Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2 /SRC pathway in vascular cognitive impairment mice.

AIM: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). METHODS: The active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y-maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme-linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2 , p-SRC, SRC, VEGFA, and inflammatory markers including IL-10, IL-1ß, TNF-α, and IL-6 were subsequently assessed. RESULTS: The VEGFR2 /SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO-induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL-1ß, IL-6, and TNF-α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) and blocked microglial M1-polarization by modulating the VEGFR2 /SRC signaling pathway. CONCLUSION: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2 /SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.

Proposals for the delineation of neck clinical target volume for definitive Radiation therapy in patients with oral/ oropharyngeal squamous cell cancer based on lymph node distribution.

PURPOSE/OBJECTIVE(S): To establish the distribution pattern of cervical lymph node metastasis (LNM) and propose optimized clinical target volume (CTV) boundaries specific to oral/ oropharyngeal squamous cell cancer (OSCC/OPSCC). MATERIALS/METHODS: 531 patients with pathologically confirmed OSCC/OPSCC were enrolled from January 2013 to June 2022. Patients were stratified into two groups based on the minimal distance from the lesion's edge to the body's midline: ≤1 cm or > 1 cm. The geometric center of cervical metastatic LN was marked on a template CT. LN distribution probability maps were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for CTV boundaries specific to OSCC/OPSCC. RESULTS: A total of 1962 positive LNs were enrolled. Compared with the > 1 cm group, the ≤ 1 cm group has following feature tendencies: male smokers, younger, median organs, large gross lesion, infiltrative growth pattern, contralateral LNM. The most frequently involved level of LNM was ipsilateral II, but ipsilateral Ib had the highest involvement rate in the > 1 cm OSCC group. In addition, tongue cancer had a higher incidence of LN extranodal extension (ENE), which mainly distributes in ipsilateral level II. The skip metastasis was prone to from level III to Vb (3.5 %) in LN(+)/ENE (-), and level Ib to VIa (3.7 %) in LN(+)/ENE (+). Accordingly, we proposed the following modifications: 1. only including lateral and posterior margin of submandibular gland within 5 mm; 2. retracting posterior boundary of level II to front edge of levator scapula muscle, and descending the upper boundary to transverse process of C2 vertebra only for OSCC; 3. including posterior third of thyroglossal muscle or anterior edge of sternocleidomastoid muscle; 4. sparing level Va in case of only level II involvement; 5. including upper area of the thyroid cartilage plate in case of level Ib LN(+)/ENE (+); 6. sparing level VIIa is considered. CONCLUSION: This is the first description of LN topographic spread patterns for OSCC/OPSCC. Modified CTV for prophylactic irradiation was proposed to spare the organs at risk and minimize adverse effects.

Monocyte to high-density lipoprotein ratio as an independent predictor of intracranial atherosclerotic stenosis-related emergency large vessel occlusion.

OBJECTIVE: To evaluate the correlation between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and intracranial atherosclerotic stenosis-related emergent large vessel occlusion (ICAS-ELVO) in acute ischemic stroke patients with endovascular thrombectomy. METHODS: Included in this study were 215 patients who underwent endovascular thrombectomy. They were randomly assigned to training and testing datasets. The patients in training dataset (n=128) were divided into ICAS group (n=65) and embolism group (n=63). MHR was compared between the two groups. According to the cut-off value, patients in testing dataset (n=87) were divided into low-MHR group (n=54) and high-MHR group (n=33). MHR was compared between the two groups. RESULTS: In training dataset, the proportion of male patients, diabetic patients and smokers in ICAS group was significantly higher than that in embolism group [(50 (76.9%) vs. 30 (47.6%), P=0.001; 29 (44.6%) vs. 14(22.2%), P=0.007; 37(56.9%) vs. 14 (22.2%), P=0.001; 37 (56.9%) vs. 14 (22.2%), P=0.001], while the mean age and the proportion of patients with coronary heart disease (CHD), stroke and atrial fibrillation were significantly lower [(64.74±9.13 vs. 71.38±13.34, P=0.001; 6 (9.2%) vs. 14 (22.2%), P=0.043; 12 (18.5%) vs. 22 (34.9%), P=0.035; 5 (7.7%)vs. 56 (88.9%), P<0.001)]. The laboratory test results showed that monocyte count was significantly higher and high-density lipoprotein level was significantly lower in ICAS group than those in embolism group (0.61±0.26 vs. 0.45±0.13, P=0.001; 1.17±0.28 vs. 1.37±0.27, P=0.001). MHR in ICAS group was significantly higher than that in embolism group (0.55±0.26 vs. 0.34±0.11, P=0.001). In training set, MHR was found to be an independent predictor for the occurrence of ICAS-ELVO with an adjusted OR of 2.39 (95%CI 1.29-4.48, P=0.006). ROC curve analysis showed that the area under the curve (AUC) of MHR was 0.8 (95% CI, 0.72-0.87, p < 0.001), with a sensitivity of 0.60 and a specificity of 0.873. The optimal cut-off value of the MHR level was 0.46. In testing dataset, the rate of ICAS-ELVO in higher quartile was significantly higher than that in the lower quartile (81.8% vs. 33.3%, P<0.001). Patients with a low MHR had a higher rate of cerebral hemorrhagic than those with a high MHR. CONCLUSION: MHR was associated with ICAS-ELVO in acute ischemic stroke patients with endovascular thrombectomy, and the higher level of MHR does benefit to differentiate ICAS from intracranial embolism, suggesting that MHR may prove to be an independent predictor for ICAS-ELVO.

Entangled dark state mediated by a dielectric cavity within epsilon-near-zero materials.

Two emitters can be entangled by manipulating them through optical fields within a photonic cavity. However, maintaining entanglement for a long time is challenging due to the decoherence of the entangled qubits, primarily caused by cavity loss and atomic decay. Here, we found the entangled dark state between two emitters mediated by a dielectric cavity within epsilon-near-zero (ENZ) materials, ensuring entanglement maintenance over an extended period. To obtain the entangled dark state, we derived an effective model with degenerate mode modulation. In the dielectric cavities within ENZ materials, the decay rate of emitters can be regarded as 0, which is the key to achieving the entangled dark state. Meanwhile, the dark state immune to cavity loss exists when two emitters are in symmetric positions in the dielectric cavity. Additionally, by adjusting the emitters to specific asymmetric positions, it is possible to achieve transient entanglement with higher concurrence. By overcoming the decoherence of the entangled qubits, this study demonstrates stable, long-term entanglement with ENZ materials, holding significant importance for applications such as nanodevice design for quantum communication and quantum information processing.

Correlations of 2 Novel Inflammation Indexes With the Risk for Early Neurological Deterioration in Acute Ischemic Stroke Patients After Intravenous Thrombolytic Therapy.

OBJECTIVES: Elevation of the systemic immune inflammation (SII) index and system inflammation response index (SIRI) is known to be associated with higher risk of stroke and all-cause death. However, no study has reported their correlation with early neurological deterioration (END) following recombinant tissue-type plasminogen activator (IV-rtPA) in acute ischemic stroke patients. The aim of this study was to explore the correlation of SII and SIRI with the risk of END after IV-rtPA. METHODS: Included in this study were 466 consecutive patients treated with IV-rtPA. SII and SIRI were calculated according to blood cell counts before IV-rtPA. Patients were divided into 3 groups based on trisectional quantiles according to SII and SIRI values. The risk of END was assessed by multivariate regression. The overall discriminative ability of SII and SIRI in predicting END was assessed by receiver operating characteristic curve analysis. RESULTS: Of the 466 included patients, 62 (13.3%) were identified as having END. Compared with the first tertile of SII, multivariable regression analysis demonstrated that patients were more likely to have END (odds ratio 2.54; 95% CI: 1.23-5.23) and poor outcome at 90 days (odds ratio 2.02; 95% CI: 1.06-3.86) in third tertile after adjustment for potential confounders. In addition, a cutoff value of 591.63 for SII was detected in predicting post-thrombolysis END with a sensitivity of 58.1% and a specificity of 64.6% (area under the curve 0.61; 95% CI: 0.54-0.69). CONCLUSIONS: Higher SII but not SIRI may prove to be a predictor for high risk of END and a poor functional outcome at 90 days after IV-rtPA.

Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients.

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.

Plant-derived monoterpene S-linalool and ß-ocimene generated by CsLIS and CsOCS-SCZ are key chemical cues for attracting parasitoid wasps for suppressing Ectropis obliqua infestation in Camellia sinensis L.

Insect-induced plant volatile organic compounds (VOCs) may function as either direct defence molecules to deter insects or indirect defence signals to attract the natural enemies of the invading insects. Tea (Camellia sinensis L.), an important leaf-based beverage crop, is mainly infested by Ectropis obliqua which causes the most serious damage. Here, we report a mechanistic investigation of tea plant-derived VOCs in an indirect defence mechanism against E. obliqua. Parasitoid wasp Parapanteles hyposidrae, a natural enemy of E. obliqua, showed strong electrophysiological response and selection behaviour towards S-linalool and ß-ocimene, two monoterpenes with elevated emission from E. obliqua-damaged tea plants. Larvae frass of E. obliqua, which also released S-linalool and ß-ocimene, was found to attract both mated female or male Pa. hyposidrae according to gas chromatography-electroantennogram detection and Y-tube olfactometer assays. In a field setting, both S-linalool and ß-ocimene were effective in recruiting both female and male Pa. hyposidrae wasps. To understand the molecular mechanism of monoterpenes-mediated indirect defence in tea plants, two novel monoterpene synthase genes, CsLIS and CsOCS-SCZ, involved in the biosynthesis of S-linalool or ß-ocimene, respectively, were identified and biochemically characterised. When the expression of these two genes in tea plants was inhibited by antisense oligodeoxynucleotide, both volatile emission and attraction of wasps were reduced. Furthermore, gene expression analysis suggested that the expression of CsLIS and CsOCS-SCZ is regulated by the jasmonic acid signalling pathway in the tea plant.

WLP3 Encodes the Ribosomal Protein L18 and Regulates Chloroplast Development in Rice.

Plastid ribosomal proteins play a crucial role in the growth and development of plants, mainly in the gene expression and translation of key genes in chloroplasts. While some information is known about the regulatory processes of plastid ribosomal proteins in various plant species, there is limited knowledge about the underlying mechanisms in rice. In this study, ethyl methanesulfonate (EMS) mutagenesis was used to generate a new mutant called wlp3 (white leaf and panicle3), characterized by white or albino leaves and panicles, which exhibited this phenotype from the second leaf stage until tillering. Furthermore, after a certain period, the newly emerging leaves developed the same phenotype as the rice variety ZH11, while the albino leaves of wlp3 showed an incomplete chloroplast structure and significantly low chlorophyll content. A transition mutation (T to C) at position 380 was identified in the coding region of the LOC_Os03g61260 gene, resulting in the substitution of isoleucine by threonine during translation. WLP3 encodes the ribosomal L18 subunit, which is localized in the chloroplast. Complementation experiments confirmed that LOC_Os03g61260 was responsible for the albino phenotype in rice. WLP3 has high expression in the coleoptile, leaves at the three-leaf stage, and panicles at the heading stage. Compared to the wild-type (WT), wlp3 exhibited reduced chlorophyll synthesis and significantly decreased expression levels of genes associated with plastid development. Yeast two-hybrid (Y2H) analysis revealed that WLP3 interacts with other ribosomal subunits, to influence chloroplast development. These results contribute to a better understanding of the underlying molecular mechanisms of chloroplast development and plastid gene translation.

Dielectric resonances of the cylindrical micro/nano cavity within epsilon-near-zero materials.

The dielectric resonances of spherically symmetric micro/nano cavity in zero-index materials have been systematically studied. However, the resonance properties of other shaped dielectric cavities in zero-index materials remain unclear. Here, we theoretically investigate the electromagnetic resonances of the dielectric cavity with cylindrical symmetry in the epsilon-near-zero materials. This kind of cavity supports a set of resonances with strong light confinement, including dipole, quadrupole and higher-order modes with multiple nodes. Furthermore, there is a redshift of the resonance wavelength with an increment of its size, obeying a law as the function of diameter and height. Also, we find that the redshift will be slower for higher-order modes. Through the infinite refractive index contrast and extra degree of freedom, they should have potential application in the enhancement of light-matter interaction and multiple-functional light manipulation in the integrated optical systems.

Combining hybrid nanoflowers with hybridization chain reaction for highly sensitive detection of SARS-CoV-2 nucleocapsid protein.

BACKGROUND: COVID-19 (coronavirus disease 2019) pandemic has had enormous social and economic impacts so far. The nucleocapsid protein (N protein) is highly conserved and is a key antigenic marker for the diagnosis of early SARS-CoV-2 infection. RESULTS: In this study, the N protein was first captured by an aptamer (Aptamer 58) coupled to magnetic beads (MBs), which in turn were bound to another DNA sequence containing the aptamer (Aptamer 48-Initiator). After adding 5'-biotinylated hairpin DNA Amplifier 1 and Amplifier 2 with cohesive ends for complementary hybridization, the Initiator in the Aptamer 48-Initiator began to trigger the hybridization chain reaction (HCR), generating multiple biotin-labeled DNA concatamers. When incubated with synthetic streptavidin-invertase-Ca3(PO4)2 hybrid nanoflower (SICa), DNA concatamers could specifically bind to SICa through biotin-streptavidin interaction with high affinity. After adding sucrose, invertase in SICa hydrolyzed sucrose to glucose, whose concentration could be directly read with a portable glucometer, and its concentration was positively correlated with the amount of captured N protein. The method is highly sensitive with a detection limit as low as 1 pg/mL. SIGNIFICANCE: We believe this study provided a practical solution for the early detection of SARS-CoV-2 infection, and offered a new method for detecting other viruses through different target proteins.

Starch chain-length distributions determine cooked foxtail millet texture and starch physicochemical properties.

Starch chain-length distributions play an important role in controlling cereal product texture and starch physicochemical properties. Cooked foxtail millet texture and starch physicochemical properties were investigated and correlated with starch chain-length distributions in eight foxtail millet varieties. The average chain lengths of amylopectin and amylose were in the range of DP 24-25 and DP 878-1128, respectively. The percentage of short amylopectin chains (Ap1) was negatively correlated with hardness but positively correlated with adhesiveness and cohesion. Conversely, the amount of amylose intermediate chains was positively correlated with hardness but negatively correlated with adhesiveness and cohesion. Additionally, the amount of amylose long chains was negatively correlated with adhesiveness and chewiness. The relative crystallinity (RC) of starch decreased with reductions in the length of amylopectin short chains in foxtail millet. Pasting properties were mainly influenced by the relative length of amylopectin side chains and the percentage of long amylopectin branches (Ap2). Longer amylopectin long chains resulted in lower gelatinization temperature and enthalpy (ΔH). The amount of starch branched chains had important effects on the gelatinization temperature range (ΔT). These results can provide guidance for breeders and food scientists in the selection of foxtail millet with improved quality properties.

Eosinophil dynamics during chemo-radiotherapy correlate to clinical outcome in stage â ¡-â £a nasopharyngeal carcinoma patients: Results from a large cohort study.

BACKGROUND AND PURPOSE: We investigated the dynamics of eosinophil depletion during definitive concurrent chemo-radiotherapy (CCRT) and their association with the prognosis of stage Ⅱ-Ⅳa nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Fuzzy C-means algorithm (FCMA) assessed longitudinal trends in circulating eosinophil counts (CECs) of 1225 patients throughout the period of radical radiotherapy. The prognostic impact on patients' survival was evaluated with Kaplan-Meier analysis and Cox proportional risk model was used to determine the hazard ratio for adverse prognostic effects in grades of eosinophil depletion. The interactive effect of pre-treatment CECs and CCRT on outcomes was evaluated using HRs within the framework of Cox regression models. RESULTS: Three grades of eosinophil depletion, as defined by the interaction between dynamic types of CECs in the period of treatment and the value of CECs at the termination of treatment, significantly stratified the poor prognosis in terms of progression-free survival (PFS), overall survival (OS), and distant metastasis-free survival (DMFS) [1.57-fold (P = 0.001), 1.69-fold (P = 0.007), and 1.51-fold (P = 0.019) for G1, 2.4-fold (P < 0.001), 2.76-fold (P < 0.001), and 2.31-fold (P < 0.001) for G2, as compared with G0]. Furthermore, high levels of pre-treatment CECs acted as the strongest protective factor against severe depletion grade (G0 vs. G2, HR = 0.20, P = 0.005; G1 vs. G2, HR = 0.14, P < 0.001). However, compared with radiotherapy alone, the benefit from CCRT was attenuated in patients with high pre-treatment CECs. CONCLUSIONS: CECs reduction after treatment in patients with NPC may be helpful in the clinical setting to aid in assessing the prognosis for standard treatment of NPC.

Melt-blown fiber felt for efficient all-weather recovery of viscous oil spills by Joule heating and photothermal effect.

Adsorbents play a vital role in responding to marine oil spills, yet effectively cleaning up viscous oil spills remains a technical challenge. Herein, we present a superhydrophobic oil-adsorbing felt prepared using melt-blown technology and functionally enhanced with a photoelectric composite CNT/PANI coating for effectively cleaning up high-viscosity oil spills. By virtue of its superior solar/Joule heating ability and thermally conductive fiber network, p-CNT/PANI@PP notably reduced crude oil viscosity and enhanced the oil diffusion coefficient within pores. Leveraging primarily solar heating and supplemented by Joule heating, p-CNT/PANI@PP demonstrates an impressive in-situ adsorption rate of up to 560 g/h for ultra-high-viscosity crude oil (c.a. 138000 mPa·s), alongside an adsorption capacity of 15.57 g/g. This measure enables efficient viscosity reduction and continuous day-and-night recovery of viscous crude oil, addressing the challenges posed by seasonal fluctuations in seawater temperature and adverse weather conditions. Moreover, a conveyorized collector integrated with an oil-adsorbing felt realizes continuous recovery of viscous oil spills with speed control to tackle varying thicknesses of oil film. Given the top-down material design, superior functionality, and applicability to applications, this work provides a comprehensive and feasible solution to catastrophic large-area viscous oil spills.

Spatial distribution characteristics of microplastics in the seawater column and sediments of the artificial reef area and adjacent water in Haizhou Bay.

Recently, scholars have been increasing concerned about microplastics (MPs). Unfortunately, information is lacking on the spatial distribution patterns of MPs in coastal seas; therefore, our understanding of the extent of offshore MP contamination remains incomplete. MP distribution in the seawater and surface sediments of an aquaculture area (AA), artificial reef area (AR), and comprehensive effect area (CEA) in Haizhou Bay were investigated in this study. The results showed that the mean abundances of MPs in the surface, middle and bottom seawater were 6.98 ± 3.01 n/m3, 9.12 ± 3.07 n/m3 and 10.20 ± 2.41 n/m3, respectively, and that the abundance in the sediment was 3.09 ± 1.16 n/g. The MP abundance in the bottom seawater was significantly higher than that in the surface seawater (P < 0.05). The correlation among MPs at different depths was not significant, but MPs in most habitats showed a significant correlation. We discovered a significant correlation between the abundance of MPs in the CEA seawater and AR sediments, but not between that in the CEA sediments and AR sediments. MPs can be transported from surface seawater to deeper layers by natural deposition processes. The horizontal transport of MPs due to the coastal gulf current and regular semidiurnal tides lead to the correlations observed in of MP abundance among the AA, CEA, and AR. Migration of MPs from the CEA to the AR was primarily caused by the southern eddies in Haizhou Bay, while migration of MPs from the sediment to the seawater could be due to upwelling in the AR. This was also the main reason there was a lack of a correlation between the sediment from the AR and the seawater from the CEA. This work provides a theoretical and empirical foundation for MP transport and source tracking.

RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.

Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-ß-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-ß-induced cell viability, decreased TGF-ß-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-ß-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-ß, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

A cause-effect relationship between Graves' disease and the gut microbiome contributes to the thyroid-gut axis: A bidirectional two-sample Mendelian randomization study.

Background: An association between Graves' disease (GD) and the gut microbiome has been identified, but the causal effect between them remains unclear. Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between GD and the gut microbiome. Gut microbiome data were derived from samples from a range of different ethnicities (18,340 samples) and data on GD were obtained from samples of Asian ethnicity (212,453 samples). Single nucleotide polymorphisms (SNPs) were selected as instrumental variables according to different criteria. They were used to evaluate the causal effect between exposures and outcomes through inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger, and simple mode methods. F-statistics and sensitivity analyses were performed to evaluate bias and reliability. Results: In total, 1,560 instrumental variables were extracted from the gut microbiome data (p< 1 × 105). The classes Deltaproteobacteria [odds ratio (OR) = 3.603] and Mollicutes, as well as the genera Ruminococcus torques group, Oxalobacter, and Ruminococcaceae UCG 011 were identified as risk factors for GD. The family Peptococcaceae and the genus Anaerostipes (OR = 0.489) were protective factors for GD. In addition, 13 instrumental variables were extracted from GD (p< 1 × 10-8), causing one family and eight genera to be regulated. The genus Clostridium innocuum group (p = 0.024, OR = 0.918) and Anaerofilum (p = 0.049, OR = 1.584) had the greatest probability of being regulated. Significant bias, heterogeneity, and horizontal pleiotropy were not detected. Conclusion: A causal effect relationship exists between GD and the gut microbiome, demonstrating regulatory activity and interactions, and thus providing evidence supporting the involvement of a thyroid-gut axis.

Research on Embodied Carbon Transfer Measurement and Carbon Compensation among Regions in China.

The existence of interprovincial embodied carbon transfer not only makes it difficult to achieve carbon emission reductions but also exacerbates the inequity, inefficiency, and high costs of interprovincial carbon emission reduction rights and responsibilities. This paper uses multi-regional input-output analysis (MRIOA) to measure the interprovincial embodied carbon transfer in 2017, obtains the net carbon transfer between 30 provinces (municipalities and autonomous regions) and eight regions in 2017, and accounts for the interprovincial carbon compensation amount based on the carbon price in the national carbon market. This study finds that carbon transfer from economically developed provinces to less developed provinces still exists in China, and the overall distribution shows a spatial transfer pattern from south to north and from east to west, with the northwestern region bearing most of the carbon emission pressure for which it should receive corresponding financial compensation. As part of the process to achieve the "dual carbon" target, appropriate emission reduction policies should be formulated according to the characteristics of provincial carbon transfer and the principle of "who benefits, who compensates", and economically developed regions should give corresponding financial or technical compensation to less developed regions based on net carbon transfer. Compensation and support should be given to less developed regions based on net carbon transfer to prevent further regional development imbalances.

The miR-103a-3p/TGFBR3 axis regulates TGF-ß-induced orbital fibroblast activation and fibrosis in thyroid-eye disease.

Molecular pathways that contribute to orbital fibroblast activation during thyroid-eye disease (TED) may promote TED progression. Non-coding RNAs, especially miRNAs, play a critical role in the pathogenesis of TED. In the present study, miR-103a-3p was dramatically upregulated and TGFBR3 was downregulated within TED orbital tissue samples and TGF-ß-stimulated TED orbital fibroblasts. miR-103a-3p inhibition in TGF-ß-stimulated TED orbital fibroblasts partially abolished TGF-ß-induced fibrotic alterations, as manifested by the impaired fibroblast cell viability and decreased vimentin and fibronectin levels. miR-103a-3p directly targeted TGFBR3 in TED orbital samples and TGF-ß-stimulated TED orbital fibroblasts. In TGF-ß-stimulated TED orbital fibroblasts, TGFBR3 overexpression inhibited fibroblast cell viability and decreased vimentin and fibronectin levels. TGFBR3 overexpression partially attenuated the inhibitory effects of miR-103a-3p overexpression on TGFBR3 expression and the promotive effects of miR-103a-3p overexpression on TGF-ß-induced fibrotic alterations. Under TGF-ß stimulation, miR-103a-3p overexpression significantly promoted, whereas TGFBR3 overexpression inhibited the phosphorylation of Erk1/2, JNK, Smad2, and Smad3. TGFBR3 overexpression also partially abolished the effects of miR-103a-3p overexpression on Erk1/2, JNK, Smad2, and Smad3 phosphorylation. In conclusion, the miR-103a-3p/TGFBR3 axis regulated TGF-ß-induced TED orbital fibroblast activation and fibrosis in TED, with the possible involvement of the Erk/JNK and TGF-ß/Smad signaling pathways.

Sex difference on fibroblast growth factors (FGFs) expression in skin and wound of streptozotocin(STZ)-induced type 1 diabetic mice.

BACKGROUND: Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family's expression patterns in skin and wounds influenced by both diabetes and sex are still unknown. METHODS AND RESULTS: In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family's expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgf expressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) - a FGFR activation marker gene - in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury). CONCLUSION: Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.

The different ways microplastics from the water column and sediment accumulate in fish in Haizhou Bay.

Global microplastic (MP) pollution is a serious environmental problem that has been found in various ecosystems, especially marine ecosystems. In this study, the water (surface, middle and bottom water), sediment and fish (pelagic, demersal and benthic fish) in the artificial reef area and adjacent waters in Haizhou Bay were collected, and the mechanism of MP transmission among the three media was analyzed. The results showed that >96 % of the plastics in the region were MPs. The shape of MPs was mainly fibrous (water (73.3 %), sediment (56 %), fish (95.3 %)), color was mainly blue (water (49.3 %), sediment (47 %), fish (72.3 %)), and the material was mainly PET (water (39.6 %), sediment (33 %), fish (86.6 %)). We found that, except for the natural deposition of MPs, MPs could be ingested by pelagic fish and transmitted through vertical movement in the water, while there was an interaction between MPs in benthic fishes and the middle-bottom waters. In addition, as relevant variables, body length and body weight were more likely to explain the number of MPs ingested by fishes than were δ13C and δ15N. Therefore, based on the linear relationship between δ15N and body length, we concluded that there was a weak trophic magnification effect of MPs ingested by fish in this region. This study provides unique information for further exploring the factors influencing the spatial distribution of MPs and the transmission mechanism of MPs in fish.