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Many studies have indicated an alarming prevalence of anxiety among Chinese adolescents, highlighting the critical need for prevention protocols. DNA-V (Discoverer, Noticer, Advisor-Values model) is an adapted version of Acceptance and Commitment Therapy designed to prevent mental health problems in adolescents. This study investigated the effects and underlying mechanisms of DNA-V. The DNA-V prevention program was culturally adapted and optimized in both content and form specifically for Chinese adolescents, with the aim of reducing anxiety levels. A total of 139 participants (59 females) from six eighth-grade classes at an average middle school in Beijing were randomly assigned to one of three groups consisting of the DNA-V face-to-face group (two classes), the DNA-V web-based group (two classes), or the active control group (two classes). Adolescents' anxiety and cognitive fusion were measured before (Time 1), immediately after (Time 2), and 2 months after (Time 3) the program using the Chinese Secondary School Students Anxiety Scale (CSSSAS) and Cognitive Fusion Questionnaire (CFQ). Results showed that in the DNA-V face-to-face group, the anxiety score at Time 3 was significantly lower than the scores at Time 1 (p < .001, Cohen's drm = 0.56) and Time 2 (p = .043, Cohen's drm = 0.24). The cognitive fusion score at Time 3 was significantly lower than the scores at Time 1 (p = .001, Cohen's drm = 0.51) and Time 2 (p = .003, Cohen's drm = 0.37). The results of the study suggest that the DNA-V prevention program could serve as an effective tool for reducing anxiety in adolescents.

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Exosomes, nanosized extracellular vesicles containing biomolecular cargo, are increasingly recognized as promising noninvasive biomarkers for cancer diagnosis, particularly for their role in carrying tumor-specific molecular information. Traditional methods for exosome detection face challenges such as complexity, time consumption, and the need for sophisticated equipment. This study addresses these challenges by introducing a novel droplet microfluidic platform integrated with a surface-enhanced Raman spectroscopy (SERS)-based aptasensor for the rapid and sensitive detection of HER2-positive exosomes from breast cancer cells. Our approach utilized an on-chip salt-induced gold nanoparticles (GNPs) aggregation process in the presence of HER2 aptamers and HER2-positive exosomes, enhancing the hot spot-based SERS signal amplification. This platform achieved a limit of detection of 4.5 log10 particles/mL with a sample-to-result time of 5 min per sample. Moreover, this platform has been successfully applied for HER2 status testing in clinical samples to distinguish HER2-positive breast cancer patients from HER2-negative breast cancer patients. High sensitivity, specificity, and the potential for high-throughput screening of specific tumor exosomes make this SERS-based droplet system a potential liquid biopsy technology for early cancer diagnosis.

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Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H2 evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.

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One of the primary challenges for immune checkpoint blockade (ICB)-based therapy is the limited infiltration of T lymphocytes (T cells) into tumors, often referred to as immunologically "cold" tumors. A promising strategy to enhance the anti-tumor efficacy of ICB is to increase antigen exposure, thereby enhancing T cell activation and converting "cold" tumors into "hot" ones. Herein, we present an innovative all-in-one therapeutic nanoplatform to realize local mild photothermal- and photodynamic-triggered antigen exposure, thereby improving the anti-tumor efficacy of ICB. This nanoplatform involves conjugating programmed death-ligand 1 antibody (aPD-L1) with gadolinium-doped near-infrared (NIR)-emitting carbon dots (aPD-L1@GdCDs), which displays negligible cytotoxicity in the absence of light. But under controlled NIR laser irradiation, the GdCDs produce combined photothermal and photodynamic effects. This not only results in tumor ablation but also induces immunogenic cell death (ICD), facilitating enhanced infiltration of CD8+ T cells in the tumor area. Importantly, the combination of aPD-L1 with photothermal and photodynamic therapies via aPD-L1@GdCDs significantly boosts CD8+ T cell infiltration, reduces tumor size, and improves anti-metastasis effects compared to either GdCDs-based phototherapy or aPD-L1 alone. In addition, the whole treatment process can be monitored by multi-modal fluorescence/photoacoustic/magnetic resonance imaging (FLI/PAI/MRI). Our study highlights a promising nanoplatform for cancer diagnosis and therapy, as well as paves the way to promote the efficacy of ICB therapy through mild photothermal- and photodynamic-triggered immunotherapy.

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Bone marrow endothelial progenitor cells (BM EPCs) are crucial in supporting haematopoietic regeneration, while the BM EPCs of haematological patients with chemotherapy-induced thrombocytopenia (CIT) are unavoidably damaged. Therefore, the present study aimed to examine the effect of thrombopoietin (TPO) on the recovery of BM EPCs of CIT patients and to identify the underlying mechanisms. The cell functions were determined by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake and fluorescein isothiocyanate (FITC)-labeled Ulex europaeus agglutinin-I (FITC-UEA-I) binding assay, as well as proliferation, migration and tube formation experiments. Endothelial cells were transfected with METTL16 lentivirus, followed by methylated RNA immunoprecipitation sequencing. Zebrafish with vascular defect was used as the in vivo model. TPO significantly improved the quantity and functions of BM EPCs from CIT patients in vitro and restored the subintestinal vein area of zebrafish with vascular defect in vivo. Mechanically, TPO enhanced the BM EPC functions through Akt signal mediated by METTL16, which was downregulated in BM EPCs of CIT patients and involved in the regulation of endothelial functions. The present study demonstrates that TPO improves the recovery of BM EPCs from CIT patients with haematological malignancies via METTL16/Akt signalling, which provides new insights into the role of TPO in treating CIT in addition to direct megakaryopoiesis.

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Fluorogenic RNAs such as the Mango aptamers are uniquely powerful tools for imaging RNA. A central challenge has been to develop brighter, more specific, and higher affinity aptamer-ligand systems for cellular imaging. Here, we report an ultra-bright fluorophore for the Mango II system discovered using a structure-informed, fragment-based small molecule microarray approach. The new dye, Structure informed, Array-enabled LigAnD 1 (SALAD1) exhibits 3.5-fold brighter fluorescence than TO1-Biotin and subnanomolar aptamer affinity. Improved performance comes solely from alteration of dye-RNA interactions, without alteration of the chromophore itself. Multiple high-resolution structures reveal a unique and specific binding mode for the new dye resulting from improved pocket occupancy, a more defined binding pose, and a novel bonding interaction with potassium. The dye notably improves in-cell confocal RNA imaging. This work provides both introduces a new RNA-activated fluorophore and also a powerful demonstration of how to leverage fragment-based ligand discovery against RNA targets.

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This study reports a fluorescent nanoprobe operated in fluorescence turn-on mode for simultaneously sensing and imaging intracellular GSH and ATP. By using maleimide-derivatives as the ligand, the bimetallic nanoscale metal-organic framework (NMOF) Cu-Mi-UiO-66 has been synthesized for the first time using a straightforward one-step solvothermal approach, serving as a GSH recognition moiety. Subsequently, a Cy5-labeled ATP aptamer was assembled onto Cu-Mi-UiO-66 via strong coordination between phosphate and zirconium, π-π stacking and electrostatic adsorption to develop the dual-responsive fluorescence nanoprobe Cu-Mi-UiO-66/aptamer. Due to the photoinduced electron transfer (PET) effect between maleimide groups and the benzene ring of the ligand and the charge transfer between Cy5 and the Zr(IV)/Cu(II) bimetal center of the NMOF, the Cu-Mi-UiO-66/aptamer exhibits a fluorescence turn-off status. The Michael addition reaction between the thiol group of GSH and the maleimide on the NMOF skeleton results in turning on of the blue fluorescence of Cu-Mi-UiO-66. Meanwhile, upon specific interaction with ATP, the aptamer changes into internal loop structures and detaches from Cu-Mi-UiO-66, resulting in turning on of the red fluorescence of Cy5. The nanoprobe demonstrated an excellent sensing performance with a good linear range (GSH, 5.0-450.0 µM; ATP, 1.0-50.0 µM) and a low detection limit (GSH, 2.17 µM; ATP, 0.635 µM). More importantly, the Cu-Mi-UiO-66/aptamer exhibits good performance for tracing intracellular concentration variations of GSH and ATP in living HepG2 cells under different stimulations. This study highlights the potential of NMOFs for multiplexed analysis and provides a valuable tool for tumor microenvironment research and early cancer diagnosis.

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Hepatic ischemia-reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA-approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane-camouflaged liposomes. These hybrid nanovesicles (NVs), leveraging MSC-derived proteins, demonstrate efficient inflammatory chemotaxis, transendothelial migration, and drug-loading capacity. In a HIRI mouse model, the biomimetic NVs accumulated at liver injury sites entered hepatocytes, and significantly reduced liver damage and restore function using only one-tenth of the CsA dose typically required. Proteomic analysis verifies the protection mechanism, which includes reactive oxygen species inhibition, preservation of mitochondrial integrity, and reduced cellular apoptosis, suggesting potential for this biomimetic strategy in HIRI intervention.

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BACKGROUND: Blackberry seeds, as a by-product of processing, have potential bioactive substances and activities. A response surface method was used to determine the optimal conditions of blackberry seed extracts (BSEs) with high 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity by ultrasound-assisted extraction (UAE). The composition and antioxidant capacity of BSEs were further analyzed. RESULTS: The optimal conditions were material-to-liquid ratio of 0.07 g mL-1, ethanol concentration of 56%, extraction temperature of 39 °C and ultrasonic power of 260 W. Using these conditions, the extraction yield and total polysaccharide, phenolic and anthocyanin contents in BSEs were 0.062 g g-1 and 633.91, 36.21 and 3.07 mg g-1, respectively. The Fourier transform infrared spectra of BSEs exhibited characteristic peaks associated with polysaccharide absorption. The antioxidant capacity, DPPH and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, and ferric reducing antioxidant power of BSEs were 1533.19, 1021.93 and 1093.38 mmol Trolox equivalent g-1, respectively. The delphinidin-3-O-glucoside, paeoniflorin-3-O-glucoside and cyanidin-3-O-arabinoside contents in BSEs were 3.05,12.76 and 1895.90 ± 3.45 µg g-1. Five polyphenols including gallic acid, coumaric acid, ferulic acid, catechin and caffeic acid were identified and quantified in BSEs with its contents at 8850.43, 5053.26, 4984.65, 1846.91 and 192.40 µg g-1. CONCLUSION: These results provide a method for preparing BSE containing functional components such as polysaccharides, phenols and anthocyanins through UAE, and BSEs have potential application in food industries. © 2024 Society of Chemical Industry.

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Liquid biopsy is a non-invasive diagnostic method that can reduce the risk of complications and offers exceptional benefits in the dynamic monitoring and acquisition of heterogeneous cell population information. Optical nanomaterials with excellent light absorption, luminescence, and photoelectrochemical properties have accelerated the development of liquid biopsy technologies. Owing to the unique size effect of optical nanomaterials, their improved optical properties enable them to exhibit good sensitivity and specificity for mitigating signal interference from various molecules in body fluids. Nanomaterials with biocompatible and optical sensing properties play a crucial role in advancing the maturity and diversification of liquid biopsy technologies. This article offers a comprehensive review of recent advanced liquid biopsy technologies that utilize novel biocompatible optical nanomaterials, including fluorescence, colorimetric, photoelectrochemical, and Raman broad-spectrum-based biosensors. We focused on liquid biopsy for the most significant early biomarkers in clinical medicine, and specifically reviewed reports on the effectiveness of optical nanosensing technology in the detection of real patient samples, which may provide basic evidence for the transition of optical nanosensing technology from engineering design to clinical practice. Furthermore, we introduced the integration of optical nanosensing-based liquid biopsy with modern devices, such as smartphones, to demonstrate the potential of the technology in portable clinical diagnosis.

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Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.

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OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

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Monitoring T lymphocyte differentiation is essential for understanding T cell fate regulation and advancing adoptive T cell immunotherapy. However, current biomarker analysis methods necessitate cell lysis, leading to source depletion. Intracellular pH (pHi) can be affected by the presence of lactic acid (LA), a metabolic mediator of T cell activity such as glycolysis during T cell activation; therefore, it is a potentially a good biomarker of T cell state. In this work, a dual emitting enhancement-based nanoprobe, namely, AIEgen@F127-AptCD8, was developed to accurately detect the pHi of T cells to "read" the T cell differentiation process. The nanocore of this probe comprises a pair of AIE dyes, TPE-AMC (pH-sensitive moiety) and TPE-TCF, that form a donor-acceptor pair for sensitive detection of pHi by dual emitting enhancement analysis. The nanoprobe exhibits a distinctly sensitive narrow range of pHi values (from 6.0 to 7.4) that can precisely distinguish the differentiated lymphocytes from naïve ones based on their distinct pHi profiles. Activated CD8+ T cells demonstrate lower pHi (6.49 ± 0.09) than the naïve cells (7.26 ± 0.11); Jurkat cells exhibit lower pHi (6.43 ± 0.06) compared to that of nonactivated ones (7.29 ± 0.09) on 7 days post-activation. The glycolytic product profiles in T cells strongly correlate with their pHi profiles, ascertaining the reliability of probing pHi for predicting T cell states. The specificity and dynamic detection capabilities of this nanoprobe make it a promising tool for indirectly and noninvasively monitoring T cell activation and differentiation states.

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Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre- and early-symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early-onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with post-symptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over nine years. The most common adverse events (AEs) within two months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with post-symptomatic juvenile MLD.

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RNAs are increasingly considered valuable therapeutic targets, and the development of methods to identify and validate both RNA targets and ligands is more important than ever. Here, we utilized a bioinformatic approach to identify a hairpin-containing RNA G-quadruplex (rG4) in the 5' untranslated region (5' UTR) of DHX15 mRNA. By using a novel competitive small molecule microarray (SMM) approach, we identified a compound that specifically binds to the DHX15 rG4 (K D = 12.6 ± 1.0 µM). This rG4 directly impacts translation of a DHX15 reporter mRNA in vitro, and binding of our compound (F1) to the structure inhibits translation up to 57% (IC50 = 22.9 ± 3.8 µM). This methodology allowed us to identify and target the mRNA of a cancer-relevant helicase with no known inhibitors. Our target identification method and the novelty of our screening approach make our work informative for future development of novel small molecule cancer therapeutics for RNA targets.

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Retinitis pigmentosa is the main cause of inherited human blindness and is associated with dysfunctional photoreceptors (PRs). Compared with traditional methods, optoelectronic stimulation can better preserve the structural integrity and genetic content of the retina. However, enhancing the spatiotemporal accuracy of stimulation is challenging. Quantum dot-doped ZnIn2S4 microflowers (MF) are utilized to construct a biomimetic photoelectric interface with a 0D/3D heterostructure, aiming to restore the light response in PR-degenerative mice. The MF bio interface has dimensions similar to those of natural PRs and can be distributed within the curved spatial region of the retina, mimicking cellular dispersion. The soft 2D nano petals of the MF provide a large specific surface area for photoelectric activation and simulate the flexibility interfacing between cells. This bio interface can selectively restore the light responses of seven types of retina ganglion cells that encode brightness. The distribution of responsive cells forms a pattern similar to that of normal mice, which may reflect the generation of the initial "neural code" in the degenerative retina. Patch-clamp recordings indicate that the bio interface can induce spiking and postsynaptic currents at the single-neuron level. The results will shed light on the development of a potential bionic subretinal prosthetic toolkit for visual function restoration.

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PURPOSE: Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy. METHODS: HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2. RESULTS: PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model. CONCLUSION: Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

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Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.

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Cycloalkanes serve as an important class of chemical components in both fossil and alternative transportation fuels and have attracted considerable attention from the combustion community. Hydrogen abstractions from cycloalkanes by hydroxyl radicals initiate the fuel decomposition process and trigger off the subsequent chain reactions and thus play an important role in both combustion and atmospheric chemistry. The target of this study is to fill the vacancy in kinetics data toward the H-abstraction reactions by hydroxyl radical from three typical dimethylcyclohexane isomers through first-principles and direct dynamics. The rate constants involving 18 elementary reactions in total were accurately determined by the multipath canonical variational transition state theory with the multidimensional small-curvature correction for tunneling (MP-CVT/SCT), over a broad temperature range of 200-2000 K. The significant roles of multistructural torsional anharmonicity and recrossing effects were stressed per abstraction site, while the quantum tunneling effect was found to be slight at temperatures of interest in combustion. The discrepancies observed among different reaction systems at a similar abstraction site highlight the fuel molecular effects on site-specific rate constants. The comparison results of total rate constants given by different dynamics approaches prove the importance of considering the torsional anharmonicity, recrossing, and tunneling effects, and the robust feature of the simplified MS-CVT/SCT. The calculated total constants for dimethylcyclohexane isomers by OH are consistent with those measured for methylcyclohexane and 1,4-dimethylcyclohexane at low temperatures. The branching ratio analysis confirms the predominant role of the tertiary abstraction at low-to-intermediate temperatures and its growing competition with distinct secondary abstractions as temperature increases. The calculated rate constants were eventually fitted into the analytical expressions and incorporated into the kinetic models to learn about the influences on modeling performance.

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Polycystic ovary syndrome (PCOS) is a globally prevalent gynecological disorder among women of childbearing age. The present study aimed to investigate the role of tenascin C (TNC) in PCOS and its potential mechanisms. Fasting blood glucose and serum insulin, the homeostasis model assessment of insulin resistance and the serum hormone levels were determined in PCOS rats. In addition, H&E staining was used for assessing pathology. In addition, the effects of TNC on oxidative stress and inflammation response in PCOS rat and cell models was assessed. Furthermore, the roles of TNC on KGN cell proliferation and apoptosis were determined employing EdU assay and flow cytometry. TLR4/NF­κB pathway­related proteins were measured using western blotting, immunofluorescence and immunohistochemistry. It was found that the mRNA and protein expression was upregulated in PCOS rats and in KGN cells induced by dihydrotestosterone (DHT). Knockdown of TNC relieved the pathological characteristics and the endocrine abnormalities of PCOS rats. Knockdown of TNC inhibited ovarian cell apoptosis, oxidative stress and inflammation in PCOS rats. Knockdown of TNC reversed the DHT­induced reduction in cell proliferation and increase in apoptosis in KGN cells. Furthermore, knockdown of TNC alleviated oxidative stress and inflammatory responses induced by DHT in KGN cells. Additionally, knockdown of TNC inhibited the toll­like receptor 4 (TLR4)/NF­κB signaling pathway in PCOS rats and DHT­treated KGN cells. In conclusion, knockdown of TNC could ameliorate PCOS in both rats and a cell model by inhibiting cell apoptosis, oxidative stress and inflammation via the suppression of the TLR4/NF­κB signaling pathway.

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