Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

Prevalence and molecular detection of Babesia microti in rodents in Southeastern Shanxi, China.

Babesia is a tick-transmitted parasite that infects wild and domestic animals, causes babesiosis in humans, and is an increasing public health concern. Here, we investigated the prevalence and molecular characteristics of Babesia infections in the rodents in Southeastern Shanxi, China. Small rodents were captured, and the liver and spleen tissues were used for Babesia detection using traditional PCR and sequencing of the partial 18S rRNA gene. The analysis revealed that 27 of 252 small rodents were positive for Babesia, with an infection rate of 10.71%. The infection rates in different sexes and rodent tissues were not statistically different, but those in different rodent species, habitats, and sampling sites were statistically different. The highest risk of Babesia infection was observed in Niviventer confucianus captured from the forests in Huguan County. Forty-three sequences from 27 small rodents positive for Babesia infection were identified as Babesia microti, including 42 sequences from 26 N. confucianus, and one sequence from Apodemus agrarius. Phylogenetic analysis showed that all sequences were clustered together and had the closest genetic relationship with Babesia microti strains isolated from Rattus losea and N. confucianus in China, and belonged to the Kobe-type, which is pathogenic to humans. Compared to other Kobe-type strains based on the nearly complete 18S rRNA gene, the sequences obtained in this study showed the difference by 1-3 bp. Overall, a high prevalence of Babesia microti infection was observed in small rodents in Southeastern Shanxi, China, which could benefit us to take the implementation of relevant prevention and control measures in this area.

Predicting and refining acid modifications of biochar based on machine learning and bibliometric analysis: Specific surface area, average pore size, and total pore volume.

Acid-modified biochar is a modified biochar material with convenient preparation, high specific surface area, and rich pore structure. It has great potential for application in the heavy metal remediation, soil amendments and carrying catalysts. Specific surface area (SSA), average pore size (APS) and total pore volume (TPV) are the key properties that determine its adsorption capacity, reactivity, and water holding capacity, and an intensive study of these properties is essential to optimize the performance of biochar. But the complex interactions among the preparation conditions obstruct finding the optimal modification strategy. This study collected dataset through bibliometric analysis and used four typical machine learning models to predict the SSA, APS, and TPV of acid-modified biochar. The results showed that the extreme gradient boosting (XGB) was optimal for the test results (SSA R2 = 0.92, APS R2 = 0.87, TPV R2 = 0.96). The model interpretation revealed that the modification conditions were the major factors affecting SSA and TPV, and the pyrolysis conditions were the major factors affecting APS. Based on the XGB model, the modification conditions of biochar were optimized, which revealed the ideal preparation conditions for producing the optimal biochar (SSA = 727.02 m2/g, APS = 5.34 nm, TPV = 0.68 cm3/g). Moreover, the biochar produced under specific conditions verified the generalization ability of the XGB model (R2 = 0.99, RMSE = 12.355). This study provides guidance for optimizing the preparation strategy of acid-modified biochar and promotes its potentiality for industrial application.

[Expression and clinical significance of serum squamous cell carcinoma antigen（SCCAg） in sinonasal inverted papilloma].

Objective:To compare the expression levels of SCCAg in inverted papilloma of the nasal sinuses and other sinuses and sinus masses. To investigate the correlation between the expression of SCCAg in sinonasal inverted papilloma and outcome. Methods:Sixty-eight patients with unilateral nasal and sinus masses admitted to the Otorhinolaryngology Center of the Affiliated Hospital of Guangdong Medical University from September 2020 to February 2023 were randomly selected, including 31 patients with inverted papilloma （experimental group） and 37 patients with unilateral nasal and sinus masses excluding inverted papilloma （control group）. The application of automatic chemiluminescence immunoassay to test the serum SCCAg of the experimental group before surgery and 1 week after surgery, and the control group to measure the serum SCCAg before surgery. Clinical data were also collected. Results:There was no significant difference between the experimental group and the control group in gender and preoperative peripheral blood inflammatory indicators. However, there was significant difference in age and preoperative serum SCCAg level（P<0.001）. The serum SCCAg levels of the experimental group before and 1 week after surgery were significantly different（P<0.001）. The positive predictive value, negative predictive value, sensitivity and specificity of serum SCCAg in the diagnosis of varus papilloma were 92.6%, 85.4%, 77.4%, 94.6% and 0.72, respectively. The effect of serum SCCAg in the diagnosis of varus papilloma was analyzed by drawing the subject's working characteristic curve, and the area under the curve was 0.968（P<0.001）. When serum SCCAg greater than 2.7 ng/mL, the sensitivity and specificity were 67.7% and 94.6%, respectively. There was statistical significance in serum SCCAg levels between patients with and without recurrence（P<0.05）. Conclusion:The level of SCCAg in unilateral nasal and sinuses tumors, excluding squamous cell carcinoma, was significantly increased in inverted papilloma. The detection of serum SCCAg can be used as a simple and cost-effective auxiliary diagnostic tool for patients with nasal inverted papilloma before operation. Significant differences in preoperative and postoperative levels can be used for preliminary evaluation of surgical efficacy. Monitoring the serum SCCAg level in patients with inverted papilloma after surgery can predict recurrence and provide a simple and feasible method for postoperative follow-up.

Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space.

Optimization techniques play a pivotal role in advancing drug development, serving as the foundation of numerous generative methods tailored to efficiently design optimized molecules derived from existing lead compounds. However, existing methods often encounter difficulties in generating diverse, novel, and high-property molecules that simultaneously optimize multiple drug properties. To overcome this bottleneck, we propose a multiobjective molecule optimization framework (MOMO). MOMO employs a specially designed Pareto-based multiproperty evaluation strategy at the molecular sequence level to guide the evolutionary search in an implicit chemical space. A comparative analysis of MOMO with five state-of-the-art methods across two benchmark multiproperty molecule optimization tasks reveals that MOMO markedly outperforms them in terms of diversity, novelty, and optimized properties. The practical applicability of MOMO in drug discovery has also been validated on four challenging tasks in the real-world discovery problem. These results suggest that MOMO can provide a useful tool to facilitate molecule optimization problems with multiple properties.

Quantitative assessment of brain injury and concussion induced by an unintentional soccer ball impact.

BACKGROUND: Accidental impact on a player's head by a powerful soccer ball may lead to brain injuries and concussions during games. It is crucial to assess these injuries promptly and accurately on the field. However, it is challenging for referees, coaches, and even players themselves to accurately recognize potential injuries and concussions following such impacts. Therefore, it is necessary to establish a list of minimum ball velocity thresholds that can result in concussions at different impact locations on the head. Additionally, it is important to identify the affected brain regions responsible for impairments in brain function and potential clinical symptoms. METHODS: By using a full human finite element model, dynamic responses and brain injuries caused by unintentional soccer ball impacts on six distinct head locations (forehead, tempus, crown, occiput, face, and jaw) at varying ball velocities (10, 15, 20, 25, 30, 35, 40, and 60 m/s) were simulated and investigated. Intracranial pressure, Von-Mises stress, and first principal strain were analyzed, the ball velocity thresholds resulting in concussions at different impact locations were evaluated, and the damage evolution patterns in the brain tissue were analyzed. RESULTS: The impact on the occiput is most susceptible to induce brain injuries compared to all other impact locations. For a conservative assessment, the risk of concussion is present once the soccer ball reaches 17.2 m/s in a frontal impact, 16.6 m/s in a parietal impact, 14.0 m/s in an occipital impact, 17.8 m/s in a temporal impact, 18.5 m/s in a facial impact or 19.2 m/s in a mandibular impact. The brain exhibits the most significant dynamic responses during the initial 10-20 ms, and the damaged regions are primarily concentrated in the medial temporal lobe and the corpus callosum, potentially causing impairments in brain functions. CONCLUSIONS: This work offers a framework for quantitatively assessing brain injuries and concussions induced by an unintentional soccer ball impact. Determining the ball velocity thresholds at various impact locations provides a benchmark for evaluating the risks of concussion. The examination of brain tissue damage evolution introduces a novel approach to linking biomechanical responses with possible clinical symptoms.

Facile hydrothermal assembly of three-dimensional GO-MTZE composite and its adsorption properties toward Cu2.

Three-dimensional (3D) graphene oxide (GO)-based aerogels, GO and 4-methyl-5-thiazoleethanol (MTZE) composites, were prepared by a facile hydrothermal method. Due to the hydrogen bonding and π-π stacking interactions, the produced 3D GO-MTZE composites possessed large cylindrical structures. The morphologies, composition, and chemical states of 3D GO-MTZE3:1 composite were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and N2 adsorption-desorption isotherms based on the Brunauer-Emmett-Teller (BET) method. The existence of nitrogen (N)-containing heterocyclic system and oxygen (O)-containing branched chain of MTZE contributed to the formation of 3D structures, while the complexation effect of heterocyclic sulfur (S)- and N-containing functional groups of MTZE for metal cations dominated the adsorption performance of 3D GO-MTZE3:1 composite, which could selectively adsorb copper ions (Cu2+). In addition, the better hydrophobic property of 3D GO-MTZE3:1 composite facilitates its facile recycling from aqueous solution after adsorption. The adsorption data of 3D GO-MTZE3:1 composite toward Cu2+ fitted well (R2 = 0.9996) with the linear pseudo-second-order kinetic model, giving an equilibrium rate constant (k2) of 0.0187 g mg-1 min-1. The linear Langmuir isothermal model could more accurately describe the experimental data, indicating the adsorption process is mainly dominated by the complexation interactions between MTZE and Cu2+. The thermodynamic parameters of ΔG° (< 0), ΔH° (> 0), and ΔS° (> 0) further indicate that the adsorption is a spontaneous and endothermic, confirming that the complexation between Cu2+ and 3D GO-MTZE3:1 composite occurs. Due to its high selectivity for Cu2+, good hydrophobicity, and excellent stability, the developed 3D GO-MTZE3:1 composite possesses might be promisingly used in the aqueous selective enrichment/removal of Cu2+.

LINC00152: Potential driver oncogene in pan-cancer.

Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

Cu2O-catalyzed cascade phosphinylation/cyclization of 2'-aminochalcones for the synthesis of hemi-indigo derivatives.

A Cu2O-catalyzed cascade phosphinylation/cyclization reaction of 2'-aminochalcones and diphenylphosphine oxides to produce hemi-indigo derivatives has been developed. This strategy facilitates the sequential formation of a C-P bonds and a C-N bond in a single reaction step. Notably, the approach features one-pot operation, an earth-abundant copper catalyst, readily available starting materials, a broad substrate scope and high compatibility with functional groups, providing 33 compounds in acceptable yields.

Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer.

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.

DUSP8-attenuated ERK1/2 signaling mediates lipogenesis and steroidogenesis in chicken granulosa cells.

The lipogenesis and steroidogenesis of granulosa cells are crucial during follicular development, yet it remains unclear whether dual-specificity phosphatase 8 (DUSP8) is involved. In this study, the specific role of DUSP8 in lipogenesis and steroidogenesis was investigated through culturing chicken granulosa cells in vitro. The results revealed that the expression levels of adipogenic genes were elevated after DUSP8 overexpression and reduced after knockdown. The same was observed for lipid deposition in granulosa cells. Meanwhile, the steroidogenic gene expression and progesterone synthesis were promoted after DUSP8 overexpression and inhibited after knockdown. In addition, we also found that DUSP8 blocked the phosphorylation of extracellular regulatory kinase 1/2 (ERK1/2). Based on the previous results that activated ERK1/2 signaling inhibited lipid deposition and progesterone synthesis in chicken granulosa cells, we demonstrated that DUSP8 promoted lipid deposition and progesterone synthesis through mediating the ERK1/2 signaling pathway. The results will improve our understanding of the molecular regulatory mechanisms regarding lipid metabolism and progesterone synthesis in chicken granulosa cells.

HANSynergy: Heterogeneous Graph Attention Network for Drug Synergy Prediction.

Drug synergy therapy is a promising strategy for cancer treatment. However, the extensive variety of available drugs and the time-intensive process of determining effective drug combinations through clinical trials pose significant challenges. It requires a reliable method for the rapid and precise selection of drug synergies. In response, various computational strategies have been developed for predicting drug synergies, yet the exploitation of heterogeneous biological network features remains underexplored. In this study, we construct a heterogeneous graph that encompasses diverse biological entities and interactions, utilizing rich data sets from sources, such as DrugCombDB, PubChem, UniProt, and cancer cell line encyclopedia (CCLE). We initialize node feature representations and introduce a novel virtual node to enhance drug representation. Our proposed method, the heterogeneous graph attention network for drug-drug synergy prediction (HANSynergy), has been experimentally validated to demonstrate that the heterogeneous graph attention network can extract key node features, efficiently harness the diversity of information, and further enhance network functionality through the incorporation of a multihead attention mechanism. In the comparative experiment, the highest accuracy (Acc) and area under the curve (AUC) are 0.877 and 0.947, respectively, in DrugCombDB_early data set, demonstrating the superiority of HANSynergy over the competing methods. Moreover, protein-protein interactions are important in understanding the mechanism of action of drugs. The heterogeneous attention mechanism facilitates protein-protein interaction analysis. By analyzing the changes of attention weight before and after heterogeneous network training, we investigated proteins that may be associated with drug combinations. Additionally, case studies align our findings with existing research, underscoring the potential of HANSynergy in drug synergy prediction. This advancement not only contributes to the burgeoning field of drug synergy prediction but also holds the potential to provide valuable insights and uncover new drug synergies for combating cancer.

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp.

OBJECTIVE: 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. METHODS: Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. RESULTS: Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. CONCLUSIONS: When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.

Multiple Unfolded Protein Response pathways cooperate to link cytosolic dsDNA release to Stimulator of Interferon Gene (STING) activation.

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-ß expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-ß induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-ß, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-ß mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-ß via mitochondrial dsDNA release.

Helmet wearing detection algorithm based on improved YOLOv5.

In industrial production, workers need to wear safety helmets at all times. However, due to different lighting, viewing angles, and the tendency of people to block each other, the precision of target detection is not high enough. Aiming at this problem, a real-time detection of helmets was achieved by improving the YOLOv5 algorithm. This algorithm introduces the lightweight network structure FasterNet, which uses partial convolution as the main operator to reduce the amount of calculations and parameters of the network; the boundary regression loss function Wise-IoU loss function with a dynamic focusing mechanism replaces the original loss function in YOLOv5; finally, the CBAM attention mechanism is introduced to obtain global context information and improve the detection ability of small targets. The experimental results show that the parameters of the improved YOLOv5 model are reduced by 12.68%, the computational amount is reduced by 10.8%, the mAP is increased from 88.3 to 92.3%, and the inference time is reduced by 81.5%, which is better than the performance of the original model and can detect helmet wearing effectively and in real time.

Highly Sensitive and Selective Toluene Gas Sensors Based on ZnO Nanoflowers Decorated with Bimetallic AuPt.

Efficient sensors for toluene detecting are urgently needed to meet people's growing demands for both environment and personal health. Metal oxide semiconductor (MOS)-based sensors have become brilliant candidates for the detection of toluene because of their superior performance over gas sensing. However, gas sensors based on pure MOS have certain limitations in selectivity, operating temperature, and long-term stability, which hinders their further practical applications. Noble metals (including Ag, Au, Pt, Pd, etc.) have the ability to enhance the performance of MOS-based sensors via surface functionalization. Herein, ZnO nanoflowers (ZNFs) modified with bimetallic AuPt are prepared for toluene detection through hydrothermal method. The response of a AuPt@ZNF-based gas sensor can reach 69.7 at 175 °C, which is 30 times, 9 times, and 10 times higher than that of the original ZNFs, Au@ZNFs, and Pt@ZNFs, respectively. Furthermore, the sensor also has a lower optimal operating temperature (175 °C), good stability (94% of previous response after one month), and high selectivity towards toluene, which is the result of the combined influence of the electronic and chemical sensitization of noble metals, as well as the unique synergistic effect of the AuPt alloy. In summary, AuPt@ZNF-based sensors can be further applied in toluene detection in practical applications.

Enhanced Acetone Sensing Properties Based on Au-Pd Decorated ZnO Nanorod Gas Sensor.

The mature processes of metal oxide semiconductors (MOS) have attracted considerable interest. However, the low sensitivity of metal oxide semiconductor gas sensors is still challenging, and constrains its practical applications. Bimetallic nanoparticles are of interest owing to their excellent catalytic properties. This excellent feature of bimetallic nanoparticles can solve the problems existing in MOS gas sensors, such as the low response, high operating temperature and slow response time. To enhance acetone sensing performance, we successfully synthesized Au-Pd/ZnO nanorods. In this work, we discovered that Au-Pd nanoparticles modified on ZnO nanorods can remarkably enhance sensor response. The Au-Pd/ZnO gas sensor has long-term stability and an excellent response/recovery process. This excellent sensing performance is attributed to the synergistic catalytic effect of bimetallic AuPd nanoparticles. Moreover, the electronic and chemical sensitization of noble metals also makes a great contribution. This work presents a simple method for preparing Au-Pd/ZnO nanorods and provides a new solution for the detection of acetone based on metal oxide semiconductor.

Identification of a mosaic MTOR variant in purified neuronal DNA in a patient with focal cortical dysplasia using a novel depth electrode harvesting technique.

OBJECTIVE: Recent studies have identified brain somatic variants as a cause of focal epilepsy. These studies relied on resected tissue from epilepsy surgery, which is not available in most patients. The use of trace tissue adherent to depth electrodes used for stereo electroencephalography (EEG) has been proposed as an alternative but is hampered by the low cell quality and contamination by nonbrain cells. Here, we use our improved depth electrode harvesting technique that purifies neuronal nuclei to achieve molecular diagnosis in a patient with focal cortical dysplasia (FCD). METHODS: Depth electrode tips were collected, pooled by brain region and seizure onset zone, and nuclei were isolated and sorted using fluorescence-activated nuclei sorting (FANS). Somatic DNA was amplified from neuronal and astrocyte nuclei using primary template amplification followed by exome sequencing of neuronal DNA from the affected pool, unaffected pool, and saliva. The identified variant was validated using droplet digital polymerase chain reaction (PCR). RESULTS: An 11-year-old male with drug-resistant genetic-structural epilepsy due to left anterior insula FCD had seizures from age 3 years. Stereo EEG confirmed seizure onset in the left anterior insula. The two anterior insula electrodes were combined as the affected pool and three frontal electrodes as the unaffected pool. FANS isolated 140 neuronal nuclei from the affected and 245 neuronal nuclei from the unaffected pool. A novel somatic missense MTOR variant (p.Leu489Met, CADD score 23.7) was identified in the affected neuronal sample. Droplet digital PCR confirmed a mosaic gradient (variant allele frequency = .78% in affected neuronal sample; variant was absent in all other samples). SIGNIFICANCE: Our findings confirm that harvesting neuronal DNA from depth electrodes followed by molecular analysis to identify brain somatic variants is feasible. Our novel method represents a significant improvement compared to the previous method by focusing the analysis on high-quality cells of the cell type of interest.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7 mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

Regulation of VEGF-A expression and VEGF-A-targeted therapy in malignant tumors.

Vascular endothelial growth factor A (VEGF-A), a highly conserved dimeric glycoprotein, is a key regulatory gene and a marker molecule of angiogenesis. The upregulation of VEGF-A facilitates the process of tumor vascularization, thereby fostering the initiation and progression of malignant neoplasms. Many genes can adjust the angiogenesis of tumors by changing the expression of VEGF-A. In addition, VEGF-A also exhibits immune regulatory properties, which directly or indirectly suppresses the antitumor activity of immune cells. The emergence of VEGF-A-targeted therapy alone or in rational combinations has revolutionized the treatment of various cancers. This review discusses how diverse mechanisms in various tumors regulate VEGF-A expression to promote tumor angiogenesis and the role of VEGF-A in tumor immune microenvironment. The application of drugs targeting VEGF-A in tumor therapy is also summarized including antibody molecule drugs and traditional Chinese medicine.