Microglia lactylation in relation to central nervous system diseases.

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Clinical Characteristics and Patterns of Immune Responses in COVID-19 Patients From a Rural Community Hospital.

Background Although demographic and clinical factors such as age, certain comorbidities, and sex have been associated with COVID-19 outcomes, these studies were largely conducted in urban populations affiliated with large academic medical centers. There have been very few studies focusing on rural populations that also characterize broader changes in inflammatory cytokines and chemokines. Methodology A single-center study was conducted between June 2020 and March 2021 in Abilene, Texas, USA. Patients were included if they presented to the hospital for treatment of COVID-19, had extra biological materials from routine care available, and were between the ages of 0 to 110 years. There were no exclusion criteria. Patient characteristics, symptom presentation, and clinical laboratory results were extracted from electronic health records. Blood specimens were analyzed by protein microarray to quantitate 40 immunological biomarkers. Results A total of 122 patients were enrolled, of whom 81 (66%) were admitted to the general non-critical inpatient unit, 37 (30%) were admitted to the intensive or critical care units, and four (3.2%) were treated outpatient. Most hospitalized COVID-19 patients in this rural population were elderly, male, obese, and retired individuals. Predominant symptoms for non-critical patients were shortness of breath, fever, and fatigue. Ferritin levels for outpatient patients were lower on average than those in an inpatient setting and lactate dehydrogenase (LDH) levels were noted to be lower in non-critical and outpatient than those in the intensive care unit setting. Inflammatory biomarkers were positively correlated and consistent with inflammatory cascade. Interleukin (IL)-10 was positively correlated while platelet-derived growth factor was negatively correlated with inflammatory biomarkers. Patients ≥65 years had significantly higher levels of LDH and seven cytokines/chemokines (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin IL-1b, IL-6, IL-10, IL-11, macrophage inflammatory protein (MIP)-1d, and IL-8) while levels of five other immune molecules (intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), tissue inhibitor of metalloproteinase 2 (TIMP-2), IL-2, and IL-4) were significantly lower compared to those <65 years. Females had significantly higher levels of LDH and 10 cytokines/chemokines (GM-CSF, IL-1b, IL-6, IL-10, IL-11, IL-15, IL-16, MIP-1a, MIP-1d, and IL-8) while levels of TIMP-2 and IL-4 were significantly lower than male patients. Conclusions The clinical characteristics of this rural cohort of hospitalized patients differed somewhat from nationally reported data. The contributions of social, environmental, and healthcare access factors should be investigated. We identified age and sex-associated differences in immunological response markers that warrant further investigation to identify the underlying molecular mechanisms and impact on COVID-19 pathogenesis.

Effect of psyllium husk powder on the gelation behavior, microstructure, and intermolecular interactions in myofibrillar protein gels from Andrias davidianus.

The interaction between proteins and soluble dietary fibers plays a vital role in the development of animal-derived foods. Herein, the effects of different contents (0-3.0%) of round-bracted psyllium husk powder (PHP) on the gelation behavior, microstructure, and intermolecular interactions of Andrias davidianus myofibrillar protein (MP) were investigated. Rheological and chemical forces suggested that PHP (1.5%-2.0%) enhanced the functional properties of MP at low ionic strength, thereby increasing the viscoelasticity of mixed gels. SDS-PAGE revealed that PHP reinforced the cross-linking and aggregation of protein molecules. Circular dichroism spectroscopy, low-field nuclear magnetic resonance, and scanning electron microscopy demonstrated that PHP induced the transformation of α-helix (decreased by 14.85%) to an ordered ß-sheet structure (increased by 81.58%), which was more favorable for the formation of dense network structure and improved (10.53%) the water retention of MP gels. This study provided new insights for PHP to effectively meliorate the heat-induced gelling properties of MP.

Highly Stretchable and Oriented Wafer-Scale Semiconductor Films for Organic Phototransistor Arrays.

Stretchable organic phototransistor arrays have potential applications in artificial visual systems due to their capacity to perceive ultraweak light across a broad spectrum. Ensuring uniform mechanical and electrical performance of individual devices within these arrays requires semiconductor films with large-area scale, well-defined orientation, and stretchability. However, the progress of stretchable phototransistors is primarily impeded by their limited electrical properties and photodetection capabilities. Herein, wafer-scale and well-oriented semiconductor films were successfully prepared using a solution shearing process. The electrical properties and photodetection capabilities were optimized by improving the polymer chain alignment. Furthermore, a stretchable 10 × 10 transistor array with high device uniformity was fabricated, demonstrating excellent mechanical robustness and photosensitive imaging ability. These arrays based on highly stretchable and well-oriented wafer-scale semiconductor films have great application potential in the field of electronic eye and artificial visual systems.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.

INTRODUCTION: Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI. METHODS: Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results. RESULTS: EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. CONCLUSION: EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment.

Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM. Our observations suggest that HSCs can respond to the mechanical heterogeneity of the BM microenvironment, exhibiting diversity in cell mechanics, haematopoietic pool maintenance and differentiated lineages. Hydrogels with higher stiffness promote the preservation of long-term repopulating HSCs (LT-HSCs), while those with lower stiffness support multi-potent progenitors (MPPs) viability in vitro. Furthermore, we established a comprehensive transcriptional profile of haematopoietic subpopulations to reflect the multipotency of haematopoietic stem and progenitor cells (HSPCs) that are modulated by niche-like stiffness. Our findings demonstrate that HSPCs exhibit completely distinct downstream differentiated preferences within hydrogel systems of varying stiffness. This highlights the crucial role of tissue-specific mechanical properties in HSC lineage decisions, which may provide innovative solutions to clinical challenges.

Increased crossing of thermal stress thresholds of vegetation under global warming.

Temperature extremes exert a significant influence on terrestrial ecosystems, but the precise levels at which these extremes trigger adverse shifts in vegetation productivity have remained elusive. In this study, we have derived two critical thresholds, using standard deviations (SDs) of growing-season temperature and satellite-based vegetation productivity as key indicators. Our findings reveal that, on average, vegetation productivity experiences rapid suppression when confronted with temperature anomalies exceeding 1.45 SD above the mean temperature during 2001-2018. Furthermore, at temperatures exceeding 2.98 SD above the mean, we observe the maximum level of suppression, particularly in response to the most extreme high-temperature events. When Earth System Models are driven by a future medium emission scenario, they project that mean temperatures will routinely surpass both of these critical thresholds by approximately the years 2050 and 2070, respectively. However, it is important to note that the timing of these threshold crossings exhibits spatial variation and will appear much earlier in tropical regions. Our finding highlights that restricting global warming to just 1.5°C can increase safe areas for vegetation growth by 13% compared to allowing warming to reach 2°C above preindustrial levels. This mitigation strategy helps avoid exposure to detrimental extreme temperatures that breach these thresholds. Our study underscores the pivotal role of climate mitigation policies in fostering the sustainable development of terrestrial ecosystems in a warming world.

CircGNAO1 strengthens its host gene GNAO1 expression for suppression of hepatocarcinogenesis.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent primary liver carcinoma. Guanine nucleotide-binding protein, α-activating activity polypeptide O (GNAO1) was reported to be under-expressed in HCC tissues. This study aimed to investigate the GNAO1-derived circular RNA (circRNA) and its molecular mechanisms in HCC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were applied to examine RNA and protein levels. Functional experiments were performed to study HCC cell proliferation, cell cycle and cellular senescence. The interactions among circGNAO1, GNAO1 and DNA methyltransferase 1 (DNMT1) were examined by mechanism assays. The methylation level was analyzed by bisulfite sequencing PCR (BSP). Results: CircGNAO1 is down-regulated and positively associated with GNAO1 in HCC tissues. Overexpression of circGNAO1 inhibits cell proliferation, induces cell cycle arrest and facilitates cell senescence in HCC cells. CircGNAO1 facilitates the progression of HCC via modulating GNAO1. Mechanistically, circGNAO1 enhances the transcription of GNAO1 by sequestering DNMT1, thereby up-regulating GNAO1 expression in HCC cells. Conclusions: CircGNAO1 up-regulates its host gene GNAO1 expression for suppression of hepatocarcinogenesis.

Nitrite induces hepatic glucose and lipid metabolism disorders in zebrafish through mitochondrial dysfunction and ERs response.

Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.

Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Exploring the effects of combining health qigong and dance on working memory in middle-aged and elderly women: A preliminary investigation.

OBJECTIVE: Cognitive decline represents a critical clinical and public health issue that adversely affects the quality of life for older patients and their families. This concern was exacerbated by the reduced engagement in outdoor activities among seniors during the COVID-19 pandemic, presenting substantial challenges to aging societies. The objective of this study was to investigate the impact of health qigong combined with Tibetan dance on working memory in middle-aged and elderly women, and to determine its potential as a preventive strategy against cognitive disorders. METHODS: A pilot study was conducted to compare the effects of a Health Qigong exercise intervention with those of everyday life and sports routines. The primary outcome measure was working memory assessed using a 2-Back working memory task research paradigm. Between July and September 2021, a total of 33 women were divided into four groups: two middle-aged groups (N = 18, with 8 women in the experimental group and 10 in the control group) and two elderly groups (N = 15, with 7 in the experimental group and 8 in the control group). Participants in the experimental groups underwent a 10-week intervention, consisting of three 60-min sessions per week. Each session included a warm-up, Health Qigong combined with Tibetan dance, and a cool-down. Throughout the study, all participants continued their daily routines. Response times and error rates were analyzed using a mixed-design repeated-measures analysis of variance. RESULTS: A simple effects analysis revealed that Health Qigong combined with Tibetan dance significantly enhanced 2-Back response time and error rate in the middle-aged group. In contrast, the 2-Back error rate significantly increased in the elderly control group that did not receive the intervention (p < 0.05). CONCLUSION: Health Qigong demonstrates beneficial effects on middle-aged and elderly women. Combining Health Qigong with dance may serve as a preventive measure against cognitive disorders. This pioneering study conducted during the COVID-19 pandemic, assesses the new possibility of Health Qigong and dance, with the objective to offer more diverse indoor exercise options for middle-aged and elderly women.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Bimetallic PtAu-Decorated SnO2 Nanospheres Exhibiting Enhanced Gas Sensitivity for Ppb-Level Acetone Detection.

Acetone is a biomarker found in the expired air of patients suffering from diabetes. Therefore, early and accurate detection of its concentration in the breath of such patients is extremely important. We prepared Tin(IV) oxide (SnO2) nanospheres via hydrothermal treatment and then decorated them with bimetallic PtAu nanoparticles (NPs) employing the approach of in situ reduction. The topology, elemental composition, as well as crystal structure of the prepared materials were studied via field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The findings revealed that bimetallic PtAu-decorated SnO2 nanospheres (PtAu/SnO2) were effectively synthesized as well as PtAu NPs evenly deposited onto the surface of the SnO2 nanospheres. Pure SnO2 nanospheres and PtAu/SnO2 sensors were prepared, and their acetone gas sensitivity was explored. The findings demonstrated that in comparison to pristine SnO2 nanosphere sensors, the sensors based on PtAu/SnO2 displayed superior sensitivity to acetone of 0.166-100 ppm at 300 °C, providing a low theoretical limit of detection equal to 158 ppm. Moreover, the PtAu/SnO2 sensors showed excellent gas response (Ra/Rg = 492.3 to 100 ppm), along with fast response and recovery (14 s/13 s to 10 ppm), good linearity of correlation, excellent repeatability, long-term stability, and satisfactory selectivity at 300 °C. This improved gas sensitivity was because of the electron sensitization of the Pt NPs, the chemical sensitization of the Au NPs, as well as the synergistic effects of bimetallic PtAu. The PtAu/SnO2 sensors have considerable potential for the early diagnosis and screening of diabetes.

Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAcCRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAcCRH neurons during wakefulness and rewarding stimulation. Activation of NAcCRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAcCRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAcCRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAcCRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.

Dominant role of the non-forest woody vegetation in the post 2015/16 El Niño tropical carbon recovery.

The extreme dry and hot 2015/16 El Niño episode caused large losses in tropical live aboveground carbon (AGC) stocks. Followed by climatic conditions conducive to high vegetation productivity since 2016, tropical AGC are expected to recover from large losses during the El Niño episode; however, the recovery rate and its spatial distribution remain unknown. Here, we used low-frequency microwave satellite data to track AGC changes, and showed that tropical AGC stocks returned to pre-El Niño levels by the end of 2020, resulting in an AGC sink of 0.18 0.14 0.26 $$ {0.18}_{0.14}^{0.26} $$ Pg C year-1 during 2014-2020. This sink was dominated by strong AGC increases ( 0.61 0.49 0.84 $$ {0.61}_{0.49}^{0.84} $$ Pg C year-1) in non-forest woody vegetation during 2016-2020, compensating the forest AGC losses attributed to the El Niño event, forest loss, and degradation. Our findings highlight that non-forest woody vegetation is an increasingly important contributor to interannual to decadal variability in the global carbon cycle.

Circulating tumor DNA assisting lymphoma genetic feature profiling and identification.

INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.

Branch Chain Amino Acid Metabolism Promotes Brain Metastasis of NSCLC through EMT Occurrence by Regulating ALKBH5 activity.

Metabolic reprogramming is one of the essential features of tumors that may dramatically contribute to cancer metastasis. Employing liquid chromatography-tandem mass spectrometry-based metabolomics, we analyzed the metabolic profile from 12 pairwise serum samples of NSCLC brain metastasis patients before and after CyberKnife Stereotactic Radiotherapy. We evaluated the histopathological architecture of 144 surgically resected NSCLC brain metastases. Differential metabolites were screened and conducted for functional clustering and annotation. Metabolomic profiling identified a pathway that was enriched in the metabolism of branched-chain amino acids (BCAAs). Pathologically, adenocarcinoma with a solid growth pattern has a higher propensity for brain metastasis. Patients with high BCAT1 protein levels in lung adenocarcinoma tissues were associated with a poor prognosis. We found that brain NSCLC cells had elevated catabolism of BCAAs, which led to a depletion of α-KG. This depletion, in turn, reduced the expression and activity of the m6A demethylase ALKBH5. Thus, ALKBH5 inhibition participated in maintaining the m6A methylation of mesenchymal genes and promoted the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC cells and the proliferation of NSCLC cells in the brain. BCAA catabolism plays an essential role in the metastasis of NSCLC cells.

The Impact of Microwave Annealing on MoS2 Devices Assisted by Neural Network-Based Big Data Analysis.

Microwave annealing, an emerging annealing method known for its efficiency and low thermal budget, has established a foundational research base in the annealing of molybdenum disulfide (MoS2) devices. Typically, to obtain high-quality MoS2 devices, mechanical exfoliation is commonly employed. This method's challenge lies in achieving uniform film thickness, which limits the use of extensive data for studying the effects of microwave annealing on the MoS2 devices. In this experiment, we utilized a neural network approach based on the HSV (hue, saturation, value) color space to assist in distinguishing film thickness for the fabrication of numerous MoS2 devices with enhanced uniformity and consistency. This method allowed us to precisely assess the impact of microwave annealing on device performance. We discovered a relationship between the device's electrical performance and the annealing power. By analyzing the statistical data of these electrical parameters, we identified the optimal annealing power for MoS2 devices as 700 W, providing insights and guidance for the microwave annealing process of two-dimensional materials.