A lipid metabolism-based prognostic risk model for HBV-related hepatocellular carcinoma.

BACKGROUND: Up to 85% of hepatocellular carcinoma (HCC) cases in China can be attributed to infection of hepatitis B virus (HBV). Lipid metabolism performs important function in hepatocarcinogenesis of HBV-related liver carcinoma. However, limited studies have explored the prognostic role of lipid metabolism in HBV-related HCC. This study established a prognostic model to stratify HBV-related HCC based on lipid metabolisms. METHODS: Based on The Cancer Genome Atlas HBV-related HCC samples, this study selected prognosis-related lipid metabolism genes and established a prognosis risk model by performing uni- and multi-variate Cox regression methods. The final markers used to establish the model were selected through the least absolute shrinkage and selection operator method. Analysis of functional enrichment, immune landscape, and genomic alteration was utilized to investigate the inner molecular mechanism involved in prognosis. RESULTS: The risk model independently stratified HBV-infected patients with liver cancer into two risk groups. The low-risk groups harbored longer survival times (with P < 0.05, log-rank test). TP53, LRP1B, TTN, and DNAH8 mutations and high genomic instability occurred in high-risk groups. Low-risk groups harbored higher CD8 T cell infiltration and BTLA expression. Lipid-metabolism (including "Fatty acid metabolism") and immune pathways were significantly enriched (P < 0.05) in the low-risk groups. CONCLUSIONS: This study established a robust model to stratify HBV-related HCC effectively. Analysis results decode in part the heterogeneity of HBV-related liver cancer and highlight perturbation of lipid metabolism in HBV-related HCC. This study's findings could facilitate patients' clinical classification and give hints for treatment selection.

The relative humidity-dependent viscosity of single quasi aerosol particles and possible implications for atmospheric aerosol chemistry.

Viscosity is a fundamental physicochemical property of aerosol particles that influences chemical evolution, mass transfer rates, particle formation, etc. and also changes with ambient relative humidity (RH). However, the viscosity of real individual aerosol particles still remains less understood. Here, we developed a novel optical system based on dual optical tweezers to measure the viscosity of single suspending aerosol droplets under different RH conditions. In our experiment, a pair of quasi atmospheric aerosol droplets composed of organic and inorganic chemical substances were trapped and levitated by dual laser beams, respectively, and then collided and coalesced. The backscattering light signals and bright-field images of the dynamic coalescence process were recorded to infer the morphological relaxation time and the diameter of the composited droplet. Then, the viscosity of the droplet was calculated based on these measured values. The ambient RH of the aerosol droplets was controlled by varying the relative flow rates of dry and humidified nitrogen gas in a self-developed aerosol chamber. The viscosities of single aqueous droplets nebulized with solutes of sucrose, various sulfates and nitrates, and organic/inorganic mixtures were measured over the atmospheric RH range. Besides, the viscosities of the proxies of actual ambient aerosols in Beijing were investigated, which reasonably interpreted the aerosol chemistry transforming from sulfate dominating to nitrate dominating at the PM10 (particulate matter with an aerodynamic diameter of less than 10 µm) level in the last decade in Beijing. Furthermore, the hygroscopicity of droplets with a solute of organic/inorganic mixtures was researched to obtain a deep insight into the relationship between the viscosity and mass transfer process. Hence, we provide a robust approach for investigating the viscosity and hygroscopicity of the actual individual liquid PM10 aerosols.

Pathways towards Boosting Solar-Driven Hydrogen Evolution of Conjugated Polymers.

Photocatalytic H2 evolution under solar illumination has been considered to be a promising technology for green energy resources. Developing highly efficient photocatalysts for photocatalytic water splitting is long-term desired but still challenging. Conjugated polymers (CPs) have attracted ongoing attention and have been considered to be promising alternatives for solar-driven H2 production due to the excellent merits of the large π-conjugated system, versatile structures, tunable photoelectric properties, and well-defined chemical composites. The excellent merits have offered numerous methods for boosting photocatalytic hydrogen evolution (PHE) of initial CP-based photocatalysts, whose apparent quantum yield is dramatically increased from <1 to >20% in recent five years. According to the photocatalytic mechanism, this review herein systematically summarizes three major strategies for boosting photocatalytic H2 production of CPs: 1) enhancing visible light absorption, 2) suppressing recombination of electron-hole pairs, and 3) boosting surface catalytic reaction, mainly involving eleven methods, that is, copolymerization, modifying cross-linker, constructing a donor-acceptor structure, functionalization, fabricating organic heterojunction, loading cocatalyst, and surface modification. Finally, the perspectives towards the future development of PHE are proposed.

Effect of Topology on Photodynamic Sterilization of Porphyrinic Metal-Organic Frameworks.

Porphyrinic metal-organic frameworks (MOFs) are promising photosensitizers due to the lack of self-aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1 O2 ) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF-525, MOF-545, PCN-223 and PCN-224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1 O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF-545>MOF-525>PCN-224>PCN-223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6 O8 cluster in MOFs greatly affected 1 O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.

A biomechanical analysis of anterior cervical discectomy and fusion alone or combined cervical fixations in treating compression-extension injury with unilateral facet joint fracture: a finite element study.

BACKGROUND: Compression-extension injury with unilateral facet joint fracture is one of the most devastating injuries of subaxial cervical spine. However, it is not yet clear which fixation technique represents the optimal choice in surgical management. This study aims to assess the construct stability at the operative level (C4/C5 cervical spine) following anterior cervical discectomy and fusion (ACDF) alone and combined fixation techniques (posterior-anterior fixations). METHODS: A previously validated three-dimensional C2-T1 finite element model were modified to simulate surgical procedures via the anterior-only approach (ACDF) and combined cervical approach [(transarticular screw, lateral mass screw, unilateral pedicle screw, bilateral pedicle screw) + ACDF, respectively] for treating compression-extension injury with unilateral facet joint fracture at C4/C5 level. Construct stability (range of rotation, axial compression displacement and anterior shear displacement) at the operative level was comparatively analyzed. RESULTS: In comparison with combined fixation techniques, a wider range of motion and a higher maximum von Mises stress was found in single ACDF. There was no obvious difference in range of motion among transarticular screw and other posterior fixations in the presence of anterior fixation. In addition, the screws inserted by transarticular screw technique had high stress concentration at the middle part of the screw but much less than 500 MPa under different conditions. Furthermore, the variability of von Mises stress in the transarticular screw fixation device was significantly lower than ACDF but no obvious difference compared with other posterior fixations. CONCLUSIONS: Of the five fixation techniques, ACDF has proven poor stability and high structural stress. Compared with lateral and pedicle screw, transarticular screw technique was not worse biomechanically and less technically demanding to acquire in clinical practice. Therefore, our study suggested that combined fixation technique (transarticular screw + ACDF) would be a reasonable treatment option to acquire an immediate stabilization in the management of compression-extension injury with unilateral facet joint fracture. However, clinical aspects must also be regarded when choosing a reconstruction method for a specific patient.

Single-Cell Multimodal Analytical Approach by Integrating Raman Optical Tweezers and RNA Sequencing.

Single-cell analysis has become a state-of-art approach to heterogeneity profiling in tumor cells. Herein, we realize a kind of single-cell multimodal analytical approach by combining single-cell RNA sequencing (scRNA-seq) with Raman optical tweezers (ROT), a label-free single-cell identification and isolation technique, and apply it to investigate drug sensitivity. The drug sensitivity of human BGC823 gastric cancer cells toward different drugs, paclitaxel and sodium dichloroacetate, was distinguished in the conjoint analytical way including morphology monitoring, Raman identification, and transcriptomic profiling. Each individual BGC823 cancer cell was measured by Raman spectroscopy, then nondestructively isolated out by ROT, and finally RNA-sequenced. Our results demonstrate each analytical mode can reflect cell response to the drugs from different perspectives and is consistent and complementary with each other. Therefore, we believe the multimodal analytical approach offers an access to comprehensive characterizations of the unicellular complexity, which especially makes sense for studying tumor heterogeneity or a desired special cell from a mixture cell sample such as whole blood.

Rapid and accurate identification of marine microbes with single-cell Raman spectroscopy.

Rapid and accurate identification of individual microorganisms, such as pathogenic or unculturable microbes, is significant in microbiology. In this work, rapid identification of marine microorganisms by single-cell Raman spectroscopy (scRS) using one-dimensional convolutional neural networks (1DCNN) was explored. Here, single-cell Raman spectra of ten species of marine actinomycetes, two species of non-marine actinomycetes and E. coli (as a reference) were individually collected. Several common classification algorithms in chemometrics, including linear discriminant analysis with principal component analysis and a support vector machine, were applied to evaluate the 1DCNN performance based on the raw and pre-processed Raman spectra. 1DCNN showed superior performance on the raw data in terms of its accuracy and recall rate compared with other classification algorithms. Our investigation demonstrated that the scRS-integrating advanced 1DCNN classification algorithm provided a rapid and accurate approach for identifying individual microorganisms without time-consuming cell culture and sophisticated or specific techniques, which could be a useful methodology for discriminating the microbes that cannot be cultured under normal conditions, especially for 'biological risk'-related emergencies.

Weeping candidate genes screened using comparative transcriptomic analysis of weeping and upright progeny in an F1 population of Prunus mume.

Weeping is a specific plant architecture with high ornamental value. Despite the considerable importance of the weeping habit to landscaping applications and knowledge of plant architecture biology, little is known regarding the underlying molecular mechanisms. In this study, growth and phytohormone content were analyzed among the progeny of different branch types in an F1 mapping population of Prunus mume with varying plant architecture. Bulked segregant RNA sequencing was conducted to compare differences among progeny at a transcriptional level. The weeping habit appears to be a complex process regulated by a series of metabolic pathways, with photosynthesis and flavonoid biosynthesis highly enriched in differentially expressed genes between weeping and upright progeny. Based on functional annotation and homologous analyses, we identified 30 candidate genes related to weeping that merit further analysis, including 10 genes related to IAA and GA3 biosynthesis, together with 6 genes related to secondary branch growth. The results of this study will facilitate further studies of the molecular mechanisms underlying the weeping habit in P. mume.

Nondestructive Identification and Accurate Isolation of Single Cells through a Chip with Raman Optical Tweezers.

Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell study such as heterogeneity of tumor and microbial cells. Herein we designed a chip utilizing ROT to isolate a specific single cell. The chip was made from a polydimethylsiloxane (PDMS) slab and formed into a gourd-shaped reservoir with a connected channel on a cover glass. On the chip an individual cell could be isolated from a cell crowd and then extracted with ∼0.5 µL of phosphate-buffered saline (PBS) via pipet immediately after Raman spectral measurements of the same cell. As verification, we separated four different type of cells including BGC823 gastric cancer cells, erythrocytes, lymphocytes, and E. coli cells and quantifiably characterized the heterogeneity of the cancer cells, leukocyte subtype, and erythrocyte status, respectively. The average time of identifying and isolating a specific cell was 3 min. Cell morphology comparison and viability tests showed that the successful rate of single-cell isolation was about 90%. Thus, we believe our platform could further couple other single-cell techniques such as single-cell sequencing and become a multiperspective analytical approach at the level of a single cell.

Effect of taping on posture of thoracic region in patients with thoracic kyphosis using acceleration.

BACKGROUND: In the working environment of modern society, a poor sitting posture for a prolonged time may lead to abnormal spinal alignment such as thoracic kyphosis (TK). OBJECTIVE: This study aimed to evaluate the efficacy of taping for posture correction of patients with TK, providing theoretical and empirical guidance for clinicians attempting to rectify TK posture. METHODS: The study included 15 subjects aged 30-60 years, all with a TK angle of ⩾ 40∘. Subjects were required to ascend and descend a set of three steps (a low step, high step, and second low step) under three different conditions: without tape assistance, with taping assistance using 20% elongation, and with taping assistance using 40% elongation. A triaxial accelerometer was employed to measure and compare the anterior-posterior (AP), vertical (VT), and medial-lateral (MIL) movements of the thoracic vertebrae in the different conditions. RESULTS: There were no significant differences in the MIL (P= 0.903) or AP (P= 0.114) movements between the no tape assistance and 20% elongation taping conditions. However, a significant difference was found in the VT movement (P= 0.017). Comparing the no assistance condition to the 40% elongation taping condition, no significant changes were noted in the MIL movement (P= 0.650), but significant differences were detected in both the VT (P= 0.003) and AP movements (P= 0.016). No significant differences were found in any of the three measurements between 20% and 40% elongation taping. CONCLUSION: Taping serves as an effective method for immediately improving kyphotic posture. It corrects the position of the scapula and cervicothoracic line and exerts passive retraction on the relevant muscles, thus mitigating trunk imbalance.

[Progress of Immunotherapy in EGFR-mutated Advanced Non-small Cell Lung Cancer].

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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Deep brain stimulation (DBS), including optical stimulation and electrical stimulation, has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders. Advances in DBS microsystems based on implantable microelectrode array (MEA) probes have opened up new opportunities for closed-loop DBS (CL-DBS) in situ. This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously. Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems, key challenges, including excessive wired communication, need to be urgently resolved. In this review, we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field. This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

17ß-estradiol biosensors based on different bioreceptors and their applications.

17ß-Estradiol (E2) is a critical sex steroid hormone, which has significant effects on the endocrine systems of both humans and animals. E2 is also believed to play neurotrophic and neuroprotective roles in the brain. Biosensors present a powerful tool to detect E2 because of their small, efficient, and flexible design. Furthermore, Biosensors can quickly and accurately obtain detection results with only a small sampling amount, which greatly meets the detection of the environment, food safety, medicine safety, and human body. This review focuses on previous studies of biosensors for detecting E2 and divides them into non-biometric sensors, enzyme biosensors, antibody biosensors, and aptamer biosensors according to different bioreceptors. The advantages, disadvantages, and design points of various bioreceptors for E2 detection are analyzed and summarized. Additionally, applications of different bioreceptors of E2 detection are presented and highlight the field of environmental monitoring, food and medicine safety, and disease detection in recent years. Finally, the development of E2 detection by biosensor is prospected.

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions.

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

SWCNTs/PEDOT:PSS nanocomposites-modified microelectrode arrays for revealing locking relations between burst and local field potential in cultured cortical networks.

Burst and local field potential (LFP) are fundamental components of brain activity, representing fast and slow rhythms, respectively. Understanding the intricate relationship between burst and LFP is crucial for deciphering the underlying mechanisms of brain dynamics. In this study, we fabricated high-performance microelectrode arrays (MEAs) using the SWCNTs/PEDOT:PSS nanocomposites, which exhibited favorable electrical properties (low impedance: 12.8 ± 2.44 kΩ) and minimal phase delay (-11.96 ± 1.64°). These MEAs enabled precise exploration of the burst-LFP interaction in cultured cortical networks. After a 14-day period of culture, we used the MEAs to monitor electrophysiological activities and revealed a time-locking relationship between burst and LFP, indicating the maturation of the neural network. To further investigate this relationship, we modulated burst firing patterns by treating the neural culture with increasing concentrations of glycine. The results indicated that glycine effectively altered burst firing patterns, with both duration and spike count increasing as the concentration rose. This was accompanied by an enhanced level of time-locking between burst and LFP but a decrease in synchrony among neurons. This study not only highlighted the pivotal role of SWCNTs/PEDOT:PSS-modified MEAs in elucidating the interaction between burst and LFP, bridging the gap between slow and fast brain rhythms in vitro but also provides valuable insights into the potential therapeutic strategies targeting neurological disorders associated with abnormal rhythm generation.

Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations.

The striatum plays a crucial role in studying epilepsy, as it is involved in seizure generation and modulation of brain activity. To explore the complex interplay between the striatum and epilepsy, we engineered advanced microelectrode arrays (MEAs) specifically designed for precise monitoring of striatal electrophysiological activities in rats. These observations were made during and following seizure induction, particularly three and 7 days post-initial modeling. The modification of graphene oxide (GO)/poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)/platinu-m nanoparticles (PtNPs) demonstrated a marked reduction in impedance (10.5 ± 1.1 kΩ), and maintained exceptional stability, with impedance levels remaining consistently low (23 kΩ) even 14 days post-implantation. As seizure intensity escalated, we observed a corresponding increase in neuronal firing rates and local field potential power, with a notable shift towards higher frequency peaks and augmented inter-channel correlation. Significantly, during the grand mal seizures, theta and alpha bands became the dominant frequencies in the local field potential. Compared to the normal group, the spike firing rates on day 3 and 7 post-modeling were significantly higher, accompanied by a decreased firing interval. Power in both delta and theta bands exhibited an increasing trend, correlating with the duration of epilepsy. These findings offer valuable insights into the dynamic processes of striatal neural activity during the initial and latent phases of temporal lobe epilepsy and contribute to our understanding of the neural mechanisms underpinning epilepsy.

Tentacle Microelectrode Arrays Uncover Soft Boundary Neurons in Hippocampal CA1.

Hippocampal CA1 neurons show intense firing at specific spatial locations, modulated by isolated landmarks. However, the impact of real-world scene transitions on neuronal activity remains unclear. Moreover, long-term neural recording during movement challenges device stability. Conventional rigid-based electrodes cause inflammatory responses, restricting recording durations. Inspired by the jellyfish tentacles, the multi-conductive layer ultra-flexible microelectrode arrays (MEAs) are developed. The tentacle MEAs ensure stable recordings during movement, thereby enabling the discovery of soft boundary neurons. The soft boundary neurons demonstrate high-frequency firing that aligns with the boundaries of scene transitions. Furthermore, the localization ability of soft boundary neurons improves with more scene transition boundaries, and their activity decreases when these boundaries are removed. The innovation of ultra-flexible, high-biocompatible tentacle MEAs improves the understanding of neural encoding in spatial cognition. They offer the potential for long-term in vivo recording of neural information, facilitating breakthroughs in the understanding and application of brain spatial navigation mehanisms.

Investigating Communication Dynamics in Neuronal Network using 3D Gold Microelectrode Arrays.

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.

Neuromodulatory Compensation of Cortical Neural Activity on Electrodeposited Pt/Ir Modified Microelectrode Arrays for Temperature Transients.

Temperature has a profound influence on various neuromodulation processes and has emerged as a focal point. However, the effects of acute environmental temperature fluctuations on cultured cortical networks have been inadequately elucidated. To bridge this gap, we have developed a brain-on-a-chip platform integrating cortical networks and electrodeposited Pt/Ir modified microelectrode arrays (MEAs) with 3D-printed bear-shaped triple chambers, facilitating control of temperature transients. This innovative system administers thermal stimuli while concurrently monitoring neuronal activity, including spikes and local field potentials, from 60 microelectrodes (diameter: 30 µm; impedance: 9.34 ± 1.37 kΩ; and phase delay: -45.26 ± 2.85°). Temperature transitions of approximately ±10 °C/s were applied to cortical networks on MEAs via in situ perfusion within the triple chambers. Subsequently, we examined the spatiotemporal dynamics of the brain-on-a-chip under temperature regulation at both the group level (neuronal population) and their interactions (network dynamics) and the individual level (cellular activity). Specifically, we found that after the temperature reduction neurons enhanced the overall information transmission efficiency of the network through synchronous firing to compensate for the decreased efficiency of single-cell level information transmission, in contrast to temperature elevation. By leveraging the integration of high-performance MEAs with perfusion chambers, this investigation provides a comprehensive understanding of the impact of temperature on the spatiotemporal dynamics of neural networks, thereby facilitating future exploration of the intricate interplay between temperature and brain function.

An efficient 3D reconstruction method based on WT-TV denoising for low-dose CT images.

BACKGROUND: In order to reduce the impact of CT radiation, low-dose CT is often used, but low-dose CT will bring more noise, affecting image quality and subsequent 3D reconstruction results. OBJECTIVE: The study presents a reconstruction method based on wavelet transform-total variation (WT-TV) for low-dose CT. METHODS: First, the low-dose CT images were denoised using WT and TV denoising methods. The WT method could preserve the features, and the TV method could preserve the edges and structures. Second, the two sets of denoised images were fused so that the features, edges, and structures could be preserved at the same time. Finally, FBP reconstruction was performed to obtain the final 3D reconstruction result. RESULTS: The results show that The WT-TV method can effectively denoise low-dose CT and improve the clarity and accuracy of 3D reconstruction models. CONCLUSION: Compared with other reconstruction methods, the proposed reconstruction method successfully addressed the issue of low-dose CT noising by further denoising the CT images before reconstruction. The denoising effect of low-dose CT images and the 3D reconstruction model were compared via experiments.