Links Between Cellular Energy Metabolism and Pain Sensation.

One of the functions of organism cells is to maintain energy homeostasis to promote metabolism and adapt to the environment. The 3 major pathways of cellular energy metabolism are glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS). Neurons, astrocytes, and microglia are crucial in allodynia, hyperalgesia, and sensitization in nociceptive pathways. This review focused on these 3 major cellular energy metabolism pathways, aiming to elucidate the relationship between neurocyte and pain sensation and present the reprogramming of energy metabolism on pain, as well as the cellular and molecular mechanism underlying various forms of pain. The clinical and preclinical drugs involved in pain treatment and molecular mechanisms via cellular energy metabolism were also discussed.

Design and Development of Metasurface Materials for Enhancing Photodetector Properties.

Recently, metasurface-based photodetectors (metaphotodetectors) have been developed and applied in various fields. Metasurfaces are artificial materials with unique properties that have emerged over the past decade, and photodetectors are powerful tools used to quantify incident electromagnetic wave information by measuring changes in the conductivity of irradiated materials. Through an efficient microstructural design, metasurfaces can effectively regulate numerous characteristics of electromagnetic waves and have demonstrated unique advantages in various fields, including holographic projection, stealth, biological image enhancement, biological sensing, and energy absorption applications. Photodetectors play a crucial role in military and civilian applications; therefore, efficient photodetectors are essential for optical communications, imaging technology, and spectral analysis. Metaphotodetectors have considerably improved sensitivity and noise-equivalent power and miniaturization over conventional photodetectors. This review summarizes the advantages of metaphotodetectors based on five aspects. Furthermore, the applications of metaphotodetectors in various fields including military and civil applications, are systematically discussed. It highlights the potential future applications and developmental trends of metasurfaces in metaphotodetectors, provides systematic guidance for their development, and establishes metasurfaces as a promising technology.

A dual-labeling fluorescent probe to track lysosomal polarity and endoplasmic reticulum dynamics during ferroptosis.

A polarity-sensitive probe was developed to simultaneously label lysosomes and endoplasmic reticulum (ER) via its dansylamide and rhodamine fluorescence, respectively, enabling ratiometric polarity detection and stable dual-labeling. The fragmented ER network and increased lysosomal polarity during ferroptosis were revealed, which facilitates the understanding of ferroptotic mechanisms.

Comprehensive analysis and identification of subtypes and hub genes of high immune response in lung adenocarcinoma.

BACKGROUND: The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments. METHODS: The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized. RESULTS: Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2. CONCLUSIONS: Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

Development and Application of IoT Monitoring Systems for Typical Large Amusement Facilities.

The advent of internet of things (IoT) technology has ushered in a new dawn for the digital realm, offering innovative avenues for real-time surveillance and assessment of the operational conditions of intricate mechanical systems. Nowadays, mechanical system monitoring technologies are extensively utilized in various sectors, such as rotating and reciprocating machinery, expansive bridges, and intricate aircraft. Nevertheless, in comparison to standard mechanical frameworks, large amusement facilities, which constitute the primary manned electromechanical installations in amusement parks and scenic locales, showcase a myriad of structural designs and multiple failure patterns. The predominant method for fault diagnosis still relies on offline manual evaluations and intermittent testing of vital elements. This practice heavily depends on the inspectors' expertise and proficiency for effective detection. Moreover, periodic inspections cannot provide immediate feedback on the safety status of crucial components, they lack preemptive warnings for potential malfunctions, and fail to elevate safety measures during equipment operation. Hence, developing an equipment monitoring system grounded in IoT technology and sensor networks is paramount, especially considering the structural nuances and risk profiles of large amusement facilities. This study aims to develop customized operational status monitoring sensors and an IoT platform for large roller coasters, encompassing the design and fabrication of sensors and IoT platforms and data acquisition and processing. The ultimate objective is to enable timely warnings when monitoring signals deviate from normal ranges or violate relevant standards, thereby facilitating the prompt identification of potential safety hazards and equipment faults.

Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Retraction Notice to: Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression.

[This retracts the article DOI: 10.1016/j.omtn.2019.07.012.].

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation.

BACKGROUND: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear. AIM: To explore the mechanism of YGS anti-gastric cancer and immune regulation. METHODS: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes. RESULTS: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets. CONCLUSION: YGS has the effect of anti-gastric cancer and immune regulation.

Intelligent wearable olfactory interface for latency-free mixed reality and fast olfactory enhancement.

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.

Pyrene-Alkyne-Based Conjugated Porous Polymers with Skeleton Distortion-Mediated ⋠O2 - and 1O2 Generation for High-Selectivity Organic Photosynthesis.

Reactive oxygen species (ROS) play a crucial role in determining photocatalytic reaction pathways, intermediate species, and product selectivity. However, research on ROS regulation in polymer photocatalysts is still in its early stages. Herein, we successfully achieved series of modulations to the skeleton of Pyrene-alkyne-based (Tetraethynylpyrene (TEPY)) conjugated porous polymers (CPPs) by altering the linkers (1,4-dibromobenzene (BE), 4,4'-dibromobiphenyl (IP), and 3,3'-dibromobiphenyl (BP)). Experiments combined with theoretical calculations indicate that BE-TEPY exhibits a planar structure with minimal exciton binding energy, which favors exciton dissociation followed by charge transfer with adsorbed O2 to produce ⋅O2 -. Thus BE-TEPY shows optimal photocatalytic activity for phenylboronic acid oxidation and [3+2] cycloaddition. Conversely, the skeleton of BP-TEPY is significantly distorted. Its planar conjugation decreases, intersystem crossing (ISC) efficiency increases, which makes it more prone for resonance energy transfer to generate 1O2. Therefore, BP-TEPY displays best photocatalytic activity in [4+2] cycloaddition and thioanisole oxidation. Both above reactant conversion and its product selectivity exceed 99 %. This work systematically reveals the intrinsic structure-activity relationship among the skeleton structure of CPPs, excitonic behavior, and selective generation of ROS, providing new insights for the rational design of highly efficient and selective CPPs photocatalysts.

The binding of PKCε and MEG2 to STAT3 regulates IL-6-mediated microglial hyperalgesia during inflammatory pain.

Studies have suggested that microglial IL-6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL-6-mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t-STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, GLUT3, and TREM2 were assessed by Western blot. IL-6 promoter activity and IL-6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL-6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL-6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL-6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.

Effects of eutrophication on the horizontal transfer of antibiotic resistance genes in microalgal-bacterial symbiotic systems.

Overloading of nutrients such as nitrogen causes eutrophication of freshwater bodies. The spread of antibiotic resistance genes (ARGs) poses a threat to ecosystems. However, studies on the enrichment and spread of ARGs from increased nitrogen loading in algal-bacterial symbiotic systems are limited. In this study, the transfer of extracellular kanamycin resistance (KR) genes from large (RP4) small (pEASY-T1) plasmids into the intracellular and extracellular DNA (iDNA, eDNA) of the inter-algal environment of Chlorella pyrenoidosa was investigated, along with the community structure of free-living (FL) and particle-attached (PA) bacteria under different nitrogen source concentrations (0-2.5 g/L KNO3). The results showed that KR gene abundance in the eDNA adsorbed on solid particles (D-eDNA) increased initially and then decreased with increasing nitrogen concentration, while the opposite was true for the rest of the free eDNA (E-eDNA). Medium nitrogen concentrations promoted the transfer of extracellular KR genes into the iDNA attached to algal microorganisms (A-iDNA), eDNA attached to algae (B-eDNA), and the iDNA of free microorganisms (C-iDNA); high nitrogen contributed to the transfer of KR genes into C-iDNA. The highest percentage of KR genes was found in B-eDNA with RP4 plasmid treatment (66.2%) and in C-iDNA with pEASY-T1 plasmid treatment (86.88%). In addition, dissolved oxygen (DO) significantly affected the bacterial PA and FL community compositions. Nephelometric turbidity units (NTU) reflected the abundance of ARGs in algae. Proteobacteria, Cyanobacteria, Bacteroidota, and Actinobacteriota were the main potential hosts of ARGs. These findings provide new insights into the distribution and dispersal of ARGs in the phytoplankton inter-algal environment.

Mannose modified targeted immersion vaccine delivery system improves protective immunity against Infectious spleen and kidney necrosis virus in mandarin fish (Siniperca chuatsi).

Vaccination is an effective method to prevent viral diseases. However, the biological barrier prevents the immersion vaccine from achieving the best effect without adding adjuvants and carriers. Researches on the targeted presentation technology of vaccines with nanocarriers are helpful to develop immersion vaccines for fish that can break through biological barriers and play an effective role in fish defense. In our study, functionally modified single-walled carbon nanotubes (SWCNTs) were used as carriers to construct a targeted immersion vaccine (SWCNTs-M-MCP) with mannose modified major capsid protein (MCP) to target antigen-presenting cells (APCs), against iridovirus diseases. After bath immunization, our results showed that SWCNTs-M-MCP induced the presentation process and uptake of APCs, triggering a powerful immune response. Moreover, the highest relative percent survival (RPS) was 81.3% in SWCNTs-M-MCP group, which was only 41.5% in SWCNTs-MCP group. Altogether, this study indicates that the SWCNTs-based targeted immersion vaccine induces strong immune response and provided an effective protection against iridovirus diseases.

The microbial carbon pump and climate change.

The ocean has been a regulator of climate change throughout the history of Earth. One key mechanism is the mediation of the carbon reservoir by refractory dissolved organic carbon (RDOC), which can either be stored in the water column for centuries or released back into the atmosphere as CO2 depending on the conditions. The RDOC is produced through a myriad of microbial metabolic and ecological processes known as the microbial carbon pump (MCP). Here, we review recent research advances in processes related to the MCP, including the distribution patterns and molecular composition of RDOC, links between the complexity of RDOC compounds and microbial diversity, MCP-driven carbon cycles across time and space, and responses of the MCP to a changing climate. We identify knowledge gaps and future research directions in the role of the MCP, particularly as a key component in integrated approaches combining the mechanisms of the biological and abiotic carbon pumps for ocean negative carbon emissions.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Scinderin promotes glioma cell migration and invasion via remodeling actin cytoskeleton.

BACKGROUND: Glioma is one of the most common intracranial tumors, characterized by invasive growth and poor prognosis. Actin cytoskeletal rearrangement is an essential event of tumor cell migration. The actin dynamics-related protein scinderin (SCIN) has been reported to be closely related to tumor cell migration and invasion in several cancers. AIM: To investigate the role and mechanism of SCIN in glioma. METHODS: The expression and clinical significance of SCIN in glioma were analyzed based on public databases. SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting. Gene silencing was performed using short hairpin RNA transfection. Cell viability, migration, and invasion were assessed using cell counting kit 8 assay, wound healing, and Matrigel invasion assays, respectively. F-actin cytoskeleton organization was assessed using F-actin staining. RESULTS: SCIN expression was significantly elevated in glioma, and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase. Furthermore, SCIN-deficient cells exhibited decreased proliferation, migration, and invasion in U87 and U251 cells. Moreover, knockdown of SCIN inhibited the RhoA/focal adhesion kinase (FAK) signaling to promote F-actin depolymerization in U87 and U251 cells. CONCLUSION: SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling, thereby promoting the migration and invasion of glioma cells. This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.

Rationally Designed Self-Assembling Nanovaccines Elicit Robust Mucosal and Systemic Immunity against Rhabdovirus.

Viral diseases have constantly caused great threats to global public health, resulting in an urgent need for effective vaccines. However, the current viral vaccines often show low immunogenicity. To counter this, we report a smart strategy of a well-designed modular nanoparticle (LSG-TDH) that recapitulates the dominant antigen SG, low-molecular-weight protamine, and tetralysine-modified H-chain apoferritin (TDH). The constructed LSG-TDH nanovaccine could self-assemble into a nanocage structure, which confers excellent mucus-penetrating, cellular affinity, and uptake ability. Studies demonstrate that the LSG-TDH nanovaccine could strongly activate both mucosal and systemic immune responses. Importantly, by immunizing wild-type and TLR2 knockout (TLR2-KO) zebrafish, we found that TLR2 could mediate LSG-TDH-induced adaptive mucosal and systemic immune responses by activating antigen-presenting cells. Collectively, our findings offer new insights into rational viral vaccine design and provide additional evidence of the vital role of TLR2 in regulating adaptive immunity.

Impacts of aging on circadian rhythm and related sleep disorders.

Circadian rhythm is an essential component of biology that organizes the internal synchrony of the organism in response to the environment. Aging significantly impacts circadian rhythm and is also associated with specific sleep complaints in mammals, including earlier awakening and decreased sleep consolidation at the end of the night. However, the regulation mechanism of aging on the circadian rhythm is far from clear. To further understand the impact of aging, we use an existing mathematical model of circadian rhythm combined with the aging system to explore the effects of aging on circadian rhythm and two kinds of sleep disorders, familial late sleep syndrome (FASPS) and delayed sleep syndrome (DSPS). We get a few intriguing findings from numerical simulations. Aging weakens rhythmicity by reducing the amplitude of circadian rhythm. Aging exacerbates the sleep pattern of being early to bed and early to rise by shortening the period of circadian rhythm and advancing the entrainment phase. Aging reduces the ability of the circadian rhythm to respond to light. The elderly need stronger light to get entrainment with the environmental light cycle. It is more difficult for the elderly to recover from disturbed light. Especially elderly people take a longer time to overcome jet lag. Aging worsens the "morningness" of FASPS disorder patients and improves the symptoms of DSPS disorder patients. This study helps to better understand the impacts of aging on circadian rhythm and sleep disorders and provides theoretical support for the treatment of circadian disorders in the elderly.

Improving the Robustness of Time Difference of Arrival Estimation Based on the Energy Center of Gravity Rearrangement.

An accurate estimation of the time difference of arrival (TDOA) is crucial in localization, communication, and navigation. However, a low signal-to-noise ratio (SNR) can decrease the reliability of the TDOA estimation result. Therefore, this study aims to improve the performance of the TDOA estimation of dual-channel sensors for single-sound sources in low-SNR environments. This study introduces the theory of time rearrangement synchrosqueezing transform (TRST) into the time difference of arrival estimation. While the background noise TF points show random time delays, the signal time-frequency (TF) points originating from uniform directions that exhibit identical lags are considered in this study. In addition, the time difference rearrangement synchrosqueezing transform (TDST) algorithm is developed to separate the signal from the background noise by exploiting its distinct time delay characteristics. The implementation process of the proposed algorithm includes four main steps. First, a rough estimation of the time delay is performed by calculating the partial derivative of the short-time cross-power spectrum. Second, a rearrangement operation is conducted to separate the TF points of the signal and noise. Third, the TF points on both sides of the time-delay energy ridge are extracted. Finally, a refined TDOA estimation is realized by applying the inverse Fourier transformation on the extracted TF points. Furthermore, a second-order-based time difference reassigned synchrosqueezing transform algorithm is proposed to improve the robustness of the TDOA estimation by enhancing the TF energy aggregation. The proposed algorithms are verified by simulations and experiments. The results show that the proposed algorithms are more robust and accurate than the existing algorithms.