly developed TADF emitter TP2P-PXZ as a neat emitting layer realizes a high maximum external quantum efficiency of 25.4 % and neglectable efficiency roll-off.