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Abstract Suppression of Tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor/ Toll-like receptor superfamily, and its specific ligand is Interleukin-33 (IL-33). IL-33/ ST2 signaling has been implicated in numerous inflammatory and allergic diseases, as well as in promoting malignant behavior of tumor cells and angiogenesis. However, the precise role of ST2 in gastric cancer angiogenesis remains incompletely elucidated. We observed a significant correlation between high expression of ST2 in gastric cancer tissues and poor prognosis, along with various clinicopathological features. In vitro experiments demonstrated that the IL-33/ ST2 axis activates the PI3K/AKT/NF-κB signaling pathway through TRAF6, thereby promoting VEGFA-mediated tumor angiogenesis; meanwhile sST2 acts as a decoy receptor to regulate the IL-33/ST2L axis. Consistent findings were also observed in subcutaneous xenograft tumor models in nude mice. Furthermore, we investigated the molecular mechanism by which IL-33 promotes ST2L expression in GC cells via upregulation of transcription factors YY1 and GATA2 through intracellular signaling pathways.

Abstract Due to rapid advancements in deep learning techniques, the demand for large-volume high-quality datasets grows significantly in chemical research. We developed a quantum-chemistry database that includes 443,106 small organic molecules with sizes up to 10 heavy atoms including C, N, O, and F. Ground-state geometry optimizations and frequency calculations of all compounds were performed at the B3LYP/6-31G* level with the BJD3 dispersion correction, while the excited-state single-point calculations were conducted at the ωB97X-D/6-31G* level. Totally twenty-seven molecular properties, such as geometric, thermodynamic, electronic and energetic properties, were gathered from these calculations. Meanwhile, we also established a comprehensive protocol for the construction of a high-volume quantum-chemistry dataset. Our QCDGE (Quantum Chemistry Dataset with Ground- and Excited-State Properties) dataset contains a substantial volume of data, exhibits high chemical diversity, and most importantly includes excited-state information. This dataset, along with its construction protocol, is expected to have a significant impact on the broad applications of machine learning studies across different fields of chemistry, especially in the area of excited-state research.

Acoustic cavitation plays a critical role in various biomedical applications. However, uncontrolled cavitation can lead to undesired damage to healthy tissues. Therefore, real-time monitoring and quantitative evaluation of cavitation dynamics is essential for understanding underlying mechanisms and optimizing ultrasound treatment efficiency and safety. The current research addressed the limitations of traditionally used cavitation detection methods by developing introduced an adaptive time-division multiplexing passive cavitation imaging (PCI) system integrated into a commercial diagnostic ultrasound platform. This new method combined real-time cavitation monitoring with B-mode imaging, allowing for simultaneous visualization of treatment progress and 2D quantitative evaluation of cavitation dosage within targeted area. An improved delay-and-sum (DAS) algorithm, optimized with a minimum variance (MV) beamformer, is utilized to minimize the side lobe effect and improve the axial resolution typically associated with PCI. In additional to visualize and quantitatively assess the cavitation activities generated under varied acoustic pressures and microbubble concentrations, this system was specifically applied to perform 2D cavitation evaluation for ultrasound thrombolysis mediated by different solutions, e.g., saline, nanodiamond (ND) and nitrogen-annealed nanodiamond (N-AND). This research aims to bridge the gap between laboratory-based research systems and real-time spatiotemporal cavitation evaluation demands in practical uses. Results indicate that this improved 2D cavitation monitoring and evaluation system could offer a useful tool for comprehensive evaluating cavitation-mediated effects (e.g., ultrasound thrombolysis), providing valuable insights into in-depth understanding of cavitation mechanisms and optimization of cavitation applications.

IntroductionHyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear.Methods> Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated.ResultsAbnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep.DiscussionThe relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

For any $ R > 0 $, infinitely many nonradial singular solutions can be constructed for the following equation: $ \begin{equation} -\Delta u = e^u \;\;\; \mbox{in}\; B_R \backslash \{0\} , \;\;\;\;\;\;(0.1)\end{equation} $ where $ B_R = \{x \in \mathbb{R}^N \; (N \geq 3): \; |x| < R\} $. To construct nonradial singular solutions, we need to consider asymptotic expansion at the isolated singular point $ x = 0 $ of a prescribed solution of (0.1). Then, nonradial singular solutions of (0.1) can be constructed by using the asymptotic expansion and introducing suitable weighted Hölder spaces.

In order to improve the seismic resistance of infrastructure and reduce the seismic disaster risk of important infrastructure, based on the results of earthquake disaster risk census in Zhejiang Province, comprehensively considering the construction age, site type, fortification standards, construction area, building status of sports venues, etc., the investigation and assessment of potential earthquake hazards of gymnasiums in Zhejiang Province was carried out. The main influencing factors of the earthquake disaster risk level of gymnasium were discussed, and then suggestions were put forward for gymnasiums with different risk hazard levels, including local reinforcement, special assessment, popular science among the people, etc. The assessment of earthquake disaster risk of sports venues is conducive to further understanding the potential earthquake hazard of gymnasiums and the real seismic fortification capacity of gymnasiums, and at the same time it can provide experience for effectively promoting the application of risk survey results in Zhejiang Province.

Alterations in the tumor microenvironment are closely associated with the metabolic phenotype of tumor cells. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth and metastasis. Existing studies have suggested that lactate produced by tumor cells can activate CAFs, yet the precise underlying mechanisms remain largely unexplored. In this study, we initially identified that lactate derived from lung cancer cells can promote nuclear translocation of NUSAP1, subsequently leading to the recruitment of the transcriptional complex JUNB-FRA1-FRA2 near the DESMIN promoter and facilitating DESMIN transcriptional activation, thereby promoting CAFs' activation. Moreover, DESMIN-positive CAFs, in turn, secrete IL-8, which recruits TAMs or promotes M2 polarization of macrophages, further contributing to the alterations in the tumor microenvironment and facilitating lung cancer progression. Furthermore, we observed that the use of IL-8 receptor antagonists, SB225002, or Navarixin, significantly reduced TAM infiltration and enhanced the therapeutic efficacy of anti-PD-1 or anti-PD-L1 treatment. This finding indicates that inhibiting IL-8R activity can attenuate the impact of CAFs on the tumor microenvironment, thus restraining the progression of lung cancer.

Abstract The ever-growing quantities of persistent Polytetrafluoroethylene (PTFE) wastes, along with consequential ecological and human health concerns, stimulate the need for alternative PTFE disposal method. The central research challenge lies in elucidating the decomposition mechanism of PTFE during high-temperature waste treatment. Here, we propose the PTFE microscopic thermal decomposition pathways by integrating plasma gasification experiments with multi-scale simulations strategies. Molecular dynamic simulations reveal a pyrolysis—oxidation & chain-shortening—deep defluorination (POCD) degradation pathway in an oxygen atmosphere, and an F abstraction—hydrolysis—deep defluorination (FHD) pathway in a steam atmosphere. Density functional theory computations demonstrate the vital roles of 1O2 and ·H radicals in the scission of PTFE carbon skeleton, validating the proposed pathways. Experimental results confirm the simulation results and show that up to 80.12% of gaseous fluorine can be recovered through plasma gasification within 5 min, under the optimized operating conditions determined through response surface methodology.

Abstract Background Lactylation, a novel contributor to post-translational protein modifications, exhibits dysregulation across various tumors. Nevertheless, its intricate involvement in colorectal carcinoma, particularly for non-histone lactylation and its intersection with metabolism and immune evasion, remains enigmatic. Methods Employing immunohistochemistry on tissue microarray with clinical information and immunofluorescence on colorectal cell lines, we investigated the presence of global lactylation and its association with development and progression in colorectal cancer as well as its functional location. Leveraging the AUCell algorithm alongside correlation analysis in single-cell RNA sequencing data, as well as cox-regression and lasso-regression analysis in TCGA dataset and confirmed in GEO dataset, we identified a 23-gene signature predicting colorectal cancer prognosis. Subsequently, we analyzed the associations between the lactylation related gene risk and clinical characteristics, mutation landscapes, biological functions, immune cell infiltration, immunotherapy responses, and drug sensitivity. Core genes were further explored for deep biological insights through bioinformatics and in vitro experiments. Results Our study innovatively reveals a significant elevation of global lactylation in colorectal cancer, particularly in malignant tumors, confirming it as an independent prognostic factor for CRC. Through a comprehensive analysis integrating tumor tissue arrays, TCGA dataset, GEO dataset, combining in silico investigations and in vitro experiments, we identified a 23-gene Lactylation-Related Gene risk model capable of predicting the prognosis of colorectal cancer patients. Noteworthy variations were observed in clinical characteristics, biological functions, immune cell infiltration, immune checkpoint expression, immunotherapy responses and drug sensitivity among distinct risk groups. Conclusions The Lactylation-Related Gene risk model exhibits significant potential for improving the management of colorectal cancer patients and enhancing therapeutic outcomes, particularly at the intersection of metabolism and immune evasion. This finding underscores the clinical relevance of global lactylation in CRC and lays the groundwork for mechanism investigation and targeted therapeutic strategies given the high lactate concentration in CRC.

Abstract Spark is a widely studied plasma source for active species production; however, it experiences unstable transitions (e.g. to a thermal arc) at high frequencies or long pulse durations. In this study, the sparks generated in a pulse train were studied and modulated based on a physics‐corrected deep learning method. Our results show that a highly repeatable and stable spark plasma source can be achieved by automatically adjusting the voltage amplitude according to the discharge frequency in a high‐frequency pulse train within the time scale of the fluid response. The influences of the electron number density increasing mode and modulated driven voltage profiles on the energy efficiencies were also studied.

Traditional femtosecond laser modeling relies on the iterative solution of the Nonlinear Schrödinger Equation (NLSE) using the Split-Step Fourier Method (SSFM). However, SSFM’s high computational complexity leads to significant time consumption, particularly in automatic control and system optimization, thus limiting control model responsiveness. Recent studies have suggested using neural networks to simulate fiber dynamics, offering faster computation and lower costs. In this study, we introduce a novel fiber propagation method utilizing the DeepONet architecture for the first time. By separately managing fiber parameters and input–output pulses in the branch and trunk networks, this method can simulate various fiber configurations with high accuracy and without altering the architecture. Additionally, while SSFM generation time increases linearly with fiber length, the GPU-accelerated AI generation time remains consistent at around 0.0014 s, regardless of length. Notably, in high-order soliton (HOS) compression over a 12 m distance, the AI method is approximately 56,865 times faster than SSFM.

Objective To examine the prevalence and influencing factors of vaccine hesitation among adult citizens during a major public health emergency for promoting vaccination in China. MethodsUsing random sampling and a self-designed questionnaire on vaccine hesitation and its associates, we conducted an online survey among 4 325 citizens aged 18 – 59 years in five provincial level administrative divisions (Guangdong, Hubei, Hebei, and Heilongjiang province and Beijing municipality) across China during February – March, 2021, a period of with a major public health emergency. ResultsOf the 4 169 eligible respondents, 1 479 (35.5%) reported vaccine hesitation. The results of unconditional multivariate logistic regression analysis showed that the respondents with following characteristics were more likely to have vaccine hesitation: being female, suffering from chronic diseases, with poor self-rated health, with high perceived risk of the epidemic, and being highly concerned about the epidemic-related information; while, the respondents ever having influenza vaccination, reporting a high community responsibility, with relatives/friends/colleagues being vaccinated with coronoavirus disease vaccine, and with the cognition on the efficacy and the safety of the coronavirus disease vaccine were less likely to have the vaccine hesitation. ConclusionVaccine hesitation was prevalent among adult citizens in China during a major public health emergency and the hesitation was associated with gender, self-assessed health, chronic disease condition, influenza vaccination, sense of social responsibility, perceived risk of the epidemic, concern about the epidemic, coronavirus disease vaccination of relatives/friends/colleagues, and the cognition of the efficacy and the safety of the coronavirus disease vaccine.

Abstract Non-Hermitian systems are known for their intriguing topological properties, which underpin various exotic physical phenomena. Exceptional points, in particular, play a pivotal role in fine-tuning these systems for optimal device functionality and material characteristics. These points can give rise to exceptional surfaces with embedded lower-dimensional non-isolated singularities. Here we introduce a topological classification for non-defective intersection lines of exceptional surfaces, where exceptional surfaces intersect transversally. We achieve this classification by constructing a quotient space of an order-parameter space under equivalence relations of eigenstates. We unveil that the fundamental group of these gapless structures is a non-Abelian group on three generators. This classification not only reveals a unique form of non-Hermitian gapless phases featuring a chain of non-defective intersection lines but also predicts the unexpected existence of topological edge states in one-dimensional lattice models protected by the intersection singularities. Our classification opens avenues for realizing robust topological phases.

Background Insomnia disorder (ID) is one of the most common mental disorders. Research on ID focuses on exploring its mechanism of disease, novel treatments and treatment outcome prediction. An emerging technique in this field is the use of electroencephalography (EEG) microstates, which offer a new method of EEG feature extraction that incorporates information from both temporal and spatial dimensions.Aims To explore the electrophysiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) for ID treatment and use baseline microstate metrics for the prediction of its efficacy.Methods This study included 60 patients with ID and 40 age-matched and gender-matched good sleep controls (GSC). Their resting-state EEG microstates were analysed, and the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were collected to assess sleep quality. The 60 patients with ID were equally divided into active and sham groups to receive rTMS for 20 days to test whether rTMS had a moderating effect on abnormal microstates in patients with ID. Furthermore, in an independent group of 90 patients with ID who received rTMS treatment, patients were divided into optimal and suboptimal groups based on their median PSQI reduction rate. Baseline EEG microstates were used to build a machine-learning predictive model for the effects of rTMS treatment.Results The class D microstate was less frequent and contribute in patients with ID, and these abnormalities were associated with sleep onset latency as measured by PSG. Additionally, the abnormalities were partially reversed to the levels observed in the GSC group following rTMS treatment. The baseline microstate characteristics could predict the therapeutic effect of ID after 20 days of rTMS, with an accuracy of 80.13%.Conclusions Our study highlights the value of EEG microstates as functional biomarkers of ID and provides a new perspective for studying the neurophysiological mechanisms of ID. In addition, we predicted the therapeutic effect of rTMS on ID based on the baseline microstates of patients with ID. This finding carries great practical significance for the selection of therapeutic options for patients with ID.

Abstract Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons.

Head-to-tail macrocyclization of proteins and peptides can increase their structural stability, however, potential polymerization can lead to reduced yields. Here, the authors report the engineering of self-cyclizing ‘autocyclase’ proteins to generate macrocyclic peptides and proteins with favorable reaction kinetics for suppressing polymerization.

Abstract Background Facility cultivation is widely applied to meet the increasing demand for high yield and quality, with light intensity and light quality being major limiting factors. However, how changes in the light environment affect development and quality are unclear in garlic. When garlic seedlings are grown, they can also be exposed to blanching culture conditions of darkness or low-light intensity to ameliorate their appearance and modify their bioactive compounds and flavor. Results In this study, we determined the quality and transcriptomes of 14-day-old garlic and blanched garlic seedlings (green seedlings and blanched seedlings) to explore the mechanisms by which seedlings integrate light signals. The findings revealed that blanched garlic seedlings were taller and heavier in fresh weight compared to green garlic seedlings. In addition, the contents of allicin, cellulose, and soluble sugars were higher in the green seedlings. We also identified 3,872 differentially expressed genes between green and blanched garlic seedlings. The Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment for plant-pathogen interactions, phytohormone signaling, mitogen-activated protein kinase signaling, and other metabolic processes. In functional annotations, pathways related to the growth and formation of the main compounds included phytohormone signaling, cell wall metabolism, allicin biosynthesis, secondary metabolism and MAPK signaling. Accordingly, we identified multiple types of transcription factor genes involved in plant-pathogen interactions, plant phytohormone signaling, and biosynthesis of secondary metabolites among the differentially expressed genes between green and blanched garlic seedlings. Conclusions Blanching culture is one facility cultivation mode that promotes chlorophyll degradation, thus changing the outward appearance of crops, and improves their flavor. The large number of DEGs identified confirmed the difference of the regulatory machinery under two culture system. This study increases our understanding of the regulatory network integrating light and darkness signals in garlic seedlings and provides a useful resource for the genetic manipulation and cultivation of blanched garlic seedlings.

In order to simulate the effects of reconstructing misconnected nodes in the drainage system and quantify sewage routing paths during the rainy season, we have selected a specific region in Fangchenggang City as our study area. All misconnected nodes have been divided into 10 areas based on their respective blocks and streets. COD, NH4+-N, TN, and TP are chosen as evaluation indexes, and we have utilized SWMM for modelling purposes. The results indicate that nodes located upstream within the drainage watershed tend to have a broader influence scope, with a maximum pollutant load reduction rate of 8.6%. However, it is worth noting that the normalization effect could worsen if a reconstruction scheme contains more nodes. Our methodology for calculating the pollutant load reduction rate of pipelines presents a novel approach for quantifying pollutant reduction effects, sewage flow paths, and geographical visualization. This approach has the potential to address the knowledge gap in exploring pollutant transfer routes.

Abstract Although the effects of electron‐deficient group substitution on isoindigo on the corresponding conjugated polymers are extensively studied, the modification of isoindigo core with electron‐rich groups has not been investigated. It is envisioned that the introduction of the methoxy group on isoindigo will not only tune the highest occupied molecular orbital (HOMO) energy level of the corresponding polymers but also introduce O···S “conformation lock” to increase the coplanarity of the polymers, which should facilitate hole transport. Herein, the syntheses of two methoxylated isoindigos and the investigations on the charge transport behaviors of their copolymers with bisthiophene (2T) and bisthiazole (2Tz) are reported. It is found that the substitution positions have a drastic influence on the UV–vis absorption and electrochemical properties for both monomers and polymers. Theoretical calculations and single crystal structure analysis confirm the existence of O···S “conformation lock”, however, both methoxy substitutions also change the aggregation behaviors of the corresponding polymers to a mixed face‐on/edge‐on orientation which has an adverse effect for charge transport. Among the four polymers, the polymer of 5,5'‐methoxylated isoindigo and 2T exhibit the best hole mobility of 1.9 × 10−1 cm2 V−1 s−1.

Metabolic disorders represent a major therapeutic challenge to public health worldwide due to their dramatically increasing prevalence. Acupuncture is widely used as adjuvant therapy for multiple metabolic diseases. However, detailed biological interpretation of the acupuncture stimulations is still limited. The gut and the liver are intrinsically connected and related to metabolic function. Microbial metabolites might affect the gut-liver axis through multiple mechanisms. Liver metabolomics and 16S rRNA sequencing were used to explore the specific mechanism of electroacupuncture in treating ZDF rats in this study. Electroacupuncture effectively improved glycolipid metabolism disorders of the ZDF rats. Histopathology confirmed that electroacupuncture improved diffuse hepatic steatosis and hepatocyte vacuolation, and promoted glycogen accumulation in the liver. The treatment significantly improved microbial diversity and richness and upregulated beneficial bacteria that maintain intestinal epithelial homeostasis and decreased bacteria with detrimental metabolic features on host metabolism. Liver metabolomics showed that the main effects of electroacupuncture include reducing the carbon flow and intermediate products in the TCA cycle, regulating the metabolism of various amino acids, and inhibiting hepatic glucose output and de novo lipogenesis. The gut-liver axis correlation analysis showed a strong correlation between the liver metabolites and the gut microbiota, especially allantoin and Adlercreutzia. Electroacupuncture treatment can improve abnormal energy metabolism by reducing oxidative stress, ectopic fat deposition, and altering metabolic fluxes. Our results will help us to further understand the specific mechanism of electroacupuncture in the treatment of metabolic diseases.

Chemical kinetic studies of the β-scission reaction class of hydroperoxyl alkyl hydroperoxyl radicals (•P(OOH)2) from normal-alkyl cyclohexanes are carried out systematically through high-level ab initio calculations. Geometry optimizations and frequency calculations for all species involved in the reactions are performed at the B3LYP/CBSB7 level of theory. Electronic single-point energy calculations are calculated at the CBS-QB3 level of theory. Rate constants for the reactions of β-scission, in the temperature range of 500–1500 K and the pressure range of 0.01–100 atm, are calculated using transition state theory (TST) and Rice-Ramsberger-Kassel-Marcus/Master-Equation (RRKM/ME) theory taking asymmetric Eckart tunneling corrections and the one-dimensional hindered rotor approximation into consideration. The rate rules are obtained by averaging the rate constants of the representative reactions of this class. These rate rules can greatly assist in constructing more accurate low-temperature combustion mechanisms for normal-alkyl cyclohexanes.

The role of the Ca2+-permeable ion channel TRPC5 in regulating vasocontraction in obesity is poorly understood. Here, we investigated whether TRPC5 contributes to vascular dysfunction in obesity by promoting endothelium-dependent contraction via activation of cytosolic phospholipase A2 (cPLA2) in the aortic endothelial cells of obese mice. Acetylcholine-induced endothelium-dependent relaxation and contraction in the aorta were measured using wire myography. PLA2 activity was measured by the fluorogenic PLA2 substrate Bis-BODIPY™ FL C11-PC. The intracellular Ca2+ level in response to acetylcholine was measured by Fluo-4 fluorescence. Endothelium-derived contracting factors were assessed by enzyme immunoassay. Diet-induced obesity (DIO) attenuated endothelium-dependent vasodilation, enhanced endothelium-dependent contraction (EDC), and increased the expression of TRPC5 in the mouse aorta. Activation of TRPC5 promoted EDC in the wild-type mouse aorta, whereas pharmacological inhibition and genetic knockout of TRPC5 decreased EDC in the DIO mouse aorta. Moreover, cPLA2 phosphorylation and activity were higher in aortic endothelial cells from DIO mice, and this was attenuated by inhibition and knockout of TRPC5. Cyclooxygenase 2 (COX-2) expression was increased in DIO mouse endothelium and was decreased by a TRPC5 inhibitor and knockout of TRPC5. Release of prostaglandins F2α (PGF2α) and E2 (PGE2) was involved in TRPC5-regulated EDC in DIO mice. This study demonstrated that TRPC5 contributes to endothelial and vascular dysfunction and is involved in EDC through activation of cPLA2 and enhanced COX-2-PGF2α/PGE2 levels in DIO mice.

The concerted elimination reaction class of peroxyl-hydroperoxyl alkyl radicals (•OOQOOH) plays a crucial role in the low-temperature combustion of normal-alkyl cyclohexanes. The generation of the relatively unreactive HO2 radicals in this reaction is one of the factors leading to the negative temperature coefficient (NTC) behavior, which hinders the low-temperature oxidation of normal-alkyl cyclohexanes. In this study, 44 reactions are selected and divided into 4 different subclasses according to the nature of the carbon atom where the H atom is eliminated and the reaction center position. Utilizing the CBS-QB3 method, we compute the energy barriers for the concerted elimination reactions of peroxyl-hydroperoxyl alkyl radicals. Following this, we assess both the high-pressure limit and pressure-dependent rate constants for all reactions by applying TST and RRKM/ME theory. These calculations allow for the development of rate rules, which come to fruition through an averaging process involving the rate constants of representative reactions within each subclass. Our work provides accurate rate constants and rate rules for this reaction class, which can aid in constructing more accurate combustion mechanisms for normal-alkyl cyclohexanes.

The global network threat is becoming more and more serious, and network security vulnerability management has become one of the critical areas in the national information security emergency system construction. To guide the third-party sharing platforms regarding network security vulnerability management, this work constructs a signal game model comprising third-party vulnerability sharing platforms and software vendors for vulnerability collaborative disclosures. In addition, we analyze the game strategy selection and its influencing factors. The results show that there are two perfect Bayesian equilibria, including separation equilibrium and mixed equilibrium, due to the incomplete lines of information disclosure. The equilibrium state is mainly based on the compression time of the protection period and the existence ratio of the software vendors who develop the patches in the market. This work puts forward some suggestions in terms of the protection period, reputation loss, and relevant laws and regulations.

PurposeIn our study, we aim to analyze the impact of clinicopathological factors on the recommendation of extended endocrine therapy (EET) in patients with ER+ breast cancer and to retrospectively validate the value of CTS5 in EET decision making.Patients and methodsThe retrospective analysis was performed in patients with ER+ breast cancer who have finished 4.5–5 years of adjuvant endocrine therapy and undergone MDT discussion from October 2017 to November 2019. Multivariate logistic regression was used to identify the independent factors for treatment recommendation. CTS5 was calculated for retrospective validation of the EET decision making.ResultsTwo hundred thirty-five patients were received; 4.5–5 years of adjuvant endocrine therapy were included in the study. Multivariate analysis suggested that age (OR 0.460, 95% CI 0.219–0.965, p = 0.04), pN (OR 39.350, 95% CI 9.831–157.341, P < 0.001), and receipt of chemotherapy (OR 3.478, 95% CI 1.336–9.055, p = 0.011) were independent predictors for the recommendation of EET. In the previously selective estrogen receptor modulator (SERM)–treated subgroup, pN and receipt of chemotherapy were independent predictors for the recommendation of EET. In the previously AI-treated subgroup, age, pN, and receipt of chemotherapy were independent predictors. Adverse events did not affect the recommendation in patients previously treated with adjuvant endocrine treatment nor in the previously SERM or AI-treated subgroups. CTS5 (OR 21.887, 95% CI 2.846–168.309, p = 0.003) remained an independent predictor for the recommendation of EET.ConclusionsOur study indicated that age, lymph nodal status, and receipt of chemotherapy were independent predictors for the recommendation of EET. The application of the CTS5 on EET decision making might be valuable among ER+ breast cancer patients.

Abstract Background TREM2 is a microglial receptor genetically linked to the risk for Alzheimer’s disease (AD). The cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2) have emerged as a valuable biomarker for the disease progression in AD and higher CSF levels of sTREM2 are linked to slower cognitive decline. Increasing sTREM2 in mouse models of amyloidosis reduces amyloid-related pathology through modulating microglial functions, suggesting a beneficial role of sTREM2 in microglia biology and AD pathology. Methods In the current study, we performed serial C- and N-terminal truncations of sTREM2 protein to define the minimal sequence requirement for sTREM2 function. We initially assessed the impacts of sTREM2 mutants on microglial functions by measuring cell viability and inflammatory responses. The binding of the sTREM2 mutants to oligomeric Aβ was determined by solid-phase protein binding assay and dot blot assay. We further evaluated the impacts of sTREM2 mutants on amyloid-related pathology by direct stereotaxic injection of sTREM2 proteins into the brain of 5xFAD mice. Results We found that both sTREM2 fragments 41–81 and 51–81 enhance cell viability and inflammatory responses in primary microglia. However, the fragment 51–81 exhibited impaired affinity to oligomeric Aβ. When administrated to the 5xFAD mice brain, the sTREM2 fragment 41–81, but not 51–81, increased the number of plaque-associated microglia and reduced the plaque deposition. Interestingly, the fragment 41–81 was more efficient than the physiological form of sTREM2 in ameliorating Aβ-related pathology. Conclusions Our results indicate that the interaction of sTREM2 truncated variants with Aβ is essential for enhancing microglial recruitment to the vicinity of an amyloid plaque and reducing the plaque load. Importantly, we identified a 41-amino acid sequence of sTREM2 that is sufficient for modulating microglial functions and more potent than the full-length sTREM2 in reducing the plaque load and the plaque-associated neurotoxicity. Taken together, our data provide more insights into the mechanisms underlying sTREM2 function and the minimal active sTREM2 sequence represents a promising candidate for AD therapy.

BackgroundMena, a cytoskeletal regulatory protein, is involved in actin-based regulation of cell motility and adhesion, and contributes to tumor invasion and metastasis. However, the role of Mena in oral squamous cell carcinoma remains unclear. This is the first research focusing on the prognostic value of Mena in OSCC. In this study, we aimed to investigate the correlation between Mena expression and clinicopathological significance, as well as prognostic value in OSCC.MethodsMena gene expression profiles of OSCC and normal tissues were collected from Oncomine, TCGA, and GEO databases. Biological function was analyzed through GO, KEGG and GSEA enrichment. Further, the expression level of Mena and tumor-related markers in 151 OSCC specimens was examined by IHC staining based on tissue microarray. Kaplan-Meier analysis was used to assess the prognostic performance of Mena in OSCC.ResultMena was generally upregulation in various malignancies, especially OSCC. The functional analyses indicated that Mena was involved in the assembly and regulation of actin, cell movement, and EMT. IHC staining revealed that high expression of Mena in OSCC was correlated with Lymphatic metastasis, TNM stage, E-cadherin, Vimentin, and MMP-2, but insignificantly Ki67. Kaplan-Meier analysis demonstrated that elevated expression of Mena was significantly associated with poor overall survival and disease-free survival of OSCC patients.ConclusionMena could be a novel biomarker for predicting the prognosis of OSCC patients, which supports a theoretical basis for developing molecular target therapy.

ObjectiveTo investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis.MethodsLevels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis.ResultsLevels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β (TGF-β) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis.ConclusionsmiRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.

It is notorious that cancer cells alter their metabolism to adjust to harsh environments of hypoxia and nutritional starvation. Metabolic reprogramming most often occurs in the tumor microenvironment (TME). TME is defined as the cellular environment in which the tumor resides. This includes surrounding blood vessels, fibroblasts, immune cells, signaling molecules and the extracellular matrix (ECM). It is increasingly recognized that cancer cells, fibroblasts and immune cells within TME can regulate tumor progression through metabolic reprogramming. As the most significant proportion of cells among all the stromal cells that constitute TME, cancer-associated fibroblasts (CAFs) are closely associated with tumorigenesis and progression. Multitudinous studies have shown that CAFs participate in and promote tumor metabolic reprogramming and exert regulatory effects via the dysregulation of metabolic pathways. Previous studies have demonstrated that curbing the substance exchange between CAFs and tumor cells can dramatically restrain tumor growth. Emerging studies suggest that CAFs within the TME have emerged as important determinants of metabolic reprogramming. Metabolic reprogramming also occurs in the metabolic pattern of immune cells. In the meanwhile, immune cell phenotype and functions are metabolically regulated. Notably, immune cell functions influenced by metabolic programs may ultimately lead to alterations in tumor immunity. Despite the fact that multiple previous researches have been devoted to studying the interplays between different cells in the tumor microenvironment, the complicated relationship between CAFs and immune cells and implications of metabolic reprogramming remains unknown and requires further investigation. In this review, we discuss our current comprehension of metabolic reprogramming of CAFs and immune cells (mainly glucose, amino acid, and lipid metabolism) and crosstalk between them that induces immune responses, and we also highlight their contributions to tumorigenesis and progression. Furthermore, we underscore potential therapeutic opportunities arising from metabolism dysregulation and metabolic crosstalk, focusing on strategies targeting CAFs and immune cell metabolic crosstalk in cancer immunotherapy.

This paper investigates the transient aerodynamic interference of rotors imposed on fuselage for a quadcopter through Computational Fluid Dynamics (CFD) simulations. The numerical study of transient effects due to rotor rotation is enabled by sliding mesh which defines the rotation domains encompassing rotor blades. The results show that the interference effects of rotor change the aerodynamic forces of the fuselage, causing about 67% in-crease in lift, 13% increase in drag, and 90% increase in pitching up moment on average. The variations of fuselage lift are associated with the pressure distribution changes due to rotors rotation, the high-pressure areas and low-pressure areas over the rotor projects on the arms of the quadcopter causing periodical abrupt changes on the lift, drag and pitching moment.

Background Transient receptor potential canonical (TRPC) channels play a role in angiogenesis. However, the involvement of TRPC1 in myocardial infarction (MI) remains unclear. The present study was aimed at investigating whether TRPC1 can improve the recovery of cardiac function via prompting angiogenesis following MI. Methods and Results In vitro, coronary artery endothelial cells from floxed TRPC1 mice and endothelial cell‐specific TRPC1 channel knockout mice were cultured to access EC angiogenesis. Both EC tube formation and migration were significantly suppressed in mouse coronary artery endothelial cells from endothelial cell‐specific TRPC1 channel knockout mice. In vivo, coronary artery endothelial cells from floxed TRPC1 and endothelial cell‐specific TRPC1 channel knockout mice were subjected to MI, then echocardiography, triphenyltetrazolium chloride staining and immunofluorescence were performed to assess cardiac repair on day 28. Endothelial cell‐specific TRPC1 channel knockout mice had higher ejection fraction change, larger myocardial infarct size, and reduced capillary density in the infarct area compared with coronary artery endothelial cells from floxed TRPC1 mice. Furthermore, we found underlying regulation by HIF‐1α (hypoxic inducible factor‐1α) and MEK‐ERK (mitogen‐activated protein kinase/extracellular signal‐regulated kinase) that could be the mechanism for the angiogenetic action of TRPC1. Significantly, treatment with dimethyloxaloylglycine, an activator of HIF‐1α, induced cardiac improvement via the HIF‐1α‐TRPC1‐MEK/ERK pathway in MI mice. Conclusions Our study demonstrated TRPC1 improves cardiac function after MI by increasing angiogenesis via the upstream regulator HIF‐1α and downstream MEK/ERK, and dimethyloxaloylglycine treatment has protective effect on MI through the HIF‐1α‐TRPC1‐MEK/ERK pathway.

Enzyme catalysis has attracted increasing attention for application in the synthesis of polymer hydrogel due to the eco-friendly process and the devisable catalytic reaction. Moreover, bottom-up approaches combining enzyme catalysts and molecular self-assembly have been explored for synthesizing hydrogel with complex architectures. An enzyme widely distributed in nature, transglutaminase (TGase) has been confirmed to catalyze the formation of isopeptide bonds between proteins, which can effectively improve the gelation of proteins. In this mini-review, TGase-catalyzed synthesis of polymer hydrogels, including fibrin hydrogels, polyethylene glycol hydrogels, soy protein hydrogels, collagen hydrogels, gelatin hydrogels and hyaluronan hydrogels, has been reviewed in detail. The catalytic process and gel formation mechanism by TGase have also been considered. Furthermore, future perspectives and challenges in the preparation of polymer hydrogels by TGase are also highlighted.

Large-scale high-voltage trip-offs (HVTOs) of wind farms are serious incidents afflicting power systems that can lead to voltage instability, power deficiency, and frequency fluctuation. In order to reduce the influence of HVTOs, it is necessary to efficiently identify the fault source after an HVTO at a wind farm. A fault source identification method for wind farm HVTOs is proposed in this work. First, the fault tree analysis (FTA) method is used to summarize the causal and logical relationships among the different factors that lead to HVTOs at wind farms. An index system is constructed according to simulations of wind farm HVTOs under multiple scenarios. Second, a set of feature indices are selected from the original index system as key criteria for wind farm HVTOs based on the symmetrical uncertainty of mutual information and the maximum relevance and minimum redundancy (SU-MRMR) method. Finally, the particle swarm optimization (PSO) method is effectively utilized in the parameter optimization of support vector machine (SVM) method, and the optimized SVM with good performance is further employed for fault source identification based on the feature indices. Both single fault source and compound fault source are identified in an actual power system, and the proposed method is verified as a reliable solution for complex fault source identification for wind farm HVTOs based on the statistical identification accuracy.

Fusidic acid (FA) is a natural tetracyclic triterpene isolated from fungi, which is clinically used for systemic and local staphylococcal infections, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections. FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial, antimalarial, antituberculosis, anticancer, tumor multidrug resistance reversal, anti-inflammation, antifungal, and antiviral activity in vivo and in vitro. The semisynthesis, structural modification and biological activities of FA derivatives have been extensively studied in recent years. This review summarized the biological activities and structure–activity relationship (SAR) of FA in the last two decades. This summary can prove useful information for drug exploration of FA derivatives.

BackgroundComprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited.MethodsWe evaluated the relations of the 21-gene recurrence risk score (RS) and the expression of cancer-related genes with metabolic factors and biomarkers of insulin and the insulin-like growth factor (IGF) axis, and examined the interactions between the 21-gene RS and these metabolic profiles on breast cancer recurrence in Chinese women with HR-positive, HER2-negative early-stage breast cancer.ResultsThe 21-gene RS was inversely associated with body mass index ([BMI]β: −0.178 kg/m2; P=0.040), the homeostasis model assessment of insulin resistance index ([HOMA-IR] β: −0.031; P=0.042), insulin (β: −0.036 uIU/ml; P=0.009), and C-peptide (β: −0.021 ug/L; P=0.014) and was positively associated with high-density lipoprotein cholesterol (β: 0.025 mmol/L; P=0.004), which were driven by the relation patterns between specific cancer-related genes and these metabolic profiles. Each 10-unit increase in the 21-gene RS was associated with 28% (95% CI: 5–47%) higher risk of breast cancer recurrence; this association was also observed in patients with favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk).ConclusionsThe 21-gene RS was related to favorable metabolic profiles including lower BMI, HOMA-IR, insulin, and C-peptide, and higher HDL in Chinese breast cancer patients, and its prognostic impact on breast cancer recurrence was more likely to present among patients with relatively favorable metabolic profiles.

Next-generation sequencing (NGS) is an emerging method with the potential of pan-pathogen screening. This study described a case of eosinophilic meningitis (EoM) with enzyme-linked immunosorbent assay (ELISA)-negative results for Angiostrongylus cantonensis (A. cantonensis), Trichinella spiralis and Paragonimus westermani and a positive identification of A. cantonensis by NGS in the cerebrospinal fluid.

TREM2 is a genetic risk factor for Alzheimer’s disease, and soluble TREM2 (sTREM2) in the CSF correlates with AD progression. Here the authors study the role of sTREM2 in a mouse model of Alzheimer’s disease, and find it reduces amyloid accumulation and increases the numbers of plaque-associated microglia which correlates with improved behavioural function in the mice.

In recent years, due to adverse geological conditions, intense human engineering activities, and extreme weather conditions, catastrophic landslides have frequently occurred in southwest China, causing severe loss of life and property. Identifying the kinematic features of potential landslides can effectively support landslide hazard prevention. This study proposes a remote sensing identification method for rotational, planar traction, and planar thrust slides based on geomorphic features as well as vertical and slope-oriented deformation rates. Rotational landslides are characterized by similar vertical and horizontal deformation rates, with vertical deformation mainly occurring at the head and gradually decreasing along the slope, while horizontal deformation mainly occurs at the foot and gradually increases along the slope. As for the planar slide, the dominant deformation is in the horizontal direction. It is further classified into the planar traction and planar thrust types according to the driving position. The vertical deformation of planar traction slides is concentrated at the foot, while the vertical deformation of planar thrust slides is concentrated at the head of the landslide. We identified 1 rotational landslide, 10 planar traction landslides and 10 planar thrust landslides in the basalt weathering crust area of Guizhou. Field investigations of three landslides verified the method’s accuracy. Combining two-dimensional rainfall and time-series deformations, we found that there is a significant positive correlation between landslide deformation acceleration and precipitation. The landslide kinematic identification method proposed in this paper overcomes the shortcomings of the inability to accurately characterize landslide motion by line-of-sight displacement and realizes the non-contact identification of active landslide motion patterns, which is an essential reference value for geological disaster prevention and control in the study area.

At the neighborhood scale, recognizing urban community green space (UCGS) is important for residential living condition assessment and urban planning. However, current studies have embodied two key issues. Firstly, existing studies have focused on large geographic scales, mixing urban and rural areas, neglecting the accuracy of green space contours at fine geographic scales. Secondly, the green spaces covered by shadows often suffer misclassification. To address these issues, we created a neighborhood-scale urban community green space (UCGS) dataset and proposed a segmentation decoder for HRNet backbone with two auxiliary decoders. Our proposed model adds two additional branches to the low-resolution representations to improve their discriminative ability, thus enhancing the overall performance when the high- and low-resolution representations are fused. To evaluate the performance of the model, we tested it on a dataset that includes satellite images of Shanghai, China. The model outperformed the other nine models in UCGS extraction, with a precision of 83.01, recall of 85.69, IoU of 72.91, F1-score of 84.33, and OA of 89.31. Our model also improved the integrity of the identification of shaded green spaces over HRNetV2. The proposed method could offer a useful tool for efficient UCGS detection and mapping in urban planning.

Background: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear.Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment.Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29–0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27–1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18–0.89), were premenopausal (HR, 0.34; 95% CI, 0.12–0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17–0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25–0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26–0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence.Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors.

Oxidation reactions play a critical role in processes involving energy utilization, chemical conversion, and pollutant elimination. However, due to its spin-forbidden nature, the reaction of molecular dioxygen (O2) with a substrate is difficult under mild conditions. Herein, we describe a system that activates O2 via the direct modulation of its spin state by mechanical energy-induced triboelectric corona plasma, enabling the CO oxidation reaction under normal temperature and pressure. Under optimized reaction conditions, the activity was 7.2 μmol h−1, and the energy consumption per mole CO was 4.2 MJ. The results of kinetic isotope effect, colorimetry, and density functional theory calculation studies demonstrated that electrons generated in the triboelectric plasma were directly injected into the antibonding orbital of O2 to form highly reactive negative ions O2−, which effectively promoted the rate-limiting step of O2 dissociation. The barrier of the reaction of O2− ions and CO molecular was 3.4 eV lower than that of O2 and CO molecular. This work provides an effective strategy for using renewable and green mechanical energy to realize spin-forbidden reactions of small molecules.

The surface discharge is the elementary process in a broad range of low temperature plasma applications. Variation of voltage profiles with different time scales leads to the redistribution of deposited energy as well as electro-hydrodynamic forces of surface discharges, while the mechanism and scaling law is still unknown. On the basis of theoretical and numerical analysis, we show that a secondary surface ionization wave forms during the voltage rising slope when electron density decreases to a critical level while the voltage is still rising. A characteristic map of energy and electro-hydrodynamics force in time scales between 1 ns and 0.1 s at atmospheric pressure is proposed, opening the door towards the target-directed design of surface discharges.

The original version of this Article omitted the following from the end of the Acknowledgements: ‘X.C. also received funding from the Shenzhen Basic Research Program JCYJ20170818140904167.’ This has now been corrected in both the PDF and HTML versions of the Article.