Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. METHODS: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. RESULTS: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. CONCLUSIONS: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. HIGHLIGHT: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.

Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.

Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.

The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.

Cai's herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus ß cells through the AMPK/mTOR pathway and alleviates inflammatory response.

BACKGROUND: This study investigates the therapeutic mechanisms of Cai's Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice, focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. METHODS: The composition of Cai's Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai's Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement. RESULTS: Cai's Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice, particularly at higher doses. In Min6 cells, Cai's Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/mTOR and P62 expressions in pancreatic islet ß-cells. Furthermore, these effects were converted by si-AMPK interference. CONCLUSION: Cai's Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet ß-cells. These findings highlight its potential as a therapeutic approach for T1DM management.

Rapid identification of bloodstream infection pathogens and drug resistance using Raman spectroscopy enhanced by convolutional neural networks.

Bloodstream infections (BSIs) are a critical medical concern, characterized by elevated morbidity, mortality, extended hospital stays, substantial healthcare costs, and diagnostic challenges. The clinical outcomes for patients with BSI can be markedly improved through the prompt identification of the causative pathogens and their susceptibility to antibiotics and antimicrobial agents. Traditional BSI diagnosis via blood culture is often hindered by its lengthy incubation period and its limitations in detecting pathogenic bacteria and their resistance profiles. Surface-enhanced Raman scattering (SERS) has recently gained prominence as a rapid and effective technique for identifying pathogenic bacteria and assessing drug resistance. This method offers molecular fingerprinting with benefits such as rapidity, sensitivity, and non-destructiveness. The objective of this study was to integrate deep learning (DL) with SERS for the rapid identification of common pathogens and their resistance to drugs in BSIs. To assess the feasibility of combining DL with SERS for direct detection, erythrocyte lysis and differential centrifugation were employed to isolate bacteria from blood samples with positive blood cultures. A total of 12,046 and 11,968 SERS spectra were collected from the two methods using Raman spectroscopy and subsequently analyzed using DL algorithms. The findings reveal that convolutional neural networks (CNNs) exhibit considerable potential in identifying prevalent pathogens and their drug-resistant strains. The differential centrifugation technique outperformed erythrocyte lysis in bacterial isolation from blood, achieving a detection accuracy of 98.68% for pathogenic bacteria and an impressive 99.85% accuracy in identifying carbapenem-resistant Klebsiella pneumoniae. In summary, this research successfully developed an innovative approach by combining DL with SERS for the swift identification of pathogenic bacteria and their drug resistance in BSIs. This novel method holds the promise of significantly improving patient prognoses and optimizing healthcare efficiency. Its potential impact could be profound, potentially transforming the diagnostic and therapeutic landscape of BSIs.

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD+, as well as active DSR2-tube and DSR2-tube-NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: circAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSIONS: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Anthropogenic nitrogen pollution inferred by stable isotope records of crustose coralline algae.

Since reef ecosystems can offer intricate habitats for various marine organisms, calcified reefs may contain valuable long-term environmental data. This study investigated stable isotopic composition of marine organisms from the Taoyuan and Linshanbi crustose coralline algae (CCA) reef ecosystems to understand sewage pollution. CCA samples from Taoyuan (Palaeo Xin A: ∼1000 years old and Palaeo G: ∼7000 years old) and Linshanbi (Palaeo L: ∼7000 years old and modern CCA) had significantly lower δ15N values (2.5-5.6 ‰) compared to modern CCA from Taoyuan (10.2 ± 1.2 ‰). Intertidal organisms from the Taoyuan CCA reef also showed higher δ15N values than those from Linshanbi CCA reef, indicating anthropogenic stress in both ecosystems. Long-term pollution monitoring and effective strategies to mitigate sewage pollution are recommended for these CCA reef ecosystems.

Neurodevelopmental defects in human cortical organoids with N-acetylneuraminic acid synthase mutation.

Biallelic genetic variants in N-acetylneuraminic acid synthase (NANS), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that NANS mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical organoids and notably reduced the proliferation and expansion of neural progenitors. NANS mutation dysregulated neural migration and differentiation, disturbed synapse formation, and weakened neuronal activity. Single-cell RNA sequencing revealed that NANS loss of function markedly altered transcriptional programs involved in neuronal differentiation and ribosomal biogenesis in various neuronal cell types. Similarly, Nans heterozygous mice exhibited impaired cortical neurogenesis and neurobehavioral deficits. Collectively, our findings reveal a crucial role of NANS-mediated endogenous sialic acid biosynthesis in regulating multiple features of human cortical development, thus linking NANS mutation with its clinically relevant neurodevelopmental disorders.

Multi-biological functions of intermedin in diseases.

Intermedin (IMD) is a member of the calcitonin gene-related peptide (CGRP)/calcitonin (CT) superfamily, and it is expressed extensively throughout the body. The typical receptors for IMD are complexes composed of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP), which leads to a biased activation towards Gαs. As a diagnostic and prognostic biomarker, IMD regulates the initiation and metastasis of multiple tumors. Additionally, IMD functions as a proangiogenic factor that can restrain excessive vascular budding and facilitate the expansion of blood vessel lumen, ultimately resulting in the fusion of blood vessels. IMD has protective roles in various diseases, including ischemia-reperfusion injury, metabolic disease, cardiovascular diseases and inflammatory diseases. This review systematically elucidates IMD's expression, structure, related receptors and signal pathway, as well as its comprehensive functions in the context of acute kidney injury, obesity, diabetes, heart failure and sepsis. However, the precise formation process of IMD short peptides in vivo and their downstream signaling pathway have not been fully elucidated yet. Further in-depth studies are need to translate IMD research into clinical applications.

Safety and efficacy of Pimecrolimus in atopic dermatitis among Chinese infants: a sub-group analysis of a five-year open-label study.

INTRODUCTION: Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants. MATERIALS AND METHODS: Patients with AD (≥3 months-<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy. RESULTS: 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1). CONCLUSION: PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

Multiplexed detection of biomarkers using a microfluidic chip integrated with mass-producible micropillar array electrodes.

Quantifying multiple biomarkers with high sensitivity in tiny biological samples is essential to meet the growing demand for point-of-care testing. This paper reports the development of a novel microfluidic device integrated with mass-producible micropillar array electrodes (µAEs) for multiple biomarker detections. The µAE are mass-fabricated by soft lithography and hot embossing technique. Pt-Pd bimetallic nanoclusters (BNC) are modified on the surface of µAEs by constant potential (CP)/multi-potential step (MPS) electrodeposition strategies to improve the electroanalytical performance. The experimental result displays that Pt-Pd BNC/µAEs have good sensitivity enhancement compared with bare planar electrodes and bare µAEs, the enhancement being 56.5 and 9.5 times respectively, from the results of the H2O2 detection. Furthermore, glucose, uric acid and sarcosine were used as model biomarkers to show the biosensing capability with high sensitivity. The linear range and LOD of the glucose, uric acid and sarcosine detection are 0.1 mM-12 mM, 10 µM-800 µM and 2.5 µM-100 µM, 58.5, 3.4 and 0.4 µM, respectively. In particular, biosensing chips show wide linear ranges covering required detection ranges of glucose, uric acid and sarcosine in human serum, indicating the developed device has great potential in self-health management and clinical requirements.

Experimental study on remediation of petroleum-contaminated soil by combination of freeze-thaw and electro-osmosis.

Electro-osmosis has been well recognized as a technique for the remediation of petroleum-contaminated soil, however seasonally freezing and thawing adds the complexity of petroleum mobility in cold regions. To investigate the influence of freeze-thaw on the electroosmotic removal of petroleum and explore the enhancement of freeze-thaw on the electroosmotic remediation efficiency in remediating the petroleum-contaminated soils, a set of laboratory tests were performed in three types of treatment modes, freeze-thaw (FT), electro-osmosis (EO) and freeze-thaw combined electro-osmosis (FE). The petroleum redistributions as well as the moisture content changes after the treatments were evaluated and compared. The petroleum removal rates of the three treatments were analyzed, and the underlying mechanisms were elaborated. The results indicated that the overall efficiency of the treatment mode regarding petroleum removal from soil followed the order of FE > EO > FT, corresponding to 54%, 36% and 21% in maximum, respectively. A considerable amount of water solution with surfactant was driven into contaminated soil during FT process, but the petroleum mobilization primarily occurred inside of the specimen. A higher remediation efficiency was yield in EO mode, but the induced dehydration and cracks leaded to the dramatical depression in the efficiency in further process. It is proposed that the petroleum removal is closely related to the flow of water solution with surfactant that is favorable to the solubility and mobilization of the petroleum in soil. Thus, the water migration induced by freeze-thaw cycles substantially improved the efficiency of the electroosmotic remediation in FE mode that gave the best performance for the remediation of the petroleum-contaminated soil.

Coprecipitation-based synchronous chlorantraniliprole encapsulation with chitosan: carrier-pesticide interactions and release behavior.

BACKGROUND: Controlled-release pesticide formulations have emerged as a promising approach towards sustainable pest control. Herein, an environment-friendly formulation of insecticide chlorantraniliprole (CAP) was fabricated through a simple approach of coprecipitation-based synchronous encapsulation by chitosan (CTS), with carrier-pesticide interaction mechanism and release behavior investigated. RESULTS: The resulting CAP/CTS controlled-release formulation (CCF) showed a good loading content of 28.1% and a high encapsulation efficiency of 75.6%. Instrument determination in combination with molecular dynamics (MD) simulations displayed that the primary interactions between CAP and CTS were physical adsorption and complicated hydrogen (H)-bonds, which formed dominantly between NH in amides [or nitrogen (N) in ring structures] of CAP and hydroxyl (or amino) groups of CTS, as well as oxygen (O) in CAP with hydrogen in CTS or H2 O molecules. The in vitro release tests exhibited obvious pH/temperature sensitivity, with release dynamics following the first-order or Ritger-Peppas model. As the temperature increased, the CAP release process of the Ritger-Peppas model changed from Case-II to anomalous transport, and ultimately to a Fickian diffusion mechanism. The control effect against Plutella xylostella larvae also was evaluated by toxicity tests, where comparable efficacy of CCF to the commercial suspension concentrate was obtained. CONCLUSION: The innovative, easy-to-prepare CCF can be used as a formulation with obvious pH/temperature sensitivity and good efficacy on target pests. This work contributes to the development of efficient and safe pesticide delivery systems, especially using the natural polymer materials as carriers. © 2023 Society of Chemical Industry.

Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons.

The expression of linear DNA sequence is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neurons is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops, and were further validated for changed expression. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

Cardiolipin and OPA1 Team up for Methamphetamine-Induced Locomotor Activity by Promoting Neuronal Mitochondrial Fusion in the Nucleus Accumbens of Mice.

Mitochondria are highly dynamic organelles with coordinated cycles of fission and fusion occurring continuously to satisfy the energy demands in the complex architecture of neurons. How mitochondria contribute to addicted drug-induced adaptable mitochondrial networks and neuroplasticity remains largely unknown. Through liquid chromatography-mass spectrometry-based lipidomics, we first analyzed the alteration of the mitochondrial lipidome of three mouse brain areas in methamphetamine (METH)-induced locomotor activity and conditioned place preference. The results showed that METH remodeled the mitochondrial lipidome of the hippocampus, nucleus accumbens (NAc), and striatum in both models. Notably, mitochondrial hallmark lipid cardiolipin (CL) was specifically increased in the NAc in METH-induced hyperlocomotor activity, which was accompanied by an elongated giant mitochondrial morphology. Moreover, METH significantly boosted mitochondrial respiration and ATP generation as well as the copy number of mitochondrial genome DNA in the NAc. By screening the expressions of mitochondrial dynamin-related proteins, we found that repeated METH significantly upregulated the expression of long-form optic atrophy type 1 (L-OPA1) and enhanced the interaction of L-OPA1 with CL, which may promote mitochondrial fusion in the NAc. On the contrary, neuronal OPA1 depletion in the NAc not only recovered the dysregulated mitochondrial morphology and synaptic vesicle distribution induced by METH but also attenuated the psychomotor effect of METH. Collectively, upregulated CL and OPA1 cooperate to mediate METH-induced adaptation of neuronal mitochondrial dynamics in the NAc, which correlates with the psychomotor effect of METH. These findings propose a potential therapeutic approach for METH addiction by inhibiting neuronal mitochondrial fusion.

Correlation evaluation between cancer microenvironment related genes and prognosis based on intelligent medical internet of things.

The study of tumor microenvironment plays an important role in the treatment of cancer patients. In this paper, intelligent medical Internet of Things technology was used to analyze cancer tumor microenvironment-related genes. Through experiments designed and analyzed cancer-related genes, this study concluded that in cervical cancer, patients with high expression of P16 gene had a shorter life cycle and a survival rate of 35%. In addition, through investigation and interview, it was found that patients with positive expression of P16 and Twist genes had a higher recurrence rate than patients with negative expression of both genes; high expression of FDFT1, AKR1C1, and ALOX12 in colon cancer is associated with short survival; high expressions of HMGCR and CARS1 is associated with longer survival; overexpression of NDUFA12, FD6, VEZT, GDF3, PDE5A, GALNTL6, OPMR1, and AOAH in thyroid cancer is associated with shortened survival; high expressions of NR2C1, FN1, IPCEF1, and ELMO1 is associated with prolonged survival. Among the genes associated with the prognosis of liver cancer, the genes associated with shorter survival period are AGO2, DCPS, IFIT5, LARP1, NCBP2, NUDT10, and NUDT16; the genes associated with longevity are EIF4E3, EIF4G3, METTL1, NCBP1, NSUN2, NUDT11, NUDT4, and WDR4. Depending on the prognostic role of genes in different cancers, they can influence patients to achieve the effect of reducing patients' symptoms. In the process of disease analysis of cancer patients, this paper uses bioinformation technology and Internet of things technology to promote the development of medical intelligence.

Neonatal exposure to sevoflurane induces adolescent neurobehavioral dysfunction by interfering with hippocampal glycerophoslipid metabolism in rats.

Sevoflurane exposure in the neonatal period causes long-term developmental neuropsychological dysfunction, including memory impairment and anxiety-like behaviors. However, the molecular mechanisms underlying such effects have not been fully elucidated. In this study, we investigated the effect of neonatal exposure to sevoflurane on neurobehavioral profiles in adolescent rats, and applied an integrated approach of lipidomics and proteomics to investigate the molecular network implicated in neurobehavioral dysfunction. We found that neonatal exposure to sevoflurane caused cognitive impairment and social behavior deficits in adolescent rats. Lipidomics analyses revealed that sevoflurane significantly remodeled hippocampal lipid metabolism, including lysophatidylcholine (LPC) metabolism, phospholipid carbon chain length and carbon chain saturation. Through a combined proteomics analysis, we found that neonatal exposure to sevoflurane significantly downregulated the expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1), a key enzyme in the regulation of phospholipid metabolism, in the hippocampus of adolescent rats. Importantly, hippocampal LPCAT1 overexpression restored the dysregulated glycerophospholipid (GP) metabolism and alleviated the learning and memory deficits caused by sevoflurane. Collectively, our evidence that neonatal exposure to sevoflurane downregulates LPCAT1 expression and dysregulates GP metabolism in the hippocampus, which may contribute to the neurobehavioral dysfunction in the adolescent rats.