Muscone restores anoikis sensitivity in TMZ-resistant glioblastoma cells by suppressing TOP2A via the EGFR/Integrin ß1/FAK signaling pathway.

BACKGROUND: Temozolomide (TMZ) resistance is the main obstacle faced by glioblastoma multiforme (GBM) treatment. Muscone, one of the primary active pharmacological ingredients of Shexiang (Moschus), can cross the blood-brain barrier (BBB) and is being investigated as an antineoplastic medication. However, muscone treatment for GBM has received little research, and its possible mechanisms are still unclear. PURPOSE: This study aims to evaluate the effect and the potential molecular mechanism of muscone on TMZ-resistant GBM cells. METHODS: The differentially expressed genes (DEGs) between TMZ-resistant GBM cells and TMZ-sensitive GBM cells were screened using GEO2R. By progressively raising the TMZ concentration, a relatively stable TMZ-resistant human GBM cell line was established. The drug-resistance traits of U251-TR cells were assessed via the CCK-8 assay and Western Blot analysis of MGMT and TOP2A expression. Cell viability, cell proliferation, cell migration ability, and drug synergism were detected by the CCK-8 assay, colony formation assay, wound healing assay, and drug interaction relationship test, respectively. Anoikis was quantified by Calcein-AM/EthD-1 staining, MTT assay, and flow cytometry. Measurements of cell cycle arrest, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed using cell cycle staining, Annexin V-FITC/PI labeling, JC-1 assay, and ROS assay, respectively. DNA damage was measured by TUNEL assay, alkaline comet assay, and γ-H2AX foci assay. GEPIA was used to investigate the link between the anoikis marker (FAK)/drug resistance gene and critical proteins in the EGFR/Integrin ß1 signaling pathway. Molecular docking was used to anticipate the probable targets of muscone. The intracellular co-localization and expression of EGFR and FAK were shown using immunofluorescence. The U251-TR cell line stably overexpressing EGFR was constructed using lentiviral transduction to assess the involvement of EGFR-related signaling in anoikis resistance. Western Blot was employed to detect the expression of migration-related proteins, cyclins, anoikis-related proteins, DNA damage/repair-related proteins, and associated pathway proteins. RESULTS: DEGs analysis identified 97 deregulated chemotherapy-resistant genes and 3779 upregulated genes in TMZ-resistant GBM cells. Subsequent experiments verified TMZ resistance and the hyper-expression of DNA repair-related genes (TOP2A and MGMT) in continuously low-dose TMZ-induced U251-TR cells. Muscone exhibited dose-dependent inhibition of U251-TR cell migration and proliferation, and its co-administration with TMZ showed the potential for enhanced therapeutic efficacy. By downregulating FAK, muscone reduced anoikis resistance in anchorage-independent U251-TR cells. It also caused cell cycle arrest in the G2/M phase by upregulating p21 and downregulating CDK1, CDK2, and Cyclin E1. Muscone-induced anoikis was accompanied by mitochondrial membrane potential collapse, ROS production, an increase in the BAX/Bcl-2 ratio, as well as elevated levels of Cytochrome c (Cyt c), cleaved caspase-9, and cleaved caspase-3. These findings indicated that muscone might trigger mitochondrial-dependent anoikis via ROS generation. Moreover, significant DNA damage, DNA double-strand breaks (DSBs), the formation of γ-H2AX foci, and a reduction in TOP2A expression are also associated with muscone-induced anoikis. Overexpression of EGFR in U251-TR cells boosted the expression of Integrin ß1, FAK, ß-Catenin, and TOP2A, whereas muscone suppressed the expression levels of EGFR, Integrin ß1, ß-Catenin, FAK, and TOP2A. Muscone may influence the expression of the key DNA repair enzyme, TOP2A, by suppressing the EGFR/Integrin ß1/FAK pathway. CONCLUSION: We first demonstrated that muscone suppressed TOP2A expression through the EGFR/Integrin ß1/FAK pathway, hence restoring anoikis sensitivity in TMZ-resistant GBM cells. These data suggest that muscone may be a promising co-therapeutic agent for enhancing GBM treatment, particularly in cases of TMZ-resistant GBM with elevated TOP2A expression.

A prospective and randomized study comparing ultrasound-guided real time injection to conventional blind injection of botulinum neurotoxin for glabellar wrinkles.

BACKGROUND: Botulinum neurotoxin injections are the most frequently performed cosmetic procedures, but conventional blind injection for glabellar wrinkles remains to have some limitations. AIMS: We intend to directly inject botulinum neurotoxin into the glabella complex guided by real time ultrasound. We aim to propose a more efficient and safer botulinum neurotoxin injection strategy for glabellar wrinkles. METHODS: A total of 40 subjects with moderate to severe glabellar lines were enrolled in this study to receive botulinum neurotoxin injection, either through ultrasound-guided real time injection or conventional blind injection. Facial Wrinkle Scale (ranging from 0 = none to 3 = severe) and inter-brow distance (from 3D scanned face images) were used to evaluate the glabellar wrinkles improvement. Paired t test and two-sample t test were performed to analyze the within-group and between-group differences. RESULTS: The wrinkle score reduction was significant (p < 0.0001) immediately after the injection in ultrasound-guided injection group, but not in blind injection group (p = 0.163). Ultrasound-guided injection also showed a higher performance of wrinkle score reduction and more effective inter-brow distance increase over blind injection at Day 0 (p < 0.0001), Day 1 (p < 0.0001), Day 21 (p < 0.01) and Day 35 (p < 0.01) after initial treatment. CONCLUSIONS: The results of the study confirmed that botulinum neurotoxin injection for glabellar wrinkles under ultrasound guidance achieves quicker onset of action and better final outcomes compared to conventional blind injection.

Semi or fully automatic tooth segmentation in CBCT images: a review.

Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.

Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An open-label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study was aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label randomized, nonplacebo-controlled clinical study. The Numerical Rating Scale (NRS) scores in the FMT group were slightly lower than the control group at 1 month (P> 0.05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < 0.001). Besides, compared with the control group, the Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scores were significantly lower in the FMT group at different time points (P < 0.001). After 6 months of treatment, there was a significant increase in serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels (P < 0.001), while glutamate levels significantly decreased in the FMT group (P < 0.001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < 0.05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes of neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: Fecal microbiota transplantation (FMT) is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Contrastive Multiview Attribute Graph Clustering With Adaptive Encoders.

Multiview attribute graph clustering aims to cluster nodes into disjoint categories by taking advantage of the multiview topological structures and the node attribute values. However, the existing works fail to explicitly discover the inherent relationships in multiview topological graph matrices while considering different properties between the graphs. Besides, they cannot well handle the sparse structure of some graphs in the learning procedure of graph embeddings. Therefore, in this article, we propose a novel contrastive multiview attribute graph clustering (CMAGC) with adaptive encoders method. Within this framework, the adaptive encoders concerning different properties of distinct topological graphs are chosen to integrate multiview attribute graph information by checking whether there exists high-order neighbor information or not. Meanwhile, the number of layers of the GCN encoders is selected according to the prior knowledge related to the characteristics of different topological graphs. In particular, the feature-level and cluster-level contrastive learning are conducted on the multiview soft assignment representations, where the union of the first-order neighbors from the corresponding graph pairs is regarded as the positive pairs for data augmentation and the sparse neighbor information problem in some graphs can be well dealt with. To the best of our knowledge, it is the first time to explicitly deal with the inherent relationships from the interview and intraview perspectives. Extensive experiments are conducted on several datasets to verify the superiority of the proposed CMAGC method compared with the state-of-the-art methods.

Genome Mining Reveals a UbiA-Type Prenyltransferase Access to Farnesylation of Diketopiperazines.

UbiA-type prenyltransferases (PTases) are significant enzymes that lead to structurally diverse meroterpenoids. Herein, we report the identification and characterization of an undescribed UbiA-type PTase, FtaB, that is responsible for the farnesylation of indole-containing diketopiperazines (DKPs) through genome mining. Heterologous expression of the fta gene cluster and non-native pathways result in the production of a series of new C2-farnesylated DKPs. This study broadens the reaction scope of UbiA-type PTases and expands the chemical diversity of meroterpenoids.

Rapid detection of melamine by DNA Walker mediated SERS sensing technique based on signal amplification function.

A new method is proposed for detecting typical melamine dopants in food using surface-enhanced Raman scattering (SERS) biosensing technology. Melamine specific aptamer was used as the identification probe, and gold magnets (AuNPs@MNPs) and small gold nanoparticles (AuNPs@MBA) were used as the basis for Raman detection. The Raman signal of the detection system can directly detect melamine quantitatively. Under optimized conditions, the detection of melamine was carried out in the low concentration range of 0.001-500 mg/kg, the enhancement factor (EF) was 2.3 × 107, and the detection limit was 0.001 mg/kg. The method is sensitive and rapid, and can be used for the rapid detection of melamine in the field environment.

The effects of different types of Tai Chi exercises on preventing falls in older adults: a systematic review and network meta-analysis.

OBJECTIVES: Few studies comparing the effects of different types of Tai Chi exercises on preventing falls in older adults. We compared the effects for finding an optimal intervention. METHODS: We searched 12 databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and so on, from their inception to January 13, 2023. Randomized controlled trials incorporating different types of Tai Chi for preventing falls in older adults were included. The outcome measures were the incidence of falls and Berg Balance Scale (BBS). Network meta-analysis (NMA) was conducted using Stata 15.1 based on a frequentist framework. RESULTS: Seventeen trials were eligible, including 3470 participants and four types of Tai Chi. They were 24-form simplified Tai Chi (24-form), Yang style Tai Chi (Yang style), Sun style Tai Chi (Sun style) and Tai Chi exercise program (TCEP). In paired meta-analysis, for incidence of falls, 24-form (Relative Risk (RR) = 0.59, 95% confidence interval (CI) [0.40, 0.86]) was more efficient than the control group. For BBS outcome, 24-form (MD (mean difference) = 2.32, 95% CI [1.42, 3.22]) was better than the control group. In the NMA, the results of incidence of falls were as follows: 24-form > Yang style > Sun style > control > TCEP. The rank probability of BBS was as follows: 24-form > TCEP > Yang style > control. CONCLUSION: Among the four types of Tai Chi studied, the 24-form simplified Tai Chi has shown better efficacy than other types.

Developmental Dopaminergic Signaling Modulates Neural Circuit Formation and Contributes to Autism Spectrum Disorder-Related Phenotypes.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, it remains unclear whether and how disrupted dopaminergic signaling during development contributes to ASD. In this study, human brain RNA sequencing transcriptome analysis revealed a significant correlation between changes in dopaminergic signaling pathways and neural developmental signaling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signaling led to neural circuit abnormalities and behavior reminiscent of autism. Dopaminergic signaling may impact neuronal specification by potentially modulating integrins. These findings shed light on the mechanisms underlying the link between disrupted developmental dopamine signaling and ASD, and they point to the possibility of targeting dopaminergic signaling in early development for ASD treatment.

Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study.

Background: Current therapeutic measures for thyroid dysfunction are limited and often accompanied by adverse effects. The use of lipid-lowering drugs like statins has recently been associated with lower thyroid eye diseases risk. Objective: To investigate the implications of genetically proxied lipid-lowering drugs on thyroid dysfunction. Methods: In this drug-target Mendelian randomization (MR) study, we utilized genetic variants within drug target genes associated with low-density lipoprotein (LDL) or triglyceride (TG), derived from a genome-wide association study (GWAS) meta-analysis (N ≤ 188,577), to simulate lifelong drug interventions. Genetic summary statistics for thyroid dysfunction outcomes were retrieved from GWAS datasets of Thyroid Omics Consortium (N ≤ 54,288) and UK Biobank (N = 484,598). Inverse-variance-weighted MR (IVW-MR) method was performed as primary analysis, followed by validation in colocalization analysis. A subsequent two-step MR analysis was conducted to identify biomarkers mediating the identified drug-outcome association. Results: In IVW-MR analysis, genetic mimicry of 3-hydroxy-3-methylglutarylcoenzyme reductase (HMGCR) inhibitors (e.g. statins) was significantly associated with lower risk of hyperthyroidism in two independent datasets (OR1, 0.417 per 1-mmol/L lower in LDL-C; 95% CI 0.262 to 0.664; P1 = 2.262 × 10-4; OR2 0.996; 95% CI 0.993-0.998; P2 = 0.002). Two-step MR analysis revealed eighteen biomarkers linked to genetic mimicry of HMGCR inhibition, and identified insulin-like growth factor 1 (IGF-1) levels mediating 2.108% of the negative causal relationship between HMGCR inhibition and hyperthyroidism. Conclusion: This study supports HMGCR inhibition as a promising therapeutic strategy for hyperthyroidism and suggests its underlying mechanisms may extend beyond lipid metabolism. Further investigations through laboratory studies and clinical trials are necessary to confirm and elucidate these findings.

Unveiling characteristic metabolic accumulation over enzymatic-catalyzed process of Tieguanyin oolong tea manufacturing by DESI-MSI and multiple-omics.

To achieve an integrative understanding of the spatial distribution and chronological flavoring compounds accumulation, desorption-electrospray-ionization coupled mass-spectrometry-imaging (DESI-MSI) and multi-omics techniques were performed on the leaf samples collected from the enzymatic-catalyzed-process (ECP) stage of Tieguanyin oolong tea manufacturing. The result of DESI-MSI visualization indicated transform or re-distribution of catechins, flavonols and amino acids were on-going attributing to the multi-stress over ECP stage. Out of identified 2621 non-volatiles and 45,771 transcripts, 43 non-volatiles and 12 co-expressed pathways were screened out as biomarkers and key cascades in response to adverse conditions. The targeted metabolic analysis on the characteristic flavoring compounds showed that the accumulations of free amino acids were enhanced, while catechins, flavonol glycosides, and alkaloids exhibited dynamic changes. This result suggests withering and turning-over process are compatible and collectively regulate the metabolic accumulation and development of flavoring metabolites, facilitating to the development of characteristic quality of Tieguanyin tea.

NAMPT/NAD+/PARP1 Pathway Regulates CFA-Induced Inflammatory Pain via NF-κB Signaling in Rodents.

Emerging evidence has implicated nicotinamide adenine dinucleotide (NAD+) metabolism in various inflammatory diseases. In the study, the role of NAD+ metabolism in Complete Freund's Adjuvant (CFA)-evoked inflammatory pain and the underlying mechanisms are investigated. The study demonstrated that CFA induced upregulation of nicotinamide phosphoribosyltransferase (NAMPT) in dorsal root ganglia (DRG) without significant changes in the spinal cord. Inhibition of NAMPT expression by intrathecal injection of NAMPT siRNA alleviated CFA-induced pain-like behavior, decreased NAD+ contents in DRG, and lowered poly-(ADP-ribose) polymerase 1 (PARP1) activity levels. These effects are all reversed by the supplement of nicotinamide mononucleotide (NMN). Inhibition of PARP1 expression by intrathecal injection of PARP1 siRNA alleviated CFA-induced pain-like behavior, while elevated NAD+ levels of DRG. The analgesic effect of inhibiting NAMPT/NAD+/PARP1 axis can be attributed to the downregulation of the NF-κB/IL-1ß inflammatory pathway. Double immunofluorescence staining showed that the expression of NAMPT/NAD+/PARP1 axis is restricted to DRG neurons. In conclusion, PARP1 activation in response to CFA stimulation, fueled by NAMPT-derived NAD+, mediates CFA-induced inflammatory pain through NF-κB/IL-1ß inflammatory pathway.

Motif-Based Contrastive Learning for Community Detection.

Community detection has become a prominent task in complex network analysis. However, most of the existing methods for community detection only focus on the lower order structure at the level of individual nodes and edges and ignore the higher order connectivity patterns that characterize the fundamental building blocks within the network. In recent years, researchers have shown interest in motifs and their role in network analysis. However, most of the existing higher order approaches are based on shallow methods, failing to capture the intricate nonlinear relationships between nodes. In order to better fuse higher order and lower order structural information, a novel deep learning framework called motif-based contrastive learning for community detection (MotifCC) is proposed. First, a higher order network is constructed based on motifs. Subnetworks are then obtained by removing isolated nodes, addressing the fragmentation issue in the higher order network. Next, the concept of contrastive learning is applied to effectively fuse various kinds of information from nodes, edges, and higher order and lower order structures. This aims to maximize the similarity of corresponding node information, while distinguishing different nodes and different communities. Finally, based on the community structure of subnetworks, the community labels of all nodes are obtained by using the idea of label propagation. Extensive experiments on real-world datasets validate the effectiveness of MotifCC.

Citric Acid Promotes Immune Function by Modulating the Intestinal Barrier.

Amidst increasing concern about antibiotic resistance resulting from the overuse of antibiotics, there is a growing interest in exploring alternative agents. One such agent is citric acid, an organic compound commonly used for various applications. Our research findings indicate that the inclusion of citric acid can have several beneficial effects on the tight junctions found in the mouse intestine. Firstly, the study suggests that citric acid may contribute to weight gain by stimulating the growth of intestinal epithelial cells (IE-6). Citric acid enhances the small intestinal villus-crypt ratio in mice, thereby promoting intestinal structural morphology. Additionally, citric acid has been found to increase the population of beneficial intestinal microorganisms, including Bifidobacterium and Lactobacillus. It also promotes the expression of important protein genes such as occludin, ZO-1, and claudin-1, which play crucial roles in maintaining the integrity of the tight junction barrier in the intestines. Furthermore, in infected IEC-6 cells with H9N2 avian influenza virus, citric acid augmented the expression of genes closely associated with the influenza virus infection. Moreover, it reduces the inflammatory response caused by the viral infection and thwarted influenza virus replication. These findings suggest that citric acid fortifies the intestinal tight junction barrier, inhibits the replication of influenza viruses targeting the intestinal tract, and boosts intestinal immune function.

A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges.

Shingles is caused by the reactivation of varicella zoster virus (VZV) and manifests as painful skin rashes. While the recombinant protein-based vaccine proves highly effective, it encounters supply chain challenges due to a shortage of the necessary adjuvant. Messenger RNA (mRNA)-based vaccines can be rapidly produced on a large scale, but their effectiveness relies on efficient delivery and sequence design. Here, an mRNA-based VZV vaccine using a synergistic lipid nanoparticle (Syn-LNP) containing two different ionizable lipids is developed. Syn-LNP shows superior mRNA expression compared to LNPs formulated with either type of ionizable lipid and to a commercialized LNP. After encapsulating VZV glycoprotein E (gE)-encoding mRNA, mgE@Syn-LNP induces robust humoral and cellular immune responses in two strains of mice. The magnitude of these responses is similar to that induced by adjuvanted recombinant gE proteins and significantly higher than that observed with live-attenuated VZV. mgE@Syn-LNP exhibits durable humoral responses for over 7 months without obvious adverse effects. In addition, mgE@Syn-LNP protects vaccinated guinea pigs against live VZV challenges. Preliminary studies on the mRNA antigen design reveal that the removal of glycosylation sites of gE greatly reduces its immune responses. Collectively, Syn-LNP encapsulating gE-encoded mRNA holds great promise as a shingles vaccine.

Efficient Low-temperature Hydrogen Production by Electrochemical-assisted Methanol Steam Reforming.

Methanol steam reforming (MSR) provides an alternative way for efficient production and safe transportation of hydrogen but requires harsh conditions and complicated purification processes. In this work, an efficient electrochemical-assisted MSR reaction for pure H2 production at lower temperature (~140 °C) is developed by coupling the electrocatalysis reaction into the MSR in a polymer electrolyte membrane electrolysis reactor. By electrochemically assisted, the two critical steps including the methanol dehydrogenation and water-gas shift reaction are accelerated, which is attributed to decreasing the methanol dehydrogenation energy and promoting the dissociation of H2 O to OH* by the applied potential. Furthermore, the reduced H2 partial pressure by the hydrogen oxidation and reduction process further promotes MSR. The combination of these advantages not only efficiently decreases the MSR temperature but also achieves the high rate of hydrogen production of 505 mmol H2 g Pt -1 h-1 with exceptionally high H2 selectivity (99 %) at 180 °C and a low voltage (0.4 V), and the productivity is about 30-fold than that of traditional MSR. This study opens up a new avenue to design novel electrolysis cells for hydrogen production.

BRT: An Efficient and Scalable Blockchain-Based Revocation Transparency System for TLS Connections.

Log-based public key infrastructure(PKI) refers to a robust class of CA-attack-resilient PKI that enhance transparency and accountability in the certificate revocation and issuance process by compelling certificate authorities (CAs) to submit revocations to publicly and verifiably accessible logs. However, log-based PKIs suffer from a reliance on centralized and consistent sources of information, rendering them susceptible to split-world attacks, and they regrettably fail to provide adequate incentives for recording or monitoring CA behavior. Blockchain-based PKIs address these limitations by enabling decentralized log audits through automated financial incentives. However, they continue to face challenges in developing a scalable revocation mechanism suited for lightweight clients. In this paper, we introduce BRT, a scalable blockchain-based system for certificate and revocation transparency. It serves to log, audit, and validate the status of certificates within the transport layer security (TLS)/secure sockets layer(SSL) PKI domain. We designed an audit-on-chain framework, coupled with an off-chain storage/computation system, to enhance the efficiency of BRT when operating in a blockchain environment. By implementing a blockchain-based prototype, we demonstrate that BRT achieves storage-efficient log recording with a peak compression rate reaching 8%, cost-effective log updates for large-scale certificates, and near-instantaneous revocation checks for users.

An integrated metabolomic and transcriptomic analysis reveals the dynamic changes of key metabolites and flavor formation over Tieguanyin oolong tea production.

To interpret the formation characteristic flavor during oolong tea manufacturing process, the dynamic changes of key flavor components in samples from various processing steps of Tieguanyin oolong tea production were investigated using widely-targeted metabolomic and the transcriptomic approaches. As a result, a total of 1078 metabolites were determined, of which 62 compounds were identified as biomarkers significantly changed over the manufacturing process. Quantitative determination of the total 50,343 transcripts showed 7480 of them were co-expressed different genes. Glutamic acid served as a critical metabolism hub and a signaling molecule for diverse stress responses. Additionally, the targeted quantification results showed that the contents of catechins and xanthine alkaloids in dried tea were dramatically decreased by 20.19% and 7.15% respectively than those in fresh leaves, which potentially contributed to the alleviation of astringent or bitter palates, promoting the characteristic mellow and rich flavor of Tieguanyin oolong tea.

Two-dimensional superhard silicon nitrides with widely tunable bandgap, high carrier mobility and hole-doping-induced robust magnetism.

The search for new forms of the traditional bulk materials to enrich their interactions and properties is an attractive subject in two-dimensional (2D) materials. In this work, novel tetra-hexa-mixed coordinated 2D silicon nitrides (Si3N4) and their analogues are systematically investigated via density functional theory. The results show the global minimum 2D structure, Si3N4 (T-aa), is a highly chemically and thermally stable superhard semiconductor with a wide indirect bandgap (about 6.0 eV), which is widely adjustable under both biaxial strain and vertical electric field. It also possesses anisotropic high carrier mobility, up to 5490 cm2 V-1 s-1 at room temperature. Besides, its nitride analogues of group IVA (Si, Ge, Sn, and Pb) exhibit diverse electronic structures with regular bandgap distribution. Remarkably, some nitride analogues display linearly increasing robust magnetism with hole doping. The theoretical Curie temperatures of Si3N4 and Sn3N4 with hole doping (1h+ per unit cell) are 298 and 180 K, respectively. The Si3N4 (T-aa) and its analogues have a variety of excellent properties to be potentially applied in various fields, e.g., semiconductor electronics, spintronics, high-temperature structural materials, and superhard materials.

Independent and Combined Associations of Blood Manganese, Cadmium and Lead Exposures with the Systemic Immune-Inflammation Index in Adults.

Manganese (Mn), cadmium (Cd) and lead (Pb) have toxic effects on the immune system. However, their independent and combined effects on immune-inflammation responses are unclear. In recent years, the systemic immune-inflammation index (SII) has been developed as an integrated and novel inflammatory indicator. A retrospective cross-sectional study of 2174 adults ≥20 years old from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 was conducted. Generalized linear models were used to evaluate the independent and combined associations of SII with blood Mn, Cd and Pb levels. As continuous variables, both blood Cd and Mn showed dose-dependent relationships with the SII before and after adjusting for all potential confounding factors. Metal concentrations were then converted into categorical variables. Compared with the adults in the lowest Cd or Mn tertile, those in the highest tertile had higher risks of elevated SII. Furthermore, co-exposure to Mn and Cd also showed a positive relationship with the SII after adjusting for all confounding factors. However, the single effect of Pb exposure and the joint effect of Pb and other metal exposures on the SII were not observed. This study provides important epidemiological evidence of the associations of SII with single and co-exposure effects of blood Mn, Cd, and Pb.