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.

Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

Design of Digital Twin Cutting Experiment System for Shearer.

This study presents an advanced simulated shearer machine cutting experiment system enhanced with digital twin technology. Central to this system is a simulated shearer drum, designed based on similarity theory to accurately mirror the operational dynamics of actual mining cutters. The setup incorporates a modified machining center equipped with sophisticated sensors that monitor various parameters such as cutting states, forces, torque, vibration, temperature, and sound. These sensors are crucial for precisely simulating the shearer cutting actions. The integration of digital twin technology is pivotal, featuring a real-time data management layer, a dynamic simulation mechanism model layer, and an application service layer that facilitates virtual experiments and algorithm refinement. This multifaceted approach allows for in-depth analysis of simulated coal cutting, utilizing sensor data to comprehensively evaluate the shearer's performance. The study also includes tests on simulated coal samples. The system effectively conducts experiments and captures cutting condition signals via the sensors. Through time domain analysis of these signals, gathered while cutting materials of varying strengths, it is determined that the cutting force signal characteristics are particularly distinct. By isolating the cutting force signal as a key feature, the system can effectively distinguish between different cutting modes. This capability provides a robust experimental basis for coal rock identification research, offering significant insights into the nuances of shearer operation.

Integrating Olefin Carboamination and Hofmann-Löffler-Freytag Reaction by Radical Deconstruction of Hydrazonyl N-N Bond.

As a type of elementary organic compounds containing N-N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2-retention and N2-removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2-moiety of hydrazone by a radical facilitated N-N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann-Löffler-Freytag reaction by the reaction of N-homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino-N migration and H-atom transfer. Consequently, a series of structurally significant ϵ-N-sulphonamide-α,α-difluoro-γ-amino acid esters are efficiently produced via continuous C-C bond and dual C-N bonds forging.

Design and Experimental Results of a Three-Dimensional Force Sensor for Shearer Cutting Pick Force Monitoring.

The main focus of this work is the design and development of a three-dimensional force sensor for the cutting pick of a coal mining shearer's simulated drum. This sensor is capable of simultaneously measuring the magnitude of force along three directions of the cutting pick during the cutting sample process. The three-dimensional force sensor is built based on the strain theory of material mechanics, and reasonable structural design is implemented to improve its sensitivity and reduce inter-axis coupling errors. The strain distribution of the sensor is analyzed using finite element analysis software, and the distribution of the strain gauges is determined based on the analysis results. In addition, a calibration test system is designed for the sensor, and the sensitivity, linearity, and inter-axis coupling errors of the sensor are calibrated and tested using loading experiments in three mutually perpendicular directions. Modal simulation analysis and actual cutting pick testing of the coal mining machine's simulated drum are conducted to study the dynamic characteristics and functionality of the sensor in practical applications. The experimental results depict sensitivities of 0.748 mV/V, 2.367 mV/V, and 2.83 mV/V for the newly developed sensor, respectively. Furthermore, the cross-sensitivity error was lower than 5.02%. These findings validate that the sensor's structure satisfies the measurement requirements for pick-cutting forces.

Morphologies of a polyelectrolyte brush grafted onto a cubic colloid in the presence of trivalent ions.

We study the morphologies of a polyelectrolyte brush grafted onto a surface of cubic geometry under good solvent conditions in the presence of trivalent counterions, using molecular dynamics simulations. The electrostatic correlation effect and excluded volume effect on the morphologies are studied through varying the charge fraction and grafting density, respectively. Combining snapshots of surface morphologies, brush height, distribution profiles of polymer monomers, and monomer-monomer/counterion pair correlation functions, it is clearly shown that the electrostatic correlation effect, represented by the trivalent-counterion-mediated bridging effect, can induce lateral microphase separation of the cubic polyelectrolyte brush, resulting in the formation of pinned patches. These structures then lead to multi-scale ordering in the brush system and, thereby, a non-monotonic dependence of the brush height, corresponding to a collapse-to-swell transition, on the grafting density. Our simulation results demonstrate that, with the sequence of surface morphologies responsive to adjusting external parameters, the cubic polyelectrolyte brush can serve as a candidate system for the manufacturing of smart stimuli-responsive materials.

How Implementation of Entropy in Driving Structural Ordering of Nanoparticles Relates to Assembly Kinetics: Insight into Reaction-Induced Interfacial Assembly of Janus Nanoparticles.

The ability to understand and exploit entropic contributions to ordering transition is of essential importance in the design of self-assembling systems with well-controlled structures. However, much less is known about the role of assembly kinetics in entropy-driven phase behaviors. Here, by combining computer simulations and theoretical analysis, we report that the implementation of entropy in driving phase transition significantly depends on the kinetic process in the reaction-induced self-assembly of newly designed nanoparticle systems. In particular, such systems comprise binary Janus nanoparticles at the fluid-fluid interface and undergo phase transition driven by entropy and controlled by the polymerization reaction initiated from the surfaces of just one component of nanoparticles. Our simulations demonstrate that the competition between the reaction rate and the diffusive dynamics of nanoparticles governs the implementation of entropy in driving the phase transition from randomly mixed phase to intercalated phase in these interfacial nanoparticle mixtures, which thereby results in diverse kinetic pathways. At low reaction rates, the transition exhibits abrupt jump in the mixing parameter, in a similar way to first-order, equilibrium phase transition. Increasing the reaction rate diminishes the jumps until the transitions become continuous, behaving as a second-order-like phase transition, where a critical exponent, characterizing the transition, can be identified. We finally develop an analytical model of the blob theory of polymer chains to complement the simulation results and reveal essential scaling laws of the entropy-driven phase behaviors. In effect, our results allow for further opportunities to amplify the entropic contributions to the materials design via kinetic control.

Pressure Sensor with a Color Change at Room Temperature Based on Spin-Crossover Behavior.

Two new iron(II) complexes with 1D chain and 2D network structures have been successfully synthesized and characterized. One of the complexes exhibits a pressure-induced spin-crossover property with a reversible color change from white to purple at room temperature. The special property makes it a suitable candidate as a pressure sensor.

Optimal Reactivity and Improved Self-Healing Capability of Structurally Dynamic Polymers Grafted on Janus Nanoparticles Governed by Chain Stiffness and Spatial Organization.

Structurally dynamic polymers are recognized as a key potential to revolutionize technologies ranging from design of self-healing materials to numerous biomedical applications. Despite intense research in this area, optimizing reactivity and thereby improving self-healing ability at the most fundamental level pose urgent issue for wider applications of such emerging materials. Here, the authors report the first mechanistic investigation of the fundamental principle for the dependence of reactivity and self-healing capabilities on the properties inherent to dynamic polymers by combining large-scale computer simulation, theoretical analysis, and experimental discussion. The results allow to reveal how chain stiffness and spatial organization regulate reactivity of dynamic polymers grafted on Janus nanoparticles and mechanically mediated reaction in their reverse chemistry, and, particularly, identify that semiflexible dynamic polymers possess the optimal reactivity and self-healing ability. The authors also develop an analytical model of blob theory of polymer chains to complement the simulation results and reveal essential scaling laws for optimal reactivity. The findings offer new insights into the physical mechanism in various systems involving reverse/dynamic chemistry. These studies highlight molecular engineering of polymer architecture and intrinsic property as a versatile strategy in control over the structural responses and functionalities of emerging materials with optimized self-healing capabilities.

Light-responsive expansion-contraction of spherical nanoparticle grafted with azopolymers.

Due to the very importance for both fundamental research and technological applications, smart materials with stimuli-responsive properties have been studied intensively. Theoretical investigation contributes to this endeavor through constructing and analyzing a model system which captures main features of the corresponding complex material, wherefrom useful insight can be provided to the trial-and-error experiments. We here report a theoretical study on the smart spherical nanoparticle grafted with light-responsive azobenzene-containing polymers. Utilizing the photoisomerization ability of the azobenzene group, nanoparticles can undergo a light-induced expansion-contraction transition. The wormlike chain based single chain in mean field theory, which has been developed by us recently, is used to investigate this transition in detail. Exploring a large parameter space, our results definitely determine the parameters, including the chain length and effective Kuhn length of grafted chain, nanoparticle radius, grafting density, and position of the azobenzene group along the chain contour, to admit optimum light-responsive behavior of the smart nanoparticle, which provides a guide for experimentalists to design this type of material in a rational manner.

Microphase separation of short wormlike diblock copolymers with a finite interaction range.

We investigate several structural properties of low-molecular weight AB diblock copolymer melts, focusing on a number of features that substantially deviate from those of high-molecular weight copolymer melts. The study is based on the wormlike chain formalism aided by random phase approximation and self-consistent field theory. We examine the effects that stemmed from both the finite molecular weight and the finite interaction range between unlike AB monomers. The latter yields profound effects on systems consisting of short wormlike block copolymers. The noticeable shift of the order-disorder transition point is discussed. Attention is also paid to the strong-segregation regime, where low molecular weight polymers are subject to finite stretchability.

Scaling of polymer dynamics at an oil-water interface in regimes dominated by viscous drag and desorption-mediated flights.

Polymers are found near surfaces and interfaces in a wide range of chemical and biological systems, and the structure and dynamics of adsorbed polymer chains have been the subject of intense interest for decades. While polymer structure is often inferred from dynamic measurements in bulk solution, this approach has proven difficult to implement at interfaces, and the understanding of interfacial polymer conformation remains elusive. Here we used single-molecule tracking to study the interfacial diffusion of isolated poly(ethylene glycol) molecules at oil-water interfaces. Compared to diffusion in dilute aqueous solution, which exhibited the expected dependence of the diffusion coefficient (D) upon molecular weight (M) of D ∼ M(-1/2) for a Gaussian chain, the behavior at the interface was approximately D ∼ M(-2/3), suggesting a significantly more expanded polymer conformation, despite the fact that the oil was a poor solvent for the polymer. Interestingly, this scaling remained virtually unchanged over a wide range of oil viscosity, despite the fact that at low viscosities the magnitude of the diffusion coefficient was consistent with expectations based on viscous drag (i.e., Stokes-Einstein diffusion), and for high viscosity oil, the interfacial mobility was much faster than expected and consistent with the type of intermittent hopping transport observed at the solid-liquid interface. The dependence on molecular weight, in both regimes, was consistent with results from both self-consistent field theory and previous Monte Carlo simulations, suggesting that an adsorbed polymer chain adopted a partially swollen (loop-train-tail) interfacial conformation.

Structure factor of a Gaussian chain confined between two parallel plates.

We study the structure factor of a single Gaussian chain confined between two macroscopic parallel plates theoretically. The chain propagator is constructed in terms of the eigen-spectrum of the Laplace operator under the Dirichlet boundary condition enforced at the two plates, by which the confinement effect enters the treatment through size-dependent eigen-spectrum. In terms of the series expansion solution for the chain propagator, we first calculate the confinement free energy and the confinement force for an arbitrary confinement strength. It is found that the confinement force scales to the distance between the two confining surfaces with a power of -3 for strong confinements and of -2 for weak confinements. Based on the ground state dominance approximation for strong confinements and the Euler-Maclaurin formula for weak confinements, we develop approximation theories for the two limit situations, which agree with the numerical results well. We further calculate the structure factor of the confined Gaussian chain in this slit geometry. While the scattering function of the transverse chain fluctuations perpendicular to the confinement direction is still a Debye function form, the structure factor for the longitudinal fluctuations along the confinement dimension starts with the monotonic Debye function behavior for weak confinements and develops a decaying oscillation behavior with the increase of confinements. The numerical results for the structure factor are also interpreted by developing approximation theories in different confinement regimes. Finally, the orientational average of the anisotropic structure factor is performed and an analytic expression for the averaged structure factor is derived under the ground state dominance approximation for strong confinements.

The study of the structure factor of a wormlike chain in an orientational external field.

A precise representation of the structure factor of a wormlike chain for the arbitrary chain flexibility in an orientational external field is obtained by virtue of the numerical solution to the modified diffusion equation satisfied by the Green's function. The model is built from a standard wormlike chain formalism in a continuous version which crossovers from the rigid-rod limit to the flexible chain limit and the Maier-Saupe interaction which describes the orientational effects from the nematic field. The behaviors of the structure factor in the distinct wavevector k regimes are numerically investigated as functions of chain flexibility and tilt angle between the directors of the nematic field and k. The radius of gyration extracted from the structure factor in small-k regime is also carefully analysed in both the directions along and perpendicular to the nematic axis. Our calculations exactly recover the prediction of the structure factor undergoing an orientational field in the rigid rod limit.

The structure factor of a wormlike chain and the random-phase-approximation solution for the spinodal line of a diblock copolymer melt.

An efficient and convenient numerical approach to calculate the structure factor of a wormlike chain model is proposed by directly dealing with a formal solution of the Green's function. A precise numerical representation of the structure factor of the wormlike chain model is then obtained, for arbitrary chain rigidity. On one hand, in the flexible limit, the numerical results recover the well-known Debye function of the structure factor of a Gaussian chain and furthermore predict the correct large-k behavior that a Gaussian model fails to capture; on the other hand, in the rigid limit, the numerical results recover the well-known Neugebauer function of the structure factor of a rigid rod. Based on the calculated structure factor, the random phase approximation is employed to study the physical properties of the order-disorder transition for asymmetric wormlike diblock copolymers; particularly, the spinodal line of the disordered phase is calculated. For the case of symmetric diblock copolymer microphase separation, the present calculation reproduces the phase boundary previously determined by self-consistent field theories and yields the entire picture crossing over from the flexible-chain limit to the rigid-chain limit.

Nonequilibrium Dynamic Phase Diagram for Transmembrane Transport of Active Particles.

In recent years, there has been considerable push toward the biomedical applications with active particles, which have great potential to revolutionize disease diagnostics and therapy. The direct penetration of active particles through the cell membrane leads to more efficient intracellular delivery than previously considered endocytosis processes but may cause membrane disruption. Understanding fundamental behaviors of cell membranes in response to such extreme impacts by active particles is crucial to develop active particle-based biomedical technologies and manage health and safety issues in this emerging field. Unfortunately, the physical principles underlying the nonequilibrium behaviors from endocytosis to direct penetration remain elusive, and experiments are challenging. Here, we present a computed dynamic phase diagram for transmembrane transport of active particles and identify four characteristic dynamic phases in endocytosis and direct penetration according to the particle activity and membrane tension. The boundaries dividing these phases are analytically obtained with theoretical models, elucidating the nonequilibrium physics and criteria for the transition between different phases. Furthermore, we numerically and experimentally show three distinct dynamic regimes related to the interplay between necking and wrapping during the endocytosis process of active particles, which strikingly contrast the regimes for passive particles. Overall, these findings could be useful for sharpening the understanding of basic principles underlying biological issues related to the safe and efficient biomedical applications of such emerging matters.

The impact of educational lifestyle intervention on body weight and psychological health among overweight/obese patients with severe mental disorders.

BACKGROUND: There was a high prevalence of overweight/obesity among patients with severe mental disorders (SMD). However, studies on the lifestyle-based interventions in patients with SMD are limited. OBJECTIVE: To examine the effects of an educational lifestyle intervention on body weight and psychological health among Chinese community-dwelling overweight/obese patients with SMD. METHODS: Community-dwelling overweight/obese patients with SMD was recruited from Shenzhen, China in October 2020. They were randomly allocated into intervention group (IG) and control group (CG). Participants in IG received a 12-month educational lifestyle intervention, while the CG was exposed to routine care. A generalized estimating equation model was used to assess the effect of the intervention over time. RESULTS: A total of 176 subjects (88 in IG and 88 in CG) aged 42.2 ± 10.9 years were included in this study. After adjusting for potential confounders, body weight (p = 0.001), body mass index (BMI, p = 0.001), and waist circumference (p = 0.027) in IG significantly decreased compared with CG after 12 months. Besides, IG had significantly higher life satisfaction than CG after intervention (p = 0.026), whereas significant reductions in depressive symptoms were observed in IG from 26.1 % at baseline to 13.6 % after the intervention (p = 0.027), and the between-group differences were marginally significant (p = 0.086). CONCLUSION: An educational lifestyle intervention can effectively reduce body weight parameters and improve psychological health in overweight/obese patients with SMD.

Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer.

BACKGROUND: The purpose of this study was to determine whether LAPTM4B over-expression is associated with the prognosis and chemotherapy resistance in patients with stages III and IV epithelial ovarian carcinoma, i.e., patients with peritoneal metastasis or lymph node metastasis of epithelial ovarian carcinoma. METHODS: LAPTM4B expression was evaluated in 10 normal ovarian and 113 stages III-IV ovarian carcinomas specimens by Western blotting analyses and immunohistochemistry. Univariate and multivariate analyses were performed to determine the association between LAPTM4B expression and prognosis and the relationship between LAPTM4B over-expression and chemotherapy resistance. RESULTS: Western blotting analysis demonstrated that LAPTM4B was overexpressed in ovarian cancers, and immunohistochemistry results revealed that 80 patients were LAPTM4B over-expression. The five-year overall survival (OS) rates for patients with high LAPTM4B expression and low LAPTM4B expression were 27.36% and 90.7%, respectively (hazard ratio = 20.611, 95% CI: 5.916-71.808, P < 0.0001). The five-year progression-free survival (PFS) rate was 17.68% for patients in the high-expression group and 84.42% for patients in the low-expression group (hazard ratio = 17.852, 95% CI: 6.31-5.935, P < 0.0001); The presence of chemotherapy resistance was significantly associated with LAPTM4B expression (OR: 36.609, 95% CI: 4.737-282.941, P = 0.0006). CONCLUSIONS: LAPTM4B over-expression is an independent factor in stages III-IV epithelial ovarian carcinoma prognosis and chemotherapy resistance, and it may be an important potential biomarker.

Polymeric Microparticles Generated via Confinement-Free Fluid Instability.

In-fiber fluid instability can be harnessed to realize scalable microparticles fabrication with tunable sizes and multifunctional characteristics making it competitive in comparison to conventional microparticles fabrication methods. However, since in-fiber fluid instability has to be induced via thermal annealing and the resulting microparticles can only be collected after dissolving the fiber cladding, obtaining contamination-free particles for high-temperature incompatible materials remains great challenge. Herein, confinement-free fluid instability is demonstrated to fabricate polymeric microparticles in a facile manner induced by the ultralow surface energy of the superamphiphobic surface. The polymer solution columns break up into uniform droplets then form spherical particles spontaneously in seconds at ambient temperature. This method can be applied to a variety of polymers spanning an exceptionally wide range of sizes: from 1 mm down to 1 µm. With the aid of microfluidic spinning instrument, a large quantity of microparticles can be obtained, making this method promising for scaling up production. Notably, through simple modification of the feed solution configuration, composite/structured micromaterials can also be produced, including quantum-dots-labeled fluorescent particles, magnetic particles, core-shell particles, microcapsules, and necklace-like microfibers. This method, with general applicability and facile control, is envisioned to have great prospects in the field of polymer microprocessing.

Blood pressure circadian rhythms and adverse outcomes in type 2 diabetes patients diagnosed with orthostatic hypotension.

AIMS/INTRODUCTION: Patients with diabetes frequently develop orthostatic hypotension (OH). The present study was designed to examine the relationship of blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. MATERIALS AND METHODS: In the present study, 173 inpatients with type 2 diabetes were enrolled. Patients were divided into an OH group and a non-OH group according to the BP changes detected in the supine and standing position. Then, 24-h ambulatory BP was monitored. Patients were followed up for an average of 45 ± 10 months post-discharge. Outcomes - death and major adverse cardiac and cerebrovascular events, including heart failure, myocardial infarction and stroke - were recorded. RESULTS: There were 61 patients (35.26%) in the OH group and 112 patients (64.74%) in the non-OH group. In the OH group, the night-time systolic BP and night-time diastolic BP were higher, the blood BP rhythms were predominantly of the riser type (67.21%). OH was as an independent marker of riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval 2.579-7.966). In the OH group, the incidence rates of mortality, and major adverse cardiac and cerebrovascular events were increased significantly compared with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P < 0.01). CONCLUSIONS: In patients who had type 2 diabetes diagnosed with OH, the BP circadian rhythm usually showed riser patterns, and they had increased rates of mortality, and major adverse cardiac and cerebrovascular events.