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Objectives: To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and methods: This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. Results: In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. Conclusion: CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. Critical relevance statement: Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. Key Points: Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency. [ABSTRACT FROM AUTHOR]

Perovskite solar cells (PSCs) have seen remarkable progress in recent years, largely attributed to various additives that enhance both efficiency and stability. Among these, fluorine-containing additives have garnered significant interest because of their unique hydrophobic properties, effective defect passivation, and regulation capability on the crystallization process. However, a targeted structural approach to design such additives is necessary to further enhance the performance of PSCs. Here, fluoroalkyl ethylene with different fluoroalkyl chain lengths (CH2CH(CF2)nCF3, n = 3, 5, and 7) as liquid additives is used to investigate influences of fluoroalkyl chain lengths on crystallization regulation and defect passivation. The findings indicate that optimizing the quantity of F groups plays a crucial role in regulating the electron cloud distribution within the additive molecules. This optimization fosters strong hydrogen bonds and coordination effects with FA+ and uncoordinated Pb2+, ultimately enhancing crystal quality and device performance. Notably, 1H,1H,2H-perfluoro-1-hexene (PF3) with the optimal number of F presents the most effective modulation effect. A PSC utilizing PF3 achieves an efficiency of 24.05%, and exhibits exceptional stability against humidity and thermal fluctuations. This work sheds light on the importance of tailored structure designs in additives for achieving high-performance PSCs. [ABSTRACT FROM AUTHOR]

The parent HZSM-5 was modified with oxide M (M = Fe, Cu, La, P) via the incipient impregnation method by using ferric nitrate, copper nitrate, lanthanum nitrate and diammonium hydrogen phosphate as precursors to prepare a series of oxide M modified HZSM-5 (M/HZSM-5). And the M/HZSM-5 used as solid acid was physically mixed with commercial Cu/ZnO/Al2O3 to obtain bifunctional catalysts for steam reforming of dimethyl ether (SRD) reaction. The samples were systematically characterized by XRD, FTIR, N2 adsorption–desorption, and NH3-TPD techniques. The results showed that HZSM-5 structure remained basically unchanged after it was modified by oxide M; however, its specific surface area, pore volume, total acid amount, especially strong acid amount was decreased, and then affecting the DME conversion, H2 yield and carbon-containing product selectivity of the corresponding bifunctional catalyst. Among them, the bifunctional catalyst composed of Cu/ZnO/Al2O3 and La/HZSM-5 with the larger specific surface area and lower strong acid sites showed best SRD performance, and the dimethyl ether conversion and H2 yield reached 90.4% and 73.9% at TOS of 10 h under the conditions of reaction temperature 300 °C, pressure 0.1 MPa, space velocity 5000 mL/(g h), respectively. [ABSTRACT FROM AUTHOR]

This paper focuses on the fault-tolerant consensus problem for a class of nonlinear multi-agent systems subject to channel noises and actuator/sensor faults in the presence of the denial-of-service (DoS) attacks. Different from existing results, we propose a novel estimation/control algorithm to deal with the unknown states, faults, noises and DoS attacks, simultaneously. For the estimation process, a class of complementary dynamic sector regions depending on the system measurements is first developed. In these regions, a novel distributed proportional-integral observer is constructed. To suppress the lag caused by persistent integration, a reset dynamic derived from the above sector regions is selected and then combined with the observer. The corresponding reset behavior can interrupt the integral process of observer, which enhances the systems transient performance. Based on the method, the states, faults and noises can be quickly estimated. For the control process, a fault-tolerant controller with the dynamic compensation and reset mechanism is designed. The reset behavior improves the compensation effect for the faults, noises and DoS attacks, which restrains the negative impact of the unknown inputs. This finally achieves the objective of the leader-follower consensus. The effectiveness of the proposed strategy is illustrated by simulation results. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked to the multiple organ dysfunction triggered by OSA. However, the role of the CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through the construction of the OSA classic model, we found that the colon tissue of chronic intermittent hypoxia (CIH)–induced mice exhibited an overexpression of the CB1 receptor. The results of hematoxylin-eosin staining and transmission electron microscopy revealed that inhibition of the CB1 receptor could decrease the gap between the mucosa and muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, and promote the recovery of tight junctions of CIH-induced mice. Furthermore, CB1 receptor inhibition reduced the levels of metabolic endotoxemia and inflammatory responses, exhibiting significant protective effects on the colon injury caused by CIH. At the molecular level, through western blotting and real-time polymerase chain reaction techniques, we found that inhibiting the CB1 receptor can significantly increase the expression of ZO-1 and Occludin proteins, which are closely related to the maintenance of intestinal mucosal barrier function. Through 16S rRNA high-throughput sequencing and short-chain fatty acid (SCFA) determination, we found that inhibition of the CB1 receptor increased the diversity of the microbial flora and controlled the makeup of intestinal flora. Moreover, butyric acid concentration and the amount of SCFA-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, were both markedly elevated by CB1 receptor inhibition. The results of the spearman correlation study indicated that Lachnospiraceae showed a positive association with both ZO-1 and Occludin but was negatively correlated with the colon CB1 receptor, IL-1β, and TNF-α. According to this study, we found that inhibiting CB1 receptor can improve CIH-induced colon injury by regulating gut microbiota, reducing mucosal damage and promoting tight junction recovery. Key points: •CIH leads to overexpression of CB1 receptor in colon tissue. •CIH causes intestinal flora disorder, intestinal mucosal damage, and disruption of tight junctions. •Inhibition of CB1 receptor can alleviate the colon injury caused by CIH through regulating the gut microbiota, reducing mucosal injury, and promoting tight junction recovery. [ABSTRACT FROM AUTHOR]

Clinical trials have demonstrated the potential neuroprotective effects of uric acid (UA) in Alzheimer's disease (AD). However, the specific mechanism underlying the neuroprotective effect of UA remains unclear. In the present study, we investigated the neuroprotective effect and underlying mechanism of UA in AD mouse models. Various behavioral tests including an elevated plus maze, Barnes maze, and Morris water maze were conducted to evaluate the impact of UA on cognitive function in β-amyloid (Aβ) microinjection and APP23/PS45 double transgenic mice models of AD. Immunohistochemical staining was employed to visualize pathological changes in the brains of AD model mice. Western blotting and immunofluorescence techniques were used to assess levels of autophagy-related proteins and transcription factor EB (TFEB)-related signaling pathways. BV2 cells were used to investigate the association between UA and microglial autophagy. We reported that UA treatment significantly alleviated memory decline in Aβ-induced AD model mice and APP23/PS45 double transgenic AD model mice. Furthermore, UA activated microglia and upregulated the autophagy-related proteins such as LC3II/I ratio, Beclin-1, and LAMP1 in the hippocampus of AD model mice. Similarly, UA protected BV2 cells from Aβ toxicity by upregulating the expressions of Beclin-1, LAMP1, and the LC3II/I ratio, whereas genetic inhibition of TFEB completely abolished these protective effects. Our results indicate that UA may serve as a novel activator of TFEB to induce microglia autophagy and facilitate Aβ degradation, thereby improving cognitive function in AD model mice. Therefore, these findings suggest that UA may be a novel therapeutic agent for AD treatment. [ABSTRACT FROM AUTHOR]

Adolescents with borderline personality disorder (BPD) may have impaired executive functions. There are few functional MRI (fMRI) studies in adolescents with BPD and the neuroimaging markers of this disorder are unknown. The aim of this study was to investigate the functional connectivity (FC) of BPD in adolescents, and to explore the relationship between FC changes and executive function in adolescents with BPD. 50 adolescents aged 12 to 17 years with BPD and 21 gender-and-age matched healthy controls (HC) were enrolled into the study. Brain MRI scan including a 3D-T1 weighted structural sequence and a resting-state fMRI was acquired. A seed-based FC analysis was performed. We used the Stroop color-word test (SCWT) and the trail making test (TMT) to evaluate the executive function of the participants. Correlative analysis of FC alterations with executive function and clinical symptoms was also performed. Compared to the HCs, adolescents with BPD showed increased FC in the limbic—cortical circuit, such as the FC between the left hippocampus and right parahippocampal gyrus, between the right middle occipital gyrus and the left middle temporal gyrus, and between the left medial superior frontal gyrus and the right inferior temporal gyrus. FC in the default mode network (DMN) was decreased between the left angular gyrus and the left precuneus but increased between the left angular gyrus and the right anterior cingulate cortex (voxel P < 0.001, cluster P < 0.05, FWE corrected). The BPD group demonstrated significantly lower cognitive testing scores than the HC group on the SCWT-A (P < 0.001), SCWT-B (P < 0.001), and SCWT-C (P = 0.034). The FC alterations between limbic system and cortical regions were associated with SCWT and TMT (P < 0.05). FC alterations were noted in both limbic—cortical circuit and DMN in adolescents with BPD, which were associated with impaired executive function. This study implicated the FC alterations as the neural correlates of executive functioning in adolescents with BPD. [ABSTRACT FROM AUTHOR]

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses. [ABSTRACT FROM AUTHOR]

A bipartite graph Γ is a bi-Cayley graph over a group H if H ⩽ Aut Γ acts regularly on each part of Γ . A bi-Cayley graph Γ is said to be a normal bi-Cayley graph over H if H ⊴ Aut Γ , and bi-primitive if the bipartition preserving subgroup of Aut Γ acts primitively on each part of Γ . In this paper, a classification is given for 2-arc-transitive bi-Cayley graphs which are bi-primitive and non-normal. [ABSTRACT FROM AUTHOR]

For the serious situation of heavy metal pollution, the use of cheap, clean, and efficient biochar to immobilize heavy metals is a good treatment method. In this paper, SA@ZIF-8/BC was prepared for the adsorption of Pb2+ in solution using sodium alginate (SA) and zeolitic imidazolate framework-8 (ZIF-8) modified corn cob biochar. The results showed that the specific surface area of modified biochar was greatly improved, with good adsorption capacity for Pb2+, strong anti-interference ability, and good economy. At the optimal adsorption pH of 5, the adsorption model of Pb2+ by SA@ZIF-8/BC was more consistent with the pseudo-second-order kinetic model and Langmuir isotherm model. This indicates that the adsorption of Pb2+ by SA@ZIF-8/BC is chemisorption and monolayer adsorption. The maximum adsorption of modified biochar was 300 mg g−1, which was 2.38 times higher than that of before modified BC (126 mg g−1). The shift in binding energy of functional groups before and after adsorption of SA@ZIF-8/BC was studied by XPS, and it was found that hydroxyl and carboxyl groups played an important role in the adsorption of Pb2+. It was demonstrated that this novel adsorbent can be effectively used for the treatment of Pb pollution in wastewater. [ABSTRACT FROM AUTHOR]

Key message: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes. [ABSTRACT FROM AUTHOR]

The tip-clearance flow in a pump-jet propulsor exerts great impacts on the fluctuating pressures and resultant unsteady forces, which are important sources of structural vibrations and radiated noise underwater. The blade geometry close to the tip is an important factor determining the vortex strength in the tip-clearance flow. In the open-water condition, the effects of raking the rotor tips on the duct-surface fluctuating pressures and the resultant unsteady forces acting on different components of the propulsor are investigated via physical model experiments and the numerical solution of Reynolds-averaged Navier-Stokes (RANS) equations coupled with the SST k - ω turbulence model. The measured and simulated results of hydrodynamic pressures are consistent to each other, and the simulated flows help better understand why the fluctuating pressures change with the tip geometry. The strong fluctuations of duct-surface pressures are caused by intensive tip separation vortices. The duct-surface pressure fluctuations are effectively reduced by using the rake distribution near the tip towards blade back side and, for the combination of the five-bladed rotor and the seven-bladed stator, the resultant unsteady horizontal (and vertical) forces acting on the duct and stator are also reduced; while increasing rake leads to negative effect on pressure fluctuations and unsteady horizontal (and vertical) forces acting on all the components of the propulsor. [ABSTRACT FROM AUTHOR]

Multiple infections are a key component of HPV pathogenesis and have a direct impact on how an infection turns out. It's crucial to look at the associations between HPV multiple infections and both age and HPV genotypes in the Chinese population, searching for the causative factors of multiple infections with a view to providing new ideas for the treatment and prevention of multiple infections. In this study, we retrospectively analyzed the data of HPV infections among outpatients from the 2019 year to the 2021 year of Shandong Maternal and Child Health Hospital. Analyzed the correlation between HPV multiple infections and age using logistic regression. Differences in the percentage of multiple infections between age groups were compared using the chi-square test. The chi-square test compared the differences in the distribution of 15 common HPV genotypes in mono- versus multiple infections. A two-dimensional matrix presented the frequency of HPV genotype combinations. Logistics regression analysis showed that age was significantly associated with the occurrence of multiple infections, with a dominance ratio OR 1.026 (95% CI 1.02–1.04). Interestingly, the proportion of HPV multiple infections among HPV-positive individuals increases with age in people older than 30 years of age. The chi-square test showed there was a difference in the distribution of HPV genotypes between multiple infections and mono- HPV infection (χ2 = 76.4; p = 0.000), a difference in the composition of HPV genotypes for dual versus single infections (χ2 = 90.6; p = 0.000) and a difference in HPV genotypes for triple versus single infections (χ2 = 56.7; p = 0.000). A 2 × 2 matrix showed that the combination of HPV52/HPV58 (30; 6.4%) was the combination of the highest frequency of infection for dual infections; The HPV52/HPV58 (21; 4.8%) combination was the highest frequency of HPV triple infection combination. HPV multiple infections were positively correlated with age; increasing age was positively correlated with the proportion of HPV multiple infections in the total infected population; the distribution of the 15 common genotypes of HPV differed between multiple infections and single infections; and HPV52:58 was a common type of infection combination in the Shandong population. [ABSTRACT FROM AUTHOR]

Cu-Co/X-MMT (X = Na, SiO2) catalysts were prepared via impregnation method using Na-MMT and SiO2-MMT (montmorillonite pillared by SiO2) as the support and copper nitrate and cobalt nitrate as precursors. In addition, the citric acid was introduced during the preparation of Cu-Co/SiO2-MMT to obtain Cu-Co/SiO2-MMT-Ac catalyst. The catalysts were characterized by XRD, TEM, H2-TPR, XPS and N2 adsorption–desorption at low temperature. The results showed that the acidity and specific surface area of SiO2-MMT were larger than those of Na-MMT, thus resulting in dimethyl ether (DME) conversion and H2 yield of Cu-Co/SiO2-MMT higher than those of Cu-Co/Na-MMT during steam reforming of DME (SRD). However, for Cu-Co/SiO2-MMT, there was a large amount of methanol in the carbon-containing product due to the large particle size of Cu. The Cu particle size of Cu-Co/SiO2-MMT-Ac was decreased significantly due to the introduction of citric acid, thus accelerating the steam reforming of methanol reaction and enabling the timely conversion of the intermediate product methanol of SRD, resulting in the increasing DME conversion and H2 yield. Therefore, Cu-Co/SiO2-MMT-Ac was expected to be a potential catalyst for SRD. [ABSTRACT FROM AUTHOR]

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance. SH3RF2 suppresses RBPMS stability to promote AP-1 transactivation, and thereby contributes to cisplatin resistance in ovarian cancer cells [ABSTRACT FROM AUTHOR]

3D curved slot structures have a wide range of applications in the aerospace field, which have large material removal, small wall thickness, and are mostly manufactured by five-axis process. Trochoidal milling has become an effective method to process such parts because of the low and stable milling force and high machining efficiency. However, unlike the three-axis trochoidal milling of flat slots, the five-axis machining introduces additional rotation axes, which complicates the control of the machining process. Due to the complex double sidewall structure of 3D curved slots, tool interference and singularity issues will easily occur during machining, which will reduce the machining efficiency and the workpiece quality. In view of the above problems, this study proposes a non-singular five-axis trochoidal milling process method for 3D curved slots. Firstly, the trochoidal cutter location (CL) path model is established in the 2D parameter domain of the bottom surface. Meanwhile, an efficient interference-free tool orientation planning method is proposed based on the theory of vector rotation and quadratic interpolation. Then, the optimization strategy of the workpiece clamping orientation is proposed to avoid singularity and improve machining efficiency. Finally, the effectiveness of the proposed method is verified by simulation and experiment, and the result shows that the processing efficiency of the proposed method is improved by 71.5%. The proposed process method provides a useful idea for high efficiency NC machining of 3D curved slot parts. [ABSTRACT FROM AUTHOR]

Background and objectives: Non-suicidal self-injury (NSSI) behavior is one of the characteristics of borderline personality disorder (BPD) in adolescents. Prior studies have shown that adolescents with BPD may have a unique pattern of brain alterations. The purpose of this study was to investigate the alterations in brain structure and function including gray matter volume and resting-state functional connectivity in adolescents with BPD, and to assess the association between NSSI behavior and brain changes on neuroimaging in adolescents with BPD. Methods: 53 adolescents with BPD aged 12–17 years and 39 age–gender matched healthy controls (HCs) were enrolled into this study. Brain magnetic resonance imaging (MRI) was acquired with both 3D-T1 weighted structural imaging and resting-state functional imaging. Voxel-based morphometry (VBM) analysis for gray matter volume and seed-based functional connectivity (FC) analysis were performed for assessing gray matter volume and FC. Clinical assessment for NSSI, mood, and depression was also obtained. Correlative analysis of gray matter alterations with self-injury or mood scales were performed. Results: There were reductions of gray matter volume in the limbic-cortical circuit and default mode network in adolescents with BPD as compared to HCs (FWE P < 0.05, cluster size ≥ 1000). The diminished gray matter volumes in the left putamen and left middle occipital gyrus were negatively correlated with NSSI in adolescents with BPD (r = − 0.277 and P = 0.045, r = − 0.422 and P = 0.002, respectively). Furthermore, there were alterations of FC in these two regions with diminished gray matter volumes (voxel P < 0.001, cluster P < 0.05, FWE corrected). Conclusions: Our results suggest that diminished gray matter volume of the limbic-cortical circuit and default mode network may be an important neural correlate in adolescent BPD. In addition, the reduced gray matter volume and the altered functional connectivity may be associated with NSSI behavior in adolescents with BPD. [ABSTRACT FROM AUTHOR]

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments.Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses. [ABSTRACT FROM AUTHOR]

Declines in oral consumption and swallowing function are common reasons which may elevate the risk of malnutrition in the older adults. This study aimed to provide valuable information and contribute to the existing body of knowledge in this field as well as highlight the importance of a comprehensive assessment of oral health, swallowing function, and nutritional status in long-term care residents. This was a cross-sectional study. Thirty-nine participants were recruited from a nursing home. The comprehensive assessment was evaluated in participants, including oral health (Oral Health Assessment Tool (OHAT)), swallowing function (Functional Oral Intake Scale (FOIS) and Eating Assessment Tool (EAT)-10), and nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF). The average age of participants was 80.4 ± 11.7 years, and 46% of these older adults were found to be at the risk of malnutrition. There was a negative correlation between the OHAT and MNA-SF scores. In addition, subjects with poor oral health (OHAT score = 5~8), oral consumption of a modified diet (FOIS score = 4~6), and reduced swallowing function (EAT-10 score ≥ 3) were more likely to be at risk of malnutrition. A comprehensive evaluation of oral health and swallowing function was closely connected with the nutritional status of older nursing home dwellers. [ABSTRACT FROM AUTHOR]

Artificial light at night (ALAN) is a growing environmental hazard with economic, ecological, and public health implications. Previous studies suggested a higher burden of light pollution and related adverse effects in disadvantaged communities. It is critical to characterize the geographic distribution and temporal trend of ALAN and identify associated demographic and socioeconomic factors at the population level to lay the foundation for environmental and public health monitoring and policy-making. We used satellite data from the Black Marble suite to characterize ALAN in all counties in contiguous US and reported considerable variations in ALAN spatiotemporal patterns between 2012 and 2019. As expected, ALAN levels were generally higher in metropolitan and coastal areas; however, several rural counties in Texas experienced remarkable increase in ALAN since 2012, while population-level ALAN burden also increased substantially in many metropolitan areas. Importantly, we found that during this period, although the overall ALAN levels in the USA declined modestly, the temporal trend of ALAN varied across areas with different racial/ethnic compositions: counties with a higher percentage of racial/ethnic minority groups, particularly Hispanic populations, exhibited significantly less decline. As a result, the differences in ALAN levels, as measured by the Black Marble product, across racial/ethnic groups became larger between 2012 and 2019. In conclusion, our study documented variations in ALAN spatiotemporal patterns across America and identified multiple population correlates of ALAN patterns that warrant further investigations. Future studies should identify underlying factors (e.g., economic development and decline, urban planning, and transition to newer lighting technologies such as light emitting diodes) that may have contributed to ALAN disparities in the USA. [ABSTRACT FROM AUTHOR]

The hilly area of red soil in the central subtropical region of China has a long history of severe soil erosion due to its abundance of water, heat, and intense agricultural and forestry activities. The Sandshale red soil area is hot and rainy, the local land utilization rate and replanting index are high, and the soil easily weathers and erodes, resulting in infertile and sandy soils, extensive soil erosion and large erosion, with far-reaching impacts. In this study, the stability of soil aggregates was studied by the wet sieving method and Le Bissonais (LB) method in six land use patterns in the Sandshale red soil area, including natural forest (NF), Pinus massoniana (PM), Eucalyptus urophylla × E. grandis (EU), orchard (OR), wasteland (WL) and arable land (AL). The transport damage characteristics of the soil aggregates under concentrated water flow were analyzed by using the soil aggregates to simulate the soil surface roughness in the field using a steel scouring flume with a variable slope. The results showed that: (1) the total soil porosity of the natural forest was the highest, with 56.51% in A layer, which was 4.99% higher than the B layer, and the organic matter content ranged from 10.69 to 29.94 g.kg−1 and was highest in NF and lowest in AL; (2) the maximum mean weight diameter (MWD) obtained by the wet sieving method was 4.81 mm for natural forest, and the MWD was the lowest in OR and AL at 2.45–2.77 mm. The MWD measured by the LB method was also highest in NF and lowest in AL. The contents of Fed and Ald have a strong correlation with the stability parameters of soil aggregates; (3) the Wr/Wi results for the six land use patterns were NF>PM>EU> WL>OR>AL; the NF had the strongest soil aggregate stability, followed by WL, PM and EU, and AL and OR had the weakest; the stability of soil aggregates gradually weakened as the soil depth increased. Comprehensive analysis shows that forest land has high soil stability and obvious advantages in soil erosion resistance. Strengthening the construction of artificial forests can be an important means to reduce soil erosion in red soil hilly region. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood. Methods: We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship. Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication. Results: Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses. Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking. Genetically predicted methylation at CpG site cg17823346 [ZMIZ1] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk. Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ZMIZ1] as well as cg02149899 and CRC risk. Discussion: Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the "Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy"(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables. Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. Here, the authors investigate the genetic basis of gene expression in skin biopsies from psoriasis patients and interactions with inflammation to better understand mechanisms of the disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. Methods: Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. Results: At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. Conclusion: This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches. [ABSTRACT FROM AUTHOR]

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia. [ABSTRACT FROM AUTHOR]

The (Fe82Al13.5Ga4.5)99.9(NbC)0.1 sheets with strong Goss texture and large magnetostriction were prepared by rolling and isothermal annealing processes. Single Goss grain growth was observed in sheets undergoing isothermal annealing at 1050 °C for 1 h using Ar as protecting gas. With annealing time increasing to 8 h at 1050 °C, a largest magnetostriction of 154 × 10−6 is obtained in sheet and a large λ// (the maximum magnetostriction with magnetic field parallel to rolling direction) of 160 × 10−6 along the rolling direction is also observed. The fact that a λ// of 160 × 10−6 along RD can be achieved with only 4.5 at% Ga in the Fe-18 at% (Al, Ga) sheet is of practical importance. Compared with previous studies in Fe–Al and Fe–Ga sheets, this paper provides a more efficient approach to prepare strong Goss textured sheets. In this way, a slow continuous heating process, sulfur-induced surface energy control and high-temperature annealing above 1200 °C are no more necessary. It shows a good prospect for industrial production of high-performance magnetostrictive alloy sheets. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.Imaging mass cytometry is used to map the multicellular dynamics of immune checkpoint blockade-treated triple-negative breast cancer, finding that key proliferative fractions and cell–cell interactions drive response, and immunotherapy distinctively remodels tumour structure. [ABSTRACT FROM AUTHOR]

Secernin-1 (SCRN1) is a regulator of exocytosis in mast cells. Recently, SCRN1 was reported to be correlated with the prognosis of colorectal cancer and gastric cancer, but its functional effects on oral squamous cell carcinoma (OSCC) remain unclear. Our aim was to explore the expression pattern and the migration and invasion effects of the newly identified SCRN1 in OSCC. Western blotting (WB) was performed to measure SCRN1 expression in human OSCC tissue samples and OSCC cell lines. The effects of SCRN1 on OSCC cell proliferation, invasion and migration were analyzed by cell counting kit-8 and Transwell assays. The expression levels of TGF-β, Smad3 and phosphorylated Smad3 (p-Smad3) were measured by WB. The secretion of matrix metalloproteinase (MMP)-2 and MMP-9 was determined by the enzyme-linked immunosorbent assay. The expression of SCRN1 was significantly elevated in OSCC tissues and cell lines. SCRN1 knockdown reduced the expression of TGF-β and p-Smad3 in OSCC cells. TGF-β stimulation promoted proliferation, invasion and migration and enhanced the expression of p-Smad3 and the secretion of MMP9 in SCRN1-knockdown OSCC cell lines. Our study demonstrated that SCRN1 is upregulated in OSCC. Further analyses demonstrated that SCRN1 promotes the proliferation, invasion and migration of OSCC cells via TGF-β/Smad3 signaling. [ABSTRACT FROM AUTHOR]

Inspired to the work of Ma and Wu (Discrete Contin Dyn Syst 31:545–557, 2011) and Climenhaga (Ergodic Theory Dyn Syst 31(4):1163–1182, 2011), we introduce the new notions of topological pressure and upper (lower) capacity topological pressure of a free semigroup action of maps for finite potential functions by using the Carathéodory–Pesin structure (C-P structure) with respect to non-compact sets in this paper. Meanwhile, we also give some properties of these notions. Moreover, by Bowen's equation, we characterize the Hausdorff dimension of certain sets, whose points have the positive lower Lyapunov exponents and satisfy a so-called tempered contraction condition. [ABSTRACT FROM AUTHOR]

The Arctic tundra is a relatively young and new type of biome and is especially sensitive to the impacts of global warming. However, little is known about how the Arctic flora was shaped over time. Here we investigate the origin and evolutionary dynamics of the Arctic flora by sampling 32 angiosperm clades that together encompass 3626 species. We show that dispersal into the Arctic and in situ diversification within the Arctic have similar trends through time, initiating at approximately 10–9 Ma, increasing sharply around 2.6 Ma, and peaking around 1.0–0.7 Ma. Additionally, we discover the existence of a long-term dispersal corridor between the Arctic and western North America. Our results suggest that the initiation and diversification of the Arctic flora might have been jointly driven by progressive landscape and climate changes and sea-level fluctuations since the early Late Miocene. These findings have important conservation implications given rapidly changing climate conditions in the Arctic. The Arctic tundra is a relatively young biome. Here, the authors sample 32 angiosperm clades encompassing 3600+ species and find that both long-term dispersal and in situ speciation may have contributed to Arctic flora assembly, in association with landscape, climate and sea-level changes since the early Late Miocene. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer is a malignant tumor with obvious genetic predisposition. Association studies have proposed that rs2853677, a SNP localizing at intron region of TERT (telomerase reverse transcriptase), is significantly associated with TERT expression, telomere length and eventually lung cancer risk. However, functional genomics work indicates that rs2853677 is not with the ability to alter gene expression. All these facts make us hypothesize that some other genetic variation(s) are in linkage disequilibrium (LD) with rs2853677 and influence TERT expression. Methods: LD pattern in rs2853677 nearby region was analyzed based on 1000 genomes data for three representative populations in the world and functional genomics research was performed for this locus. Results: Only one SNP, rs2736099, is in strong LD with rs2853677 in East Asian. Dual-luciferase reporter assay verifies that rs2736099 can regulate gene expression and should be the causal SNP for this disease. Through chromosome conformation capture assay, it is disclosed that the enhancer surrounding rs2736099 can interact with TERT promoter. Through chromatin immunoprecipitation, the transcription factor SP1 (Sp1 transcription factor) is recognized for the chromatin segment spanning rs2736099. Conclusions: Our results provide the missing piece between genetic variation at this locus and lung cancer risk, which is also applied to tumorigenesis in other tissues and cell proliferation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). Methods: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24–36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. Results: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123–1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017–1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. Conclusion: Increased NLR measured within 24–36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality. [ABSTRACT FROM AUTHOR]

Policy decision of curling refers to providing strategy suggestions for curling competition with the help of computers. Existing curling agents have achieved good results in the digital scenarios, but cannot make correct decisions when applied to actual competition and training scenes. In this paper, a strategies decision agent in the real scene has been proposed. The competition situation was acquired by a Situation-Aware Network and mapped by a Digital Extraction module. We designed Curling MCTS to explore the best strategy in continuous space. The effectiveness of our framework has been verified by experiments and evaluated by China's wheelchair curling team at China Disabled Sports Management Center. With the help of our system, China's wheelchair curling team trained effectively and won the championship in the XIII Paralympic Winter Games (2022, Beijing). In addition, a new curling target detection dataset was provided. [ABSTRACT FROM AUTHOR]

There is no conclusion on whether green development can symbiotically coexist with shared development, and the effect of environmental protection tax on labor share provides new evidence to answer this question. This paper presents a theoretical analysis of change in labor share in the exogenous impact of the enforcement of the Environmental Protection Tax Law of China, and proposes relevant hypotheses. At the same time, empirical data of listed firms on the main board from 2013 to 2019 are collected. A difference-in-differences model is constructed to test the hypotheses empirically. The study found that the reform of environmental protection fee to tax reduced the labor share of high-polluting firms by an average of about 1.43%. However, it did not significantly reduce the share of corporate executives' income. The reform of environmental protection fee to tax reduces the labor share of high-polluting firms through the crowding-out effect and the substitution effect of production technology. The heterogeneity study revealed that the reform of environmental protection fee to tax has more substantial negative impacts on firms with high financing constraints, low market concerns, and low government subsidies. There is no significant difference between the impact on state-owned and private firms. The reform of environmental protection fee to tax has a more substantial negative impact on the firms in Central and Western China than those in more economically developed Eastern China. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental disorders characterized by impaired social interaction skills. Whole exome sequencing has identified loss-of-function mutations in lysine methyltransferase 2E (KMT2E, also named MLL5) in ASD patients and it is listed as an ASD high-risk gene in humans. However, experimental evidence of KMT2E in association with ASD-like manifestations or neuronal function is still missing. Relying on KMT2E+/− mice, through animal behavior analyses, positron emission tomography (PET) imaging, and neuronal morphological analyses, we explored the role of KMT2E haploinsufficiency in ASD-like symptoms. Behavioral results revealed that KMT2E haploinsufficiency was sufficient to produce social deficit, accompanied by anxiety in mice. Whole-brain 18F-FDG-PET analysis identified that relative amygdala glycometabolism was selectively decreased in KMT2E+/− mice compared to wild-type mice. The numbers and soma sizes of amygdala neurons in KMT2E+/− mice were prominently increased. Additionally, KMT2E mRNA levels in human amygdala were significantly decreased after birth during brain development. Our findings support a causative role of KMT2E in ASD development and suggest that amygdala neuronal development abnormality is likely a major underlying mechanism. [ABSTRACT FROM AUTHOR]

Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes. [ABSTRACT FROM AUTHOR]

Purpose: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. Methods: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. Results: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78–1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82–1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). Conclusion: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light. [ABSTRACT FROM AUTHOR]

A deep foundation pit constructed in unsaturated soils had encountered torrential rainfall during excavation, and measurements indicated an unexpected excavation deformation caused by the rainfall. In view of this issue, a three-dimensional numerical model was developed, considering the hydro-mechanical coupling effect together with the variation in the hydraulic properties of unsaturated soils. The feasibility of the numerical model was validated by field data. Based on the results of the developed model, the responses of the retaining structure deformations, earth pressures on the retaining structure and pore-water structure were discussed in detail. Moreover, the stress paths of several points inside and outside the pit were analyzed to reveal the combined effect of rainfall and excavation. It was found that: (1) the excessive deformation of the foundation pit was closely correlated to the combined effect of rainfall and excavation; (2) such responses could be attributed to the variation in pore-water pressure, as well as the effective stress induced by rainfall and excavation; (3) the post-rainfall excavation was the key factor in further deformation aggravation in the foundation pit. [ABSTRACT FROM AUTHOR]

Benggang erosion is caused by a special type of gully erosion in southern China that seriously endangers the local ecology and environment. In this study, typical Benggang collapsing-wall soils were used as the study area to investigate the effects of different initial moisture contents and dicranopteris linearis root weight densities, as well as their interactions on disintegration in orthogonal test method. The results showed that the rate of soil disintegration decreased as a linear function of the initial moisture content. The soil disintegration rate tended to rise and then fall as the root weight density increased, reflecting an optimum root weight density of 0.75–1.00 g/100 cm3. The incorporation of dicranopteris linearis roots was most effective for soil consolidation in the shallow layers of soil. In addition, the disintegration rate of the collapsing-wall soils increases as the soil layer deepened. The dicranopteris linearis root system and initial moisture content had an interactive effect that was more pronounced in deeper soils. However, the combined effect of these processes was always dominated by the initial moisture content. Moderate initial soil moisture content (0.20–0.24 g/g) and the addition of a high root density in dicranopteris linearis (0.75–1.00 g/100 cm3) were the optimal combinations that reduced the disintegration rate. In conclusion, maintaining a suitable natural moisture content in collapsing-wall soils and taking measures that use plants to consolidate soil can effectively prevent and control the occurrence of Benggang erosion. The results of this study provided further insight into the factors that influence soil disintegration and offered a scientific basis for soil erosion management in the southern China. [ABSTRACT FROM AUTHOR]

Objectives: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. Methods: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. Results: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. Conclusion: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. Key Points: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the relation between topological pressure of free semigroup actions for non-compact sets proposed by Xiao and Ma (J Dynam Differ Equ, 2021) and measure-theoretic pressure of Borel probability measure. For any Borel probability measure, this paper defines lower and upper measure-theoretic pressures. Moreover, we give a lower and an upper estimations of the topological pressure of free semigroup actions by local measure-theoretic pressure. In addition, we also show that the topological pressure on a non-empty compact subset K defined in Xiao and Ma (J Dynam Differ Equ, 2021) equals to the supremum of the lower measure-theoretic pressure taken over all probability measures supported on K. [ABSTRACT FROM AUTHOR]

Diaryliodonium salts have been extensively applied in organic synthesis as aryl cation equivalents. However, in the electrophilic reactions with alkenes or alkynes, only the electrophilic carbon of the diaryliodonium salts was involved while the other part of the aryl ring was not utilized. Herein, a reaction pattern of diaryliodonium was reported as oxa-1,4-dipoles to undergo (4 + 2) cycloaddition reactions with alkynes. Broad spectrum of the two reaction partners could be utilized in this protocol, enabling an operationally simple, high yielding, and regioselective synthetic approach to isocoumarins. Particularly, good to excellent regioselectivities were achieved for the sterically unbiased unsymmetrical diaryl acetylenes, which was challenging for other transition metal-catalyzed processes. The reaction could be scaled up with the ideal 1:1 stoichiometry and the isocoumarin type natural products Oospolactone and Thunberginol A could be obtained in one or three steps through this methodology. Intermolecular (4 + 2) cycloaddition with alkynes is a powerful approach to construct isocoumarin moieties, however, regioselectivity remains challenging for the transition metal-catalyzed approach. Here, the authors report copper-catalyzed regioselective (4 + 2) annulations between diaryliodonium salts and alkynes to synthesize isocoumarin-type natural products. [ABSTRACT FROM AUTHOR]

Objectives: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery.Methods: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method.Results: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy.Conclusion: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients.Key Points: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts. [ABSTRACT FROM AUTHOR]

The Qinghai-Tibet Plateau (QTP), possesses a climate as cold as that of the Arctic, and also presents uniquely low oxygen concentrations and intense ultraviolet (UV) radiation. QTP animals have adapted to these extreme conditions, but whether they obtained genetic variations from the Arctic during cold adaptation, and how genomic mutations in non-coding regions regulate gene expression under hypoxia and intense UV environment, remain largely unknown. Here, we assemble a high-quality saker falcon genome and resequence populations across Eurasia. We identify female-biased hybridization with Arctic gyrfalcons in the last glacial maximum, that endowed eastern sakers with alleles conveying larger body size and changes in fat metabolism, predisposing their QTP cold adaptation. We discover that QTP hypoxia and UV adaptations mainly involve independent changes in non-coding genomic variants. Our study highlights key roles of gene flow from Arctic relatives during QTP hypothermia adaptation, and cis-regulatory elements during hypoxic response and UV protection. The Qinghai-Tibet Plateau is as cold as the Arctic, but presents unique hypoxia and high ultraviolet conditions. Here the authors find that gene flow from Arctic gyrfalcons aids plateau saker falcons' cold adaptation, and independent non-coding genomic changes underlie hypoxic and ultraviolet responses. [ABSTRACT FROM AUTHOR]

Obesity and asthma are both common diseases with high population burden worldwide. Recent genetic association studies have shown that obesity is associated with asthma in adults. The relationship between childhood obesity and childhood asthma, and the underlying mechanisms linking obesity to asthma remain to be clarified. In the present study, leveraging large-scale genetic data from UK biobank and several other data sources, we investigated the shared genetic components between body mass index (BMI, n = 39620) in children and childhood asthma (ncase = 10524, ncontrol = 373393). We included GWAS summary statistics for nine obesity-related biomarkers to evaluate potential biological mediators underlying obesity and asthma. We found a genetic correlation (Rg = 0.10, P = 0.02) between childhood BMI and childhood asthma, whereas the genetic correlation between adult BMI (n = 371541) and childhood asthma was null (Rg = −0.03, P = 0.21). Genomic structural equation modeling analysis further provided evidence that the genetic effect of childhood BMI on childhood asthma (standardized effect size 0.17, P = 0.009) was not driven by the genetic component of adult BMI. Bayesian colocalization analysis identified a shared causal variant rs12436181 that was mapped to gene AMN using gene expression data in lung tissue. Mendelian randomization showed that the odds ratio of childhood asthma for one standard deviation higher of childhood BMI was 1.13 (95% confidence interval: 0.96–1.34). A systematic survey of obesity-related biomarkers showed that IL-6 and adiponectin are potential biological mediators linking obesity and asthma in children. This large-scale genetic study provides evidence that unique childhood obesity pathways could lead to childhood asthma. The findings shed light on childhood asthma pathogenic mechanisms and prevention. A comprehensive genetic analysis of the relationship between childhood obesity and childhood asthma identifies shared mechanisms and potential mediators linking the two pediatric disorders. [ABSTRACT FROM AUTHOR]

The long-term application of chemical fertilizers has caused to the farmland soil compaction, water pollution, and reduced the quality of vegetable to some extent. So, its become a trend in agriculture to find new bio-fertilizers. Chlorella extract is rich in amino acids, peptides, nucleic acids, growth hormones, potassium, calcium, magnesium, iron, zinc ions, vitamin E, B1, B2, C, B6, folic acid, free biotin and chlorophyll. Chlorella extract can promote biological growth, mainly by stimulating the speed of cell division, thereby accelerating the proliferation rate of cells and playing a role in promoting plant growth. Whether Chlorella extract can be used to improve the growth of pepper (Capsicum annuum), needs to be verified. In current study, a pepper variety 'Chao Tian Jiao' was used as experiment material, by determining the changes of the related characteristics after spraying the seedlings with Chlorella extract, and its effect on growth of Capsicum annuum plants was investigated. The results showed that the Chlorella extract significantly increased plant height of pepper seedlings (treatment: 32.2 ± 0.3 cm; control: 24.2 ± 0.2 cm), stem diameter (treatment: 0.57 ± 0.02 cm; control: 0.41 ± 0.03 cm) and leaf area (treatment: 189.6 ± 3.2 cm2; control: 145.8 ± 2.5 cm2). Particularly, the pepper seedlings treated with Chlorella extract, developed the root system in better way, significantly increased the chlorophyll a, and the activities of SOD, POD and CAT enzymes were also improved significantly. Based on our results, we can speculate that it is possible to improve the growth of Capsicum annuum seedlings and reduce the application of chemical fertilizers in pepper production by using Chlorella extract. [ABSTRACT FROM AUTHOR]