Lithium tantalate photonic integrated circuits for volume manufacturing.

Electro-optical photonic integrated circuits (PICs) based on lithium niobate (LiNbO3) have demonstrated the vast capabilities of materials with a high Pockels coefficient1,2. They enable linear and high-speed modulators operating at complementary metal-oxide-semiconductor voltage levels3 to be used in applications including data-centre communications4, high-performance computing and photonic accelerators for AI5. However, industrial use of this technology is hindered by the high cost per wafer and the limited wafer size. The high cost results from the lack of existing high-volume applications in other domains of the sort that accelerated the adoption of silicon-on-insulator (SOI) photonics, which was driven by vast investment in microelectronics. Here we report low-loss PICs made of lithium tantalate (LiTaO3), a material that has already been adopted commercially for 5G radiofrequency filters6 and therefore enables scalable manufacturing at low cost, and it has equal, and in some cases superior, properties to LiNbO3. We show that LiTaO3 can be etched to create low-loss (5.6 dB m-1) PICs using a deep ultraviolet (DUV) stepper-based manufacturing process7. We demonstrate a LiTaO3 Mach-Zehnder modulator (MZM) with a half-wave voltage-length product of 1.9 V cm and an electro-optic bandwidth of up to 40 GHz. In comparison with LiNbO3, LiTaO3 exhibits a much lower birefringence, enabling high-density circuits and broadband operation over all telecommunication bands. Moreover, the platform supports the generation of soliton microcombs. Our work paves the way for the scalable manufacture of low-cost and large-volume next-generation electro-optical PICs.

Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-κB Activation and Protects against Inflammatory Responses.

The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/ß-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/ß-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses.

Eukaryotic AlaX provides multiple checkpoints for quality and quantity of aminoacyl-tRNAs in translation.

Translational fidelity relies critically on correct aminoacyl-tRNA supply. The trans-editing factor AlaX predominantly hydrolyzes Ser-tRNAAla, functioning as a third sieve of alanyl-tRNA synthetase (AlaRS). Despite extensive studies in bacteria and archaea, the mechanism of trans-editing in mammals remains largely unknown. Here, we show that human AlaX (hAlaX), which is exclusively distributed in the cytoplasm, is an active trans-editing factor with strict Ser-specificity. In vitro, both hAlaX and yeast AlaX (ScAlaX) were capable of hydrolyzing nearly all Ser-mischarged cytoplasmic and mitochondrial tRNAs; and robustly edited cognate Ser-charged cytoplasmic and mitochondrial tRNASers. In vivo or cell-based studies revealed that loss of ScAlaX or hAlaX readily induced Ala- and Thr-to-Ser misincorporation. Overexpression of hAlaX impeded the decoding efficiency of consecutive Ser codons, implying its regulatory role in Ser codon decoding. Remarkably, yeast cells with ScAlaX deletion responded differently to translation inhibitor treatment, with a gain in geneticin resistance, but sensitivity to cycloheximide, both of which were rescued by editing-capable ScAlaX, alanyl- or threonyl-tRNA synthetase. Altogether, our results demonstrated the previously undescribed editing peculiarities of eukaryotic AlaXs, which provide multiple checkpoints to maintain the speed and fidelity of genetic decoding.

Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy.

Proofreading (editing) of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs), whose impairment causes neurodegeneration and cardiac diseases, is of high significance for protein homeostasis. However, whether mitochondrial translation needs fidelity and the significance of editing by mitochondrial aaRSs have been unclear. Here, we show that mammalian cells critically depended on the editing of mitochondrial threonyl-tRNA synthetase (mtThrRS, encoded by Tars2), disruption of which accumulated Ser-tRNAThr and generated a large abundance of Thr-to-Ser misincorporated peptides in vivo. Such infidelity impaired mitochondrial translation and oxidative phosphorylation, causing oxidative stress and cell cycle arrest in the G0/G1 phase. Notably, reactive oxygen species (ROS) scavenging by N-acetylcysteine attenuated this abnormal cell proliferation. A mouse model of heart-specific defective mtThrRS editing was established. Increased ROS levels, blocked cardiomyocyte proliferation, contractile dysfunction, dilated cardiomyopathy, and cardiac fibrosis were observed. Our results elucidate that mitochondria critically require a high level of translational accuracy at Thr codons and highlight the cellular dysfunctions and imbalance in tissue homeostasis caused by mitochondrial mistranslation.

BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway.

The expression of large conductance calcium-activated potassium channels (BK channels) in adipose tissue has been identified for years. BK channel deletion can improve metabolism in vivo, but the relative mechanisms remain unclear. Here, we examined the effects of BK channels on the differentiation of adipose-derived stem cells (ADSCs) and the related mechanisms. BKα and ß1 subunits were expressed on adipocytes. We found that both deletion of the KCNMA1 gene, encoding the pore forming α subunit of BK channels, and the BK channel inhibitor paxilline increased the expression of key genes in the peroxisome proliferator activated receptor (PPAR) pathway and promoted adipogenetic differentiation of ADSCs. We also observed that the MAPK-ERK pathway participates in BK channel deficiency-promoted adipogenic differentiation of ADSCs and that ERK inhibitors blocked the differentiation-promoting effect of BK channel deficiency. Hyperplasia of adipocytes is considered beneficial for metabolic health. These results indicate that BK channels play an important role in adipose hyperplasia by regulating the differentiation of ADSCs and may become an important target for studying the pathogenesis and treatment strategies of metabolic disorder-related diseases.

Thickness-Dependent Magnetic Breakdown in ZrSiSe Nanoplates.

We report a study of thickness-dependent interband and intraband magnetic breakdown by thermoelectric quantum oscillations in ZrSiSe nanoplates. Under high magnetic fields of up to 30 T, quantum oscillations arising from degenerated hole pockets were observed in thick ZrSiSe nanoplates. However, when decreasing the thickness, plentiful multifrequency quantum oscillations originating from hole and electron pockets are captured. These multiple frequencies can be explained by the emergent interband magnetic breakdown enclosing individual hole and electron pockets and intraband magnetic breakdown within spin-orbit coupling (SOC) induced saddle-shaped electron pockets, resulting in the enhanced contribution to thermal transport in thin ZrSiSe nanoplates. These experimental frequencies agree well with theoretical calculations of the intriguing tunneling processes. Our results introduce a new member of magnetic breakdown to the field and open up a dimension for modulating magnetic breakdown, which holds fundamental significance for both low-dimensional topological materials and the physics of magnetic breakdown.

Gate-tunable Intrinsic Anomalous Hall Effect in Epitaxial MnBi2Te4 Films.

The anomalous Hall effect (AHE) is an important transport signature revealing topological properties of magnetic materials and their spin textures. Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator. However, the origin of its intriguing AHE behaviors remains elusive. Here, we demonstrate the Berry curvature-dominated intrinsic AHE in wafer-scale MnBi2Te4 films. By applying back-gate voltages, we observe an ambipolar conduction and n-p transition in ∼7-layer MnBi2Te4, where a quadratic relation between the AHE resistance and longitudinal resistance suggests its intrinsic AHE nature. In particular, for ∼3-layer MnBi2Te4, the AHE sign can be tuned from pristine negative to positive. First-principles calculations unveil that such an AHE reversal originated from the competing Berry curvature between oppositely polarized spin-minority-dominated surface states and spin-majority-dominated inner bands. Our results shed light on the underlying physical mechanism of the intrinsic AHE and provide new perspectives for the unconventional sign-tunable AHE.

Effects of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans on Modeling Subgingival Microbiome and Impairment of Oral Epithelial Barrier.

Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The polymicrobial synergy and dysbiosis hypothesis proposes a dynamic host-microbiome balance, with certain modulators capable of disrupting eubiosis and driving shifts towards dysbiosis within the community. However, these factors remain to be explored. We established a Porphyromonas gingivalis- or Aggregatibacter actinomycetemcomitans-modified subgingival microbiome model and 16S rRNA sequencing revealed that P. gingivalis and A. actinomycetemcomitans altered the microbiome structure and composition indicated by α and ß diversity metrics. P. gingivalis increased the subgingival dysbiosis index (SDI), while A. actinomycetemcomitans resulted in a lower SDI. Furthermore, P. gingivalis-stimulated microbiomes compromised epithelium function and reduced expression of tight junction proteins, whereas A. actinomycetemcomitans yielded mild effects. In conclusion, by inoculating P. gingivalis, we created dysbiotic microcosm biofilms in vitro resembling periodontitis-related subgingival microbiota, exhibiting enhanced dysbiosis and impaired epithelium integrity.

Effect of Curcuma longa extract on reproduction function in mice and testosterone production in Leydig cells.

Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our in vitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.

Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development.

Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 KO mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNAThrs were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex, suggesting that Tarsl2 is a peripheral member of the multiple tRNA synthetase complex. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development.

Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice.

Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6-8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1ß, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

Single-Atom Mn Catalysts via Integration with Mn Sub Nano-Clusters Synergistically Enhance Oxygen Reduction Reaction.

Integrating single atoms and clusters into one system represents a novel strategy for achieving the desired catalytic performance. In comparison to single-atom catalysts, catalysts combining single atoms and clusters harness the advantages of both, thus displaying greater potential. Nevertheless, constructing single-atom-cluster systems remains challenging, and the fundamental mechanism for enhancing catalytic activity remains elusive. In this study, a directly confined preparation of a 3D hollow sea urchin-like carbon structure (MnSA/MnAC-SSCNR) is developed. Mn single atoms synergistically interact with Mn clusters, optimizing and reducing energy barriers in the reaction pathway, thus enhancing reaction kinetics. Consequently, in contrast to Mn single-atom catalysts (MnSA-SSCNR), MnSA/MnAC-SSCNR exhibits significantly improved oxygen reduction activity, with a half-wave potential (E1/2) of 0.90 V in 0.1 m KOH, surpassing that of MnSA-SSCNR and Pt/C. This work demonstrates a strategy of remote synergy between heterogeneous single atoms and clusters, which not only contributes to electrocatalytic reactions but also holds potential for reactions involving more complex products.

Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

Circulation pattern and genetic variation of rhinovirus infection among hospitalized children on Hainan Island, before and after the dynamic zero-COVID policy, from 2021 to 2023.

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.

Development and application of a deep learning-based comprehensive early diagnostic model for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a frequently diagnosed yet treatable condition, provided it is identified early and managed effectively. This study aims to develop an advanced COPD diagnostic model by integrating deep learning and radiomics features. METHODS: We utilized a dataset comprising CT images from 2,983 participants, of which 2,317 participants also provided epidemiological data through questionnaires. Deep learning features were extracted using a Variational Autoencoder, and radiomics features were obtained using the PyRadiomics package. Multi-Layer Perceptrons were used to construct models based on deep learning and radiomics features independently, as well as a fusion model integrating both. Subsequently, epidemiological questionnaire data were incorporated to establish a more comprehensive model. The diagnostic performance of standalone models, the fusion model and the comprehensive model was evaluated and compared using metrics including accuracy, precision, recall, F1-score, Brier score, receiver operating characteristic curves, and area under the curve (AUC). RESULTS: The fusion model exhibited outstanding performance with an AUC of 0.952, surpassing the standalone models based solely on deep learning features (AUC = 0.844) or radiomics features (AUC = 0.944). Notably, the comprehensive model, incorporating deep learning features, radiomics features, and questionnaire variables demonstrated the highest diagnostic performance among all models, yielding an AUC of 0.971. CONCLUSION: We developed and implemented a data fusion strategy to construct a state-of-the-art COPD diagnostic model integrating deep learning features, radiomics features, and questionnaire variables. Our data fusion strategy proved effective, and the model can be easily deployed in clinical settings. TRIAL REGISTRATION: Not applicable. This study is NOT a clinical trial, it does not report the results of a health care intervention on human participants.

Interleukin-2 enhancer binding factor 2 negatively regulates the replication of duck hepatitis A virus type 1 by disrupting the RNA-dependent RNA polymerase activity of 3D polymerase.

The interaction between viral components and cellular proteins plays a crucial role in viral replication. In a previous study, we showed that the 3'-untranslated region (3'-UTR) is an essential element for the replication of duck hepatitis A virus type 1 (DHAV-1). However, the underlying mechanism is still unclear. To gain a deeper understanding of this mechanism, we used an RNA pull-down and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay to identify new host factors that interact with the 3'-UTR. We selected interleukin-2 enhancer binding factor 2 (ILF2) for further analysis. We showed that ILF2 interacts specifically with both the 3'-UTR and the 3D polymerase (3Dpol) of DHAV-1 through in vitro RNA pull-down and co-immunoprecipitation assays, respectively. We showed that ILF2 negatively regulates viral replication in duck embryo fibroblasts (DEFs), and that its overexpression in DEFs markedly suppresses DHAV-1 replication. Conversely, ILF2 silencing resulted in a significant increase in viral replication. In addition, the RNA-dependent RNA polymerase (RdRP) activity of 3Dpol facilitated viral replication by enhancing viral RNA translation efficiency, whereas ILF2 disrupted the role of RdRP in viral RNA translation efficiency to suppress DHAV-1 replication. At last, DHAV-1 replication markedly suppressed the expression of ILF2 in DEFs, duck embryo hepatocytes, and different tissues of 1 day-old ducklings. A negative correlation was observed between ILF2 expression and the viral load in primary cells and different organs of young ducklings, suggesting that ILF2 may affect the viral load both in vitro and in vivo.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Design and preparation of an artificial vascular scaffold with internal surface modification.

BACKGROUND: Advances in regeneration methods have brought us improved vascular scaffolds with small diameters (φ < 6 mm) for enhancing biological suitability that solve their propensity for causing intimal hyperplasia post-transplantation. METHODS: The correlation between the rehydration ratio of the hydrogel and its material concentration is obtained by adjusting the material ratio of the hydrogel solution. The vascular model with helical structure has been established and analyzed to verify the effect of helical microvascular structure on thrombosis formation by the fluid simulation methods. Then, the helical structure vascular has been fabricated by self-developed 3D bioprinter, the vascular scaffolds are freeze-dried and rehydrated in polyethylene glycol (PEG) solution. RESULTS: The experimental results showed that the hybrid hydrogel had a qualified rehydration ratio when the content of gelatin, sodium alginate, and glycerol was 5, 6, and 3 wt%. The established flow channel model can effectively reduce thrombus deposition and improve long-term patency ratio. After PEG solution modification, the contact angle of the inner wall of the vascular scaffold was less than 30°, showing better hydrophilic characteristics. CONCLUSION: In study, a small-diameter inner wall vascular scaffold with better long-term patency was successfully designed and prepared by wrinkling and PEG modification of the inner wall of the vascular scaffold. This study not only creates small-diameter vascular scaffolds with helical structure that improves the surface hydrophilicity to reduce the risk of thrombosis but also rekindles confidence in the regeneration of small caliber vascular structures.

The critical role of SETDB1-mediated CCND1/PI3K/AKT pathway via p53-RS di-methylation at K370 in the proliferation of WRL68 cells induced by nicotine.

Constituents of cigarette smoke are known to be carcinogens. Additionally, there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Nicotine, the primary constituent of tobacco, plays a role in cancer progression. In our previous study, it was found that nicotine enhances the proliferation of a human normal fetal hepatic (WRL68) cell due to the activation of p53 mutation at Ser249 (p53-RS)/STAT1/CCND1 signaling pathway. Here, we further elucidated the mechanism of regulating this pathway. Firstly, dose-dependent increase of SETDB1 protein level in WRL68 cells upon exposure to nicotine (1.25, 2.5, and 5 µM), significantly enhanced cellular proliferation. In addition, the upregulation of SETDB1 protein was necessary for the nuclear translocation of p53-RS to establish a ternary complex with STAT1 and SETDB1, which facilitated p53-RS di-methylation at K370 (p53-RS/K370me2). After that, the activation of CCND1/PI3K/AKT pathway was initiated when STAT1 stability was enhanced by p53-RS/K370me2, ultimately resulting in cell proliferation. Altogether, the study revealed that the increase in SETDB1 expression could potentially have a significant impact on the activation of CCND1/PI3K/AKT pathway through p53-RS/K370me2, leading to the proliferation of WRL68 cells induced by nicotine, which could contribute to hepatocellular carcinoma for smokers. Besides, the results of this study provided a foundation for the development of anticancer therapies for cancers associated with tobacco use.

Nondegenerate Integer Quantum Hall Effect from Topological Surface States in Ag2Te Nanoplates.

The quantum Hall effect is one of the exclusive properties displayed by Dirac Fermions in topological insulators, which propagates along the chiral edge state and gives rise to quantized electron transport. However, the quantum Hall effect formed by the nondegenerate Dirac surface states has been elusive so far. Here, we demonstrate the nondegenerate integer quantum Hall effect from the topological surface states in three-dimensional (3D) topological insulator ß-Ag2Te nanostructures. Surface-state dominant conductance renders quantum Hall conductance plateaus with a step of e2/h, along with typical thermopower behaviors of two-dimensional (2D) massless Dirac electrons. The 2D nature of the topological surface states is proven by the electrical and thermal transport responses under tilted magnetic fields. Moreover, the degeneracy of the surface states is removed by structure inversion asymmetry (SIA). The evidenced SIA-induced nondegenerate integer quantum Hall effect in low-symmetry ß-Ag2Te has implications for both fundamental study and the realization of topological magneto-electric effects.