A continuum of zinc finger transcription factor retention on native chromatin underlies dynamic genome organization.

Transcription factor (TF) residence on chromatin translates into quantitative transcriptional or structural outcomes on genome. Commonly used formaldehyde crosslinking fixes TF-DNA interactions cumulatively and compromises the measured occupancy level. Here we mapped the occupancy level of global or individual zinc finger TFs like CTCF and MAZ, in the form of highly resolved footprints, on native chromatin. By incorporating reinforcing perturbation conditions, we established S-score, a quantitative metric to proxy the continuum of CTCF or MAZ retention across different motifs on native chromatin. The native chromatin-retained CTCF sites harbor sequence features within CTCF motifs better explained by S-score than the metrics obtained from other crosslinking or native assays. CTCF retention on native chromatin correlates with local SUMOylation level, and anti-correlates with transcriptional activity. The S-score successfully delineates the otherwise-masked differential stability of chromatin structures mediated by CTCF, or by MAZ independent of CTCF. Overall, our study established a paradigm continuum of TF retention across binding sites on native chromatin, explaining the dynamic genome organization.

Single-Mode Control and Individual Nanoparticle Detection in the Ultraviolet Region Based on Boron Nitride Microdisk with Whispering Gallery Mode.

Optical microcavities are known for their strongly enhanced light-matter interactions. Whispering gallery mode (WGM) microresonators have important applications in nonlinear optics, single-mode output, and biosensing. However, there are few studies on resonance modes in the ultraviolet spectrum because most materials with high absorption properties are in the ultraviolet band. In this study, the performance of a microdisk cavity based on boron nitride (BN) was simulated by using the Finite-difference time-domain (FDTD) method. The WGM characteristics of a single BN microdisk with different sizes were obtained, wherein the resonance modes could be regulated from 270 nm to 350 nm; additionally, a single-mode at 301.5 nm is achieved by cascading multiple BN microdisk cavities. Moreover, we found that a BN microdisk with a diameter of 2 µm has a position-independent precise sensitivity for the nanoparticle of 140 nm. This study provides new ideas for optical microcavities to achieve single-mode management and novel coronavirus size screening, such as SARS-CoV-2, in the ultraviolet region.

Uncovering the roles of DNA hemi-methylation in transcriptional regulation using MspJI-assisted hemi-methylation sequencing.

Hemi-methylated cytosine dyads widely occur on mammalian genomic DNA, and can be stably inherited across cell divisions, serving as potential epigenetic marks. Previous identification of hemi-methylation relied on harsh bisulfite treatment, leading to extensive DNA degradation and loss of methylation information. Here we introduce Mhemi-seq, a bisulfite-free strategy, to efficiently resolve methylation status of cytosine dyads into unmethylation, strand-specific hemi-methylation, or full-methylation. Mhemi-seq reproduces methylomes from bisulfite-based sequencing (BS-seq & hpBS-seq), including the asymmetric hemi-methylation enrichment flanking CTCF motifs. By avoiding base conversion, Mhemi-seq resolves allele-specific methylation and associated imprinted gene expression more efficiently than BS-seq. Furthermore, we reveal an inhibitory role of hemi-methylation in gene expression and transcription factor (TF)-DNA binding, and some displays a similar extent of inhibition as full-methylation. Finally, we uncover new hemi-methylation patterns within Alu retrotransposon elements. Collectively, Mhemi-seq can accelerate the identification of DNA hemi-methylation and facilitate its integration into the chromatin environment for future studies.

Laplacian Projection Based Global Physical Prior Smoke Reconstruction.

We present a novel framework for reconstructing fluid dynamics in real-life scenarios. Our approach leverages sparse view images and incorporates physical priors across long series of frames, resulting in reconstructed fluids with enhanced physical consistency. Unlike previous methods, we utilize a differentiable fluid simulator (DFS) and a differentiable renderer (DR) to exploit global physical priors, reducing reconstruction errors without the need for manual regularization coefficients. We introduce divergence-free Laplacian eigenfunctions (div-free LE) as velocity bases, improving computational efficiency and memory usage. By employing gradient-related strategies, we achieve better convergence and superior results. Extensive experiments demonstrate the effectiveness of our method, showcasing improved reconstruction quality and computational efficiency compared to existing approaches. We validate our approach using both synthetic and real data, highlighting its practical potential.

Enhancing wound healing and overcoming cisplatin resistance in ovarian cancer.

Ovarian cancer (OC) poses significant oncological challenges, notably impaired wound healing in the context of cisplatin (DDP) resistance. This study investigates the role of miR-200b in OC, emphasizing its impact on wound healing processes through DNMT3A/TGF-ß1 pathway. The primary aim was to explore how miR-200b regulates autophagy and its consequential effects on wound healing in OC, alongside its influence on cisplatin resistance. Utilizing DDP-sensitive (A2780) and resistant (A2780/DDP) OC cell lines, along with human fibroblast cultures, the study employed an array of in vitro techniques. These included cell transfection with miR-200b mimic or inhibitor, chromatin immunoprecipitation (ChIP), dual-luciferase reporter (DLR) assays, quantitative PCR, Western blotting, MTT and particularly, wound healing assays. The research highlighted the role of miR-200b in wound healing within OC. Inhibition of miR-200b in A2780 cells and its mimic in A2780/DDP cells affected cell viability, indicating the link with DDP resistance. Crucially, miR-200b mimic significantly delayed fibroblast-mediated wound closure in assays, underscoring its impact on wound healing. Bioinformatics analysis and subsequent DLR assays confirmed miR-200b's interaction with DNMT3A, affecting TGF-ß1 expression, the key factor in wound repair. Further, ChIP, quantitative PCR and Western blot analyses validated the interaction and expression changes in DNMT3A and TGF-ß1. The study demonstrated that miR-200b played a pivotal role in OC by modulating autophagy, which in turn significantly affected wound healing through the DNMT3A/TGF-ß1 pathway.

Improving optical coherence of light-emitting diodes by surface plasmons via shallow-etched conic pit array.

We propose the coupling of multiple quantum wells and surface plasmons can improve coherence of light emitted from LED wafers, as evidenced herein by a shallow-etched conic pit array with evaporated Ag (V-Ag) on a GaN-based LED wafer. The improvement in spatial coherence is critically verified by angle-resolved spectra. The temporal coherence length of the V-Ag wafer is 1.4 times larger than that of the plain wafer. The coherence-enhanced wafer achieves anisotropic and deflective emission in micro area and at far field by diffraction. This research provides a novel perspective on research of plasmonic LEDs and a new straightforward architecture to acquire partially coherent light from LEDs.

Automatic assessment of divergent thinking in Chinese language with TransDis: A transformer-based language model approach.

Language models have been increasingly popular for automatic creativity assessment, generating semantic distances to objectively measure the quality of creative ideas. However, there is currently a lack of an automatic assessment system for evaluating creative ideas in the Chinese language. To address this gap, we developed TransDis, a scoring system using transformer-based language models, capable of providing valid originality (novelty) and flexibility (variety) scores for Alternative Uses Task (AUT) responses in Chinese. Study 1 demonstrated that the latent model-rated originality factor, comprised of three transformer-based models, strongly predicted human originality ratings, and the model-rated flexibility strongly correlated with human flexibility ratings as well. Criterion validity analyses indicated that model-rated originality and flexibility positively correlated to other creativity measures, demonstrating similar validity to human ratings. Study 2 and 3 showed that TransDis effectively distinguished participants instructed to provide creative vs. common uses (Study 2) and participants instructed to generate ideas in a flexible vs. persistent way (Study 3). Our findings suggest that TransDis can be a reliable and low-cost tool for measuring idea originality and flexibility in Chinese language, potentially paving the way for automatic creativity assessment in other languages. We offer an open platform to compute originality and flexibility for AUT responses in Chinese and over 50 other languages ( https://osf.io/59jv2/ ).

Approaches of laparoscopic anatomical liver resection of segment 8 for hepatocellular carcinoma: a retrospective cohort study of short-term results at multiple centers in China.

BACKGROUND: Laparoscopic anatomical liver resection of segment 8 (LALR-S8) remains a challenge for anatomical laparoscopic segmentectomy. Most current reports on LALR-S8 are case series using one surgical approach, and there is a lack of multicenter data on identifying intersegmental planes using different approaches. In this study, the authors aimed to elucidate the short-term results of three different approaches for LALR-S8 for hepatocellular carcinoma (HCC), focusing on intersegmental plane determination, and to reflect on current practice regarding different approaches at multiple centers in China. MATERIALS AND METHODS: The clinical cohort data of 122 patients who underwent LALR-S8 for HCC at seven leading centers in China were retrospectively analyzed. The surgical procedures of all approaches were summarized and standardized according to the method of the Glissonean pedicle of segment 8 identification. The postoperative short-term outcomes and oncological results of the three approaches were evaluated and compared. RESULTS: Three approaches were used: laparoscopic ultrasonography-guided indocyanine green fluorescent positive staining approach (11/122, 9.02%), hepatic vein-guided approach (99/122, 81.15%), and Glissonean indocyanine green fluorescent negative staining approach (12/122, 9.83%). Seven (5.73%) patients experienced complications according to the Clavien-Dindo classification, and the rate of grade ≥IIIa complications was 2.46%. The R0 resection rates among the groups (margin >1 mm) and the margin width showed no statistical difference. CONCLUSION: LALR-S8 is safe and feasible for treating HCC under standardized surgical techniques and appropriate surgical approaches. The three reported approaches had comparable short-term oncological outcomes, while the hepatic vein-guided approach was most commonly used.

Physics-Based Differentiable Rendering for Efficient and Plausible Fluid Modeling from Monocular Video.

Realistic fluid models play an important role in computer graphics applications. However, efficiently reconstructing volumetric fluid flows from monocular videos remains challenging. In this work, we present a novel approach for reconstructing 3D flows from monocular inputs through a physics-based differentiable renderer coupled with joint density and velocity estimation. Our primary contributions include the proposed efficient differentiable rendering framework and improved coupled density and velocity estimation strategy. Rather than relying on automatic differentiation, we derive the differential form of the radiance transfer equation under single scattering. This allows the direct computation of the radiance gradient with respect to density, yielding higher efficiency compared to prior works. To improve temporal coherence in the reconstructed flows, subsequent fluid densities are estimated via a coupled strategy that enables smooth and realistic fluid motions suitable for applications that require high efficiency. Experiments on synthetic and real-world data demonstrated our method's capacity to reconstruct plausible volumetric flows with smooth dynamics efficiently. Comparisons to prior work on fluid motion reconstruction from monocular video revealed over 50-170x speedups across multiple resolutions.

Safety and efficacy of postoperative adjuvant therapy with atezolizumab and bevacizumab after radical resection of hepatocellular carcinoma.

BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.

Application of a hybrid GEM-CMB model for source apportionment of PAHs in soil of complex industrial zone.

Accurate source apportionment is essential for preventing the contamination of pervasive industrial zones. However, a limitation of traditional receptor models is their negligence of transmission loss, which consequently reduces their accuracy. Herein, chemical mass balance (CMB) and generic environmental model (GEM) was fused into a new method, which was employed to determine the traceability of polycyclic aromatic hydrocarbons (PAHs) in a complex zone containing three coking plants, two steel plants, and one energy plant. Five categories of fingerprints comprising various compounds were established for the six plant sources where seven PAHs with low-high rings were screened as the best. Considering volatilization, dry deposition, and advective and dispersive transport, the GEM model generated 232 "compartments" in multimedia to capture subtle variations of PAHs during transmission. More than 90 % of the transmission of the seven PAHs varied between 0.4 % and 6.0 %. Over pure CMB model, acceptable results and best-fit results improved by 1.6-44.4 % and 0.3-80.8 % in the GEM-CMB model. Additionally, the coking, steel, and energy industries accounted for 36.4-56.1 %, 25.6-41.7 %, and 18.3-23.6 % of PAHs sources at four receptor points, respectively. Furthermore, quantifying contaminant loss rendered the traceability results more realistic, judged by distances and discharge capacities. Accordingly, these outcomes can help in precisely determining soil contamination.

Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified. Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury. Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry. The pathology associated with the dysregulated lipids was examined. Results: Lipidomics analyses identified cardiolipins (CL) and sphingolipids (SL), including ceramides (CER), glycosphingolipids, sphingosines, and sphingomyelins, as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury. CER were increased in normal livers with I/R injury, and the I/R-induced increase of CER was further augmented in NASH livers. Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury, including serine palmitoyltransferase 3 (Sptlc3), ceramide synthase 2 (Cers2), neutral sphingomyelinase 2 (Smpd3), and glucosylceramidase beta 2 (Gba2) that produced CER, and alkaline ceramidase 2 (Acer2), alkaline ceramidase 3 (Acer3), sphingosine kinase 1 (Sphk1), sphingosine-1-phosphate lyase (Sgpl1), and sphingosine-1-phosphate phosphatase 1 (Sgpp1) that catalyzed the degradation of CER. CL were not affected by I/R challenge in normal livers, but CL was dramatically reduced in NASH livers with I/R injury. Consistently, metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury, including cardiolipin synthase (Crls1) and tafazzin (Taz). Notably, the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers, which were possibly mediated by the reduction of CL and accumulation of CER. Conclusions: The I/R-induced dysregulation of CL and SL were critically rewired by NASH, which might potentially mediate the aggressive I/R injury in NASH livers.

Electronic Properties of Vertically Stacked h-BN/B1-xAlxN Heterojunction on Si(100).

Hexagonal boron nitride (h-BN) exhibits a dangling bond-free layered structure and ultrawide band gap, which is apt to integrate with other semiconductors to form a heterojunction. Particularly, heterojunction structure is the main impetus for h-BN to broaden the horizon on deep ultraviolet optoelectronic and photovoltaic applications. Here, a series of h-BN/B1-xAlxN heterojunctions with different Al components were fabricated by radio frequency (RF) magnetron sputtering. The performance of h-BN/B1-xAlxN heterojunction was measured via I-V characteristic representation. The sample of h-BN/B0.89Al0.11N heterojunction was the best one due to the high lattice matching. Moreover, a type-II (staggered) band alignment was formed in this heterojunction which was elucidated by X-ray photoelectron spectroscopy (XPS). The calculated valence band offset (VBO) and conduction band offset (CBO) of h-BN/B0.89Al0.11N are 1.20 and 1.14 eV, respectively. The electronic properties and formation mechanism of h-BN/B0.89Al0.11N heterojunction were further studied by density functional theory (DFT) calculation. The existence of a built-in field (Ein) was confirmed, and the Ein direction was from the BAlN side to h-BN side. The staggered band alignment was further verified in this heterojunction, and an Al-N covalent bond existed at the interface from calculated results. This work paves a pathway to construct an ultrawide band gap heterojunction for the next-generated photovoltaic application.

Integrative epigenetic analysis reveals AP-1 promotes activation of tumor-infiltrating regulatory T cells in HCC.

Regulatory T (Treg) cells that infiltrate human tumors exhibit stronger immunosuppressive activity compared to peripheral blood Treg cells (PBTRs), thus hindering the induction of effective antitumor immunity. Previous transcriptome studies have identified a set of genes that are conserved in tumor-infiltrating Treg cells (TITRs). However, epigenetic profiles of TITRs have not yet been completely deciphered. Here, we employed ATAC-seq and CUT&Tag assays to integrate transcriptome profiles and identify functional regulatory elements in TITRs. We observed a global difference in chromatin accessibility and enhancer landscapes between TITRs and PBTRs. We identified two types of active enhancer formation in TITRs. The H3K4me1-predetermined enhancers are poised to be activated in response to tumor microenvironmental stimuli. We found that AP-1 family motifs are enriched at the enhancer regions of TITRs. Finally, we validated that c-Jun binds at regulatory regions to regulate signature genes of TITRs and AP-1 is required for Treg cells activation in vitro. High c-Jun expression is correlated with poor survival in human HCC. Overall, our results provide insights into the mechanism of AP-1-mediated activation of TITRs and can hopefully be used to develop new therapeutic strategies targeting TITRs in liver cancer treatment.

HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway.

BACKGROUND: Hepatic inflammation is a common initiator of liver diseases and considered as the primary driver of hepatocellular carcinoma (HCC). However, the precise mechanism of inflammation-induced HCC development and immune evasion remains elusive and requires extensive investigation. This study sought to identify the new target that is involved in inflammation-related liver tumorigenesis. METHODS: RNA-sequencing (RNA-seq) analysis was performed to identify the differential gene expression signature in primary human hepatocytes treated with or without inflammatory stimulus. A giant E3 ubiquitin protein ligase, HECT domain and RCC1-like domain 2 (HERC2), was identified in the analysis. Prognostic performance in the TCGA validation dataset was illustrated by Kaplan-Meier plot. The functional role of HERC2 in HCC progression was determined by knocking out and over-expressing HERC2 in various HCC cells. The precise molecular mechanism and signaling pathway networks associated with HERC2 in HCC stemness and immune evasion were determined by quantitative real-time PCR, immunofluorescence, western blot, and transcriptomic profiling analyses. To investigate the role of HERC2 in the etiology of HCC in vivo, we applied the chemical carcinogen diethylnitrosamine (DEN) to hepatocyte-specific HERC2-knockout mice. Additionally, the orthotopic transplantation mouse model of HCC was established to determine the effect of HERC2 during HCC development. RESULTS: We found that increased HERC2 expression was correlated with poor prognosis in HCC patients. HERC2 enhanced the stemness and PD-L1-mediated immune evasion of HCC cells, which is associated with the activation of signal transducer and activator of transcription 3 (STAT3) pathway during the inflammation-cancer transition. Mechanically, HERC2 coupled with the endoplasmic reticulum (ER)-resident protein tyrosine phosphatase 1B (PTP1B) and limited PTP1B translocation from ER to ER-plasma membrane junction, which ameliorated the inhibitory role of PTP1B in Janus kinase 2 (JAK2) phosphorylation. Furthermore, HERC2 knockout in hepatocytes limited hepatic PD-L1 expression and ameliorated HCC progression in DEN-induced mouse liver carcinogenesis. In contrast, HERC2 overexpression promoted tumor development and progression in the orthotopic transplantation HCC model. CONCLUSION: Our data identified HERC2 functions as a previously unknown modulator of the JAK2/STAT3 pathway, thereby promoting inflammation-induced stemness and immune evasion in HCC.

A Day/Night Leader-Following Method Based on Adaptive Federated Filter for Quadruped Robots.

The quadruped robots have superior adaptability to complex terrains, compared with tracked and wheeled robots. Therefore, leader-following can help quadruped robots accomplish long-distance transportation tasks. However, long-term following has to face the change of day and night as well as the presence of interference. To solve this problem, we present a day/night leader-following method for quadruped robots toward robustness and fault-tolerant person following in complex environments. In this approach, we construct an Adaptive Federated Filter algorithm framework, which fuses the visual leader-following method and the LiDAR detection algorithm based on reflective intensity. Moreover, the framework uses the Kalman filter and adaptively adjusts the information sharing factor according to the light condition. In particular, the framework uses fault detection and multisensors information to stably achieve day/night leader-following. The approach is experimentally verified on the quadruped robot SDU-150 (Shandong University, Shandong, China). Extensive experiments reveal that robots can identify leaders stably and effectively indoors and outdoors with illumination variations and unknown interference day and night.

Dynamics of microbial communities during inulin fermentation associated with the temporal response in SCFA production.

The ecology driving the remodeling of gut microbial consortia with dietary fiber intervention remains incomplete. We investigated the short-term dynamics of the gut microbiota and metabolic function during inulin fermentation with distinct microbiota from two swine breeds using an in vitro fermentation model. Different gut microbiota at a transient temporal time displayed a similar response to inulin intervention such as the similar fermentation stage and a rapid response followed by gradual stabilization of microbial diversity. Inulin-induced bacterial succession and individual metabolic change were determined by the original microbial compositions, in particular the α-diversity. Levels of short-chain fatty acids (SCFAs) were predictable with the key bacteria by the regression model, especially butyrate was associated with the abundance and ecological interactions of Lactobacillus delbrueckii, Bifidobacterium thermophilum and Megasphaera elsdenii. This study emphasizes the importance of complex ecology to understand fiber-induced microbiome and metabolic changes, thus providing a reference for predictable dietary responses.

Insights into Chlorobenzene Catalytic Oxidation over Noble Metal Loading {001}-TiO2: The Role of NaBH4 and Subnanometer Ru Undergoing Stable Ru0↔Ru4+ Circulation.

Catalytic combustion of ubiquitous chlorinated volatile organic compounds (CVOCs) encounters bottlenecks regarding catalyst deactivation by chlorine poisoning and generation of toxic polychlorinated byproducts. Herein, Ru, Pd, and Rh were loaded on {001}-TiO2 for thermal catalytic oxidation of chlorobenzene (CB), with Ru/{001}-TiO2 representing superior reactivity, CO2 selectivity, and stability in the 1000 min on-stream test. Interestingly, both acid sites and reactive active oxygen species (ROS) were remarkably promoted via adding NaBH4. But merely enhancing these active sites of the catalyst in CVOC treatment is insufficient. Continuous deep oxidation of CB with effective Cl desorption is also a core issue successfully tackled through the steady Ru0↔Ru4+ circulation. This circulation was facilitated by the observed higher subnanometer Ru dispersion on {001}-TiO2 than the other two noble metals that was supported by single atom stability DFT calculation. Nearly 88 degradation products in off-gas were detected, with Ru/{001}-TiO2 producing the lowest polychlorinated benzene byproducts. An effective and sustainable CB degradation mechanism boosted by the cooperation of NaBH4 enhanced active sites and Ru circulation was proposed accordingly. Insights gained from this study open a new avenue to the rational design of promising catalysts for the treatment of CVOCs.

PM2.5-mediated photochemical reaction of typical toluene in real air matrix with identification of products by isotopic tracing and FT-ICR MS.

The sight into photoconversion of toluene, a ubiquitous typical pollutant, attentively by the involvement of PM2.5 in the real air environment is crucial for controlling haze pollution. Compared with the large-size PM2.5 on normal day (PM2.5-ND), the PM2.5 on haze day (PM2.5-HD) formed of small particle agglomerates featured greater oxidation capability, evidenced by the valence distribution of sulfur species. Notably, PM2.5-HD had abundant O2-• and •OH and participated in the photochemical reaction of toluene, giving it a greater toluene conversion with a first-order kinetic rate constant of 0.4 d-1 on haze day than on normal day (0.2 d-1). During the toluene photoconversion, isotopic labelling traced small molecules including benzene and newfound pentane, ethylbenzene, 1,3,8-p-menthatriene and 4-methyl-1-pentanone benzene that could be formed by methyl breakage, ring opening, fragmentation reforming and addition reaction of toluene. Given ADMET properties, 1,3,8-p-menthatriene was assigned high priority since it had poor metabolism, low excretion and severe toxicity, while benzene and 4-methyl-1-pentanone benzene should also be noticeable. FT-ICR MS results indicated that toluene could create multiple macromolecular products that are more sensitive to SOA generation in haze air matrix with broader carbon number and O/C, more oxygenated substitution with CHO/CHON occupying by 81.4%, lower DBEaverage at 4.66 and higher OSC‾ at -1.60 than normal air matrix. Accordingly, a photochemical reaction mechanism for toluene in real air atmosphere was proposed. The stronger oxidation property of PM2.5 not only facilitated toluene to generate small molecules but also boosted the conversion of intermediates to oxygenated macromolecular products, contributing to the formation of SOA.

Characterization of somatic mutations and pathway alterations during hepatocellular carcinoma vascular invasion using next-generation sequencing.

Background: Vascular invasion is an independent risk factors for recurrence and poor prognosis in patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms of HCC vascular invasion are largely unknown. Deciphering the molecular changes associated with the vascular invasion process will aid in the identification of therapeutic targets and treatment for patients with HCC. Methods: DNA was extracted from tumor specimens and blood samples collected from 50 patients with HCC. Next-generation sequencing (NGS) was performed to detect HCC gene variants. Bioinformatics methods were used to comprehensively analyze the three sets of sequencing data grouped by vascular invasion, including differences in tumor mutation burden (TMB), mutation characteristics, and alterations in signaling pathways. Results: Bioinformatics analysis detected a total of 762 single nucleotide variants (SNVs). The TMB was not significantly different between patients with macrovascular invasion, microvascular invasion (MVI), or avascular invasion. Ten genes related to prognosis or recurrence, and one oncogene related to vascular invasion were screened. Compared with the avascular invasion cluster, the variant genes in the macrovascular and MVI clusters were mainly enriched in the thyroid hormone signaling pathway. In addition, macrovascular invasion variant genes were also enriched in the insulin signaling pathway and the Fanconi anemia pathway. Conclusions: Somatic mutations and pathway changes associated with vascular invasion in HCC were identified. The discovery of the molecular drivers of vascular invasion in HCC provides novel insights that can help guide further patient diagnosis and personalized therapy.